Auto-populated list of related Clinical Trials
(Breast, Cleft Lip and Palate, Hand, Lymphedema, Oral, Skin, Trauma)

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting

A Phase III Trial of Anlotinib in Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

This study evaluates the safety and efficacy of AL3818 (anlotinib) hydrochloride in the treatment of metastatic or advanced alveolar soft part sarcoma (ASPS), leiomyosarcoma (LMS), and synovial sarcoma (SS). All participants with ASPS will receive open-label AL3818. In participants with LMS or SS, AL3818 will be compared to IV dacarbazine. Two-thirds of the participants will receive AL3818, one-third of the participants will receive IV dacarbazine.

Stanford is currently accepting patients for this trial.

Lead Sponsor:

Advenchen Laboratories, LLC

Stanford Investigator(s):

Intervention(s):

  • Drug: AL 3818
  • Drug: Dacarbazine

Phase:

Phase 3

Eligibility


Inclusion Criteria:

   1. Written informed consent provided before any study-specific procedures are initiated.
   Subject must be able to understand and be willing to sign a written informed consent
   form.

   2. Male or female at least 18 years of age.

   3. Indication A - ASPS: Histologically proven, unresectable, locally advanced or
   metastatic alveolar soft part sarcoma.

      - Indication B - LMS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular
      origin and of the bone).

      - Indication C - SS: Histologically proven, unresectable, recurrent, locally
      advanced or metastatic synovial sarcoma.

   4. Indication A - ASPS: Subjects with no prior therapy or subjects with prior treatment
   with chemotherapy or an angiogenesis inhibitor (e.g., sunitinib).

      - Indications B - LMS: Subjects previously treated with at least one prior line of
      approved therapy.

      - Indication C - SS: Subjects previously treated with at least one prior line of
      approved therapy, including first-line anthracycline containing regimen.

   5. Show objective disease progression after the last administration of the last standard
   therapy or have stopped standard therapy due to intolerability (excluding ASPS
   subjects who have not received prior therapy) within 6 months of enrollment.

   6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

   7. Has measurable disease according to Response Evaluation Criteria in Solid Tumors
   (RECIST) version 1.1 confirmed by CT or MRI scan within 28 days prior to enrollment.

   8. Life expectancy of at least 3 months.

   9. Females of childbearing potential must have a negative pregnancy test (by serum
   beta-HCG) within 7 days prior to the start of treatment.

10. Female of childbearing potential must be surgically sterile (have had a hysterectomy
   or bilateral oophorectomy, tubal ligation), abstinent (at the discretion of the
   investigator), or agree to use adequate contraception since signing of the informed
   consent form until at least 3 months after the last study drug administration. Females
   of childbearing potential are those who have not been surgically sterilized or have
   not been free from menses for > 2 years. - Males must agree to use adequate
   contraception since signing of the informed consent form until at least 3 months after
   the last study drug administration. Adequate contraception is defined in the study as
   any medically recommended method (or combination of methods) at the discretion of the
   investigator.

11. Adequate hematologic, hepatic and renal function as assessed by the following
   laboratory requirements conducted within 7 days of starting study treatment:

      - Total bilirubin < the upper limit of normal (ULN)

      - Alanine aminotransferase and aspartate aminotransferase < 2.5 of the ULN (< 5 x
      of ULN for subjects with liver involvement of their cancer)

      - Amylase and lipase < 1.5 x of ULN

      - Serum creatinine < 1.5 x of ULN

      - Glomerular filtration rate > 30ml/min/1.73 m2 according to the Modified Diet in
      Renal Disease abbreviated formula or creatinine clearance (CrCL) > 60 ml/min
      (Cockcroft and Gault)

      - International normalize ratio (INR) and the partial thromboplastin time (PTT) <
      1.5 x ULN. (Subjects who are therapeutically treated with an agent such as
      warfarin or heparin will be allowed to participate provided that no prior
      evidence of an underlying abnormality in coagulation parameters exists)

      - Platelet count > 100,000 cells/mm3, hemoglobin > 9 g/dL, absolute neutrophil
      count > 1,500 cells/mm3

      - Alkaline phosphatase limit <2.5 x ULN (<5 x ULN for subjects with liver
      involvement of their cancer)

      - Spot urine must not show 1+ or more protein in urine or the subject will require
      a repeat urinalysis. If repeat urinalysis shows 1+ protein or more, a 24-hour
      urine collection will be required and must show total protein excretion <1,000 mg
      per 24 hours.

