A Phase III Study of AL3818 (Anlotinib, Catequentinib) Hydrochloride Monotherapy in Subjects With Metastatic or Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma and Synovial Sarcoma

Who is this study for? Adult patients with Locally Advanced or Metastatic Alveolar Soft Part Sarcoma
Status: Active, not recruiting
Location: See all (23) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 3
SUMMARY

THIS STUDY IS CURRENTLY RECRUITING PATIENTS WITH ALVEOLAR SOFT PART SARCOMA ONLY AND IS NO LONGER RECRUITING PATIENTS WITH SYNOVIAL SARCOMA OR LEIOMYOSARCOMA. 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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: No
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• 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.

• Male or female at least 18 years of age.

• a. Indication A - ASPS: Histologically proven, unresectable, locally advanced or metastatic alveolar soft part sarcoma. b. CLOSED Indication B - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, vascular origin and of the bone). c. CLOSED Indication C - SS: Histologically proven, unresectable, recurrent, locally advanced or metastatic synovial sarcoma. d. CLOSED Indication D - LMS: Histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, and vascular origin).

• a. Indication A - ASPS: Subjects with or without prior therapy. b. Indications B - LMS: Subjects previously treated with at least one prior line of approved therapy. (New Recruitment Suspended) c. Indication C - SS: Subjects previously treated with at least one prior line of standard systemic therapy, including first-line anthracycline containing regimen (except if medically contraindicated or refused by subject). d. Indication D - LMS: Treatment of patients with metastatic or advanced leiomyosarcoma (LMS) who have failed at least one prior line of standard therapy and are ineligible for or refuse standard second-line therapy or are suitable for third- and further-line treatment. Patients must have received and progressed on prior therapy and have been treated any line with an anthracycline.

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

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

• Has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by CT or MRI scan of the chest, abdomen and pelvis (and other areas of disease) within 28 days prior to enrollment.

• Life expectancy of at least 3 months.

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

• 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.

• Adequate hematologic, hepatic and renal function as assessed by the following laboratory requirements conducted within 28 days of enrollment:

• Total bilirubin < the upper limit of normal (ULN), unless the patient has documented Gilbert's disease for which the total bilirubin should be < 3.

• 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) or by 24 hour urine collection.

• International normalize ratio (INR) and the activated partial thromboplastin time (aPTT/PTT) < 1.5 x ULN. (Subjects who are therapeutically treated with an agent such LMWH 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)

• Urine protein < 30 mg/dL. If urine protein is > 30 mg/dL, a 24-hour urine collection will be required and must show total protein excretion <1,000 mg per 24 hours or spot urine protein (mg/dL) to creatinine (mg/dL) ratio must be <1.0.

• Left ventricular ejection fraction (LVEF) of > 50% by ECHO or MUGA within 56 days of enrollment.

• Two readings of systolic blood pressure < 140 mm Hg and diastolic blood pressure < 90 mm Hg at screening taken at least 5 minutes apart in the sitting position after 5 minutes of rest. Subjects with well managed hypertension who are on oral antihypertensives must be on their current medication(s) and stable dose(s) for at least 2 weeks prior to enrollment.

Locations
United States
Arizona
Mayo Clinic Arizona
Phoenix
California
University of California Los Angeles
Los Angeles
Sarcoma Oncology Center
Santa Monica
Stanford Medicine Cancer Institute
Stanford
Colorado
University of Colorado Denver
Aurora
Florida
Mayo Clinic Jacksonville
Jacksonville
University of Miami Sylvester Comprehensive Cancer Center
Miami
Illinois
Northwestern University
Chicago
Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor
Minnesota
Mayo Clinic Rochester
Rochester
Missouri
Washington University St. Louis
Saint Louis
Pennsylvania
Thomas Jefferson Hospital - Sidney Kimmel Cancer Center
Philadelphia
University of Pittsburgh Medical Center
Pittsburgh
Tennessee
Vanderbilt University
Nashville
Texas
MD Anderson Cancer Center
Houston
Washington
UW Medicine-Seattle Cancer Care Alliance
Seattle
Other Locations
China
Beijing Cancer Hospital
Beijing
Shanghai Sixth People's Hospital
Shanghai
Italy
Istituto Nazionale dei Tumori
Milano
University of Palermo
Palermo
University Campus Bio-Medico
Rome
Spain
Hospital de la Santa Creu i Sant Pau
Barcelona
United Kingdom
Royal Marsden Hospital
London
Time Frame
Start Date: August 15, 2017
Estimated Completion Date: April 2023
Participants
Target number of participants: 325
Treatments
Experimental: Indication A: ASPS AL3818 Arm - CLOSED
All subjects with ASPS will be assigned to the open-label AL3818 arm to receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).
Experimental: Indication B: LMS AL3818 Arm - CLOSED
Subjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to AL3818 will receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).
Active Comparator: Indication B: LMS Dacarbazine Arm - CLOSED
Subjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to IV dacarbazine will receive dacarbazine at a dose of 1000 mg/m^2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle.
Experimental: Indication C: SS AL3818 Arm - CLOSED
Subjects with SS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to AL3818 will receive 12 mg AL3818 capsules orally once daily in 21-day cycles (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).
Active Comparator: Indication C: SS Dacarbazine Arm - CLOSED
Subjects with SS will be randomized in a 2:1 ratio to receive either AL3818 or IV dacarbazine. Subjects randomized to IV dacarbazine will receive dacarbazine at a dose of 1000 mg/m^2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle.
Placebo Comparator: Indication D: LMS AL3818 or Placebo Arm - CLOSED
Subjects with LMS will be randomized in a 2:1 ratio to receive either AL3818 or placebo in a double-blind manner. AL3818 or placebo will be administrated as one 12 mg capsule orally once daily in 21-day cycles for 14 days on treatment (Days 1-14) and 7 days off treatment (Days 15-21).
Sponsors
Leads: Advenchen Laboratories, LLC

This content was sourced from clinicaltrials.gov

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