12. Left ventricular ejection fraction (LVEF) of > 50% by Doppler ultrasound assessment

Exclusion Criteria:

   1. Prior treatment with or have known hypersensitivity to AL3818.

   2. a. Indication A - ASPS: Prior treatment with cediranib.

      - b. Indication B- LMS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

      - c. Indication C - SS: Prior treatment with or have known hypersensitivity to
      dacarbazine.

   3. Previous or concurrent cancer that is distinct in primary site or histology from ASPS,
   LS, or SS within 5 years before enrollment except for curatively treated cervical
   cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta, Tis and
   T1).

   4. Received last dose of systemic cytotoxic therapy, radiation therapy or therapy with
   any investigational product within 28 days of enrollment.

   5. Prior treatment with extended-field radiotherapy within 28 days prior to enrollment or
   prior treatment with extended-field radiotherapy for evaluating tumor lesions within
   14 days prior to enrollment.

   6. Known active CNS metastases and/or carcinomatous meningitis. Patients with previously
   treated brain metastases may participate provided that they are stable with no
   evidence of progression by imaging, and all neurologic symptoms have returned to
   baseline, and should not be using corticosteroids for at least 7 days prior to study
   treatment.

   7. Cavitary tumors or tumors invading or abutting large blood vessels.

   8. History of gastrointestinal perforation, abdominal fistula or intra-abdominal abscess
   within 6 months of enrollment.

   9. Known history of bleeding disorders (e.g., von Willebrand disease or hemophilia).

10. Clinically significant bleeding such as gross hematuria, gastrointestinal bleeding and
   hemoptysis within 6 months prior to enrollment.

11. CTCAE version 4.03 > grade 2 pulmonary hemorrhage or > grade 3 of other forms of
   bleeding within 28 days prior to enrollment.

12. Thromboembolic events (e.g., deep vein thrombosis, pulmonary embolism, arterial
   thrombosis) within 6 months prior to enrollment.

13. Use of aspirin (>325 mg/day) within 10 days prior to the first dose of study
   treatment. The use of prophylactic therapeutic anti-coagulants are allowed provided
   that INR or aPTT are within therapeutic limits (according to the medical standard of
   the enrollment institution) and patient has been on a stable dose of anticoagulants
   for at least two weeks prior to the first dose of study treatment.

14. Serious non-healing wound, active ulcer, or unhealed bone fracture.

15. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
   prior to enrollment.

16. CTCAE version 4.03 > grade 3 peripheral neuropathy

17. Any unrecovered toxicity reactions of CTCAE version 4.03 > grade 1 caused by any
   previous therapy (excluding alopecia and neurotoxicity < grade 2)

18. QTc > 470 msec on electrocardiogram

19. Severe and uncontrolled disease, including:

      - a. Class I and above myocardial ischemia or myocardial infarction, cardiac
      arrhythmia and Class 2 or above congestive heart failure classified according to
      New York Heart Association (NYHA)

      - b. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic
      blood pressure > 90 mmHg despite optimal medical management)

      - c. Active or failed to control serious infections (CTCAE version 4.03 > grade 2
      infections)

      - d. Liver disease such as cirrhosis of the liver, decompensated liver disease,
      chronic active hepatitis needing anti-viral therapy

      - e. Renal failure needing hemodialysis or peritoneal dialysis

      - f. Poorly controlled diabetes (fasting blood glucose > 180 mg/dL)

      - g. Untreated and uncontrolled epileptic seizures

      - h. History of psychotropic drug abuse and inability to quit

      - i. Untreated psychiatric disorders

20. Known HIV-positive

21. Had organ transplantation

22. Clinical conditions affecting the intake and use of oral medications (e.g., inability
   to swallow, chronic diarrhea, and intestinal obstruction)

23. Females who are pregnant or are breast-feeding.

24. Concomitant treatment with strong inhibitors or inducers of CYP1A2, CYP3A4 or CYP3A5
   or sensitive substrates with narrow therapeutic index (TI) of CYP3A4, CYP2C9 and
   CYP2C19 within 14 days prior to enrollment and during the study unless there was an
   emergent or life-threatening medical condition that required it.

25. Any medical intervention, condition or any other circumstance which in the opinion of
   the investigator or the sponsor's medical monitor, could compromise adherence to study
   procedures or study objectives.

Ages Eligible for Study

18 Years - N/A

Genders Eligible for Study

All

Now accepting new patients

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Feriel Buchholz
650-721-4090
Recruiting