Phase III Trial of Anlotinib, Catequentinib in Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma, Synovial Sarcoma (APROMISS)
- Conditions
- Alveolar Soft Part SarcomaSynovial SarcomaSoft-Tissue SarcomaLeiomyosarcoma
- Interventions
- Registration Number
- NCT03016819
- Lead Sponsor
- Advenchen Laboratories, LLC
- Brief 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.
- Detailed Description
THIS STUDY IS CURRENTLY RECRUITING PATIENTS WITH ALVEOLAR SOFT PART SARCOMA ONLY AND IS NO LONGER RECRUITING PATIENTS WITH SYNOVIAL SARCOMA OR LEIOMYOSARCOMA.
APROMISS is a phase 3 study evaluating 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). Population pharmacokinetics and exploratory exposure-response analyses will also be conducted in subjects receiving AL3818.
Indication A: 56 subjects with metastatic or advanced ASPS not amenable to surgical resection will receive open-label AL3818 at a dose of 12 mg once daily in 21-day cycles (14 days on treatment, 7 days off treatment) until disease progression (defined by RECIST version 1.1) ot unacceptable toxicity. The primary endpoint is objective response rate (ORR), secondary endpoint is duration of response (DOR). - CLOSED
Indication B: 68 subjects with metastatic or advanced LMS who have failed at least one prior line of approved therapy will be enrolled and randomized in a 2:1 ratio to receive either AL3818 (12 mg once daily in 21-day cycles) or IV dacarbazine until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to dacarbazine will have the option to crossover and receive AL3818 at the time of documented disease progression. The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR). - CLOSED
Indication C: 95 subjects with with metastatic or advanced SS who have failed at least one prior line of approved therapy, including first-line anthracycline-containing chemotherapy, will be enrolled and randomized in a 2:1 ratio to receive either AL3818 (12 mg once daily in 21-day cycles) or IV dacarbazine until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to dacarbazine will have the option to crossover and receive AL3818 at the time of documented disease progression. The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR). - CLOSED
Indication D - LMS: 106 subjects with histologically proven, unresectable, recurrent, locally advanced or metastatic leiomyosarcoma (of soft tissue, cutaneous origin, and vascular origin who have failed at least one prior line of standard therapy (including anthracycline-based therapy) and are ineligible for or refuse standard second-line therapy or are suitable for third- and further-line treatment will be enrolled. Subjects will be randomized with a 2:1 ratio to receive either blinded AL3818 or placebo with approximately 71 subjects in the AL3818 group and 35 subjects in the placebo group until disease progression (defined by RECIST version 1.1) or unacceptable toxicity. Subjects randomized to placebo will have the option to crossover and receive AL3818 at the time of documented disease progression (and after crossover unblinding). The primary endpoint is progression free survival (PFS), the secondary endpoint is objective response rate (ORR). - CLOSED
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 325
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Indication D: LMS AL3818 or Placebo Arm - CLOSED AL3818 or placebo 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). Indication A: ASPS AL3818 Arm - CLOSED AL3818 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). Indication B: LMS AL3818 Arm - CLOSED AL3818 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). Indication B: LMS Dacarbazine Arm - CLOSED Dacarbazine 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. Indication C: SS AL3818 Arm - CLOSED Dacarbazine 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). Indication C: SS Dacarbazine Arm - CLOSED Dacarbazine 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.
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) (LMS/SS) From time of randomization to the date of disease progression or death from any cause, up to 48 months To compare PFS in subjects with LMS or SS randomized to AL3818 versus dacarbazine, defined a median number of months from the date of randomization until the first documented sign of disease progression or death due to any causes, whichever occurs earlier as evaluated by a blinded independent radiologic review (BICR).
Objective Response Rate (ORR) (ASPS) Up to 48 months To determine ORR in subjects with ASPS, defined as percentage of subjects who achieve a Complete Response (CR) or Partial Response (PR) as best responses according to RECIST 1.1 as evaluated by a blinded independent radiological review (BICR).
- Secondary Outcome Measures
Name Time Method Duration of Response (DOR) (ASPS) Up to 48 months To determine DOR in subjects with ASPS, defined as median number of months from date of first documented objective response until first documented sign of disease progression or death due to any causes
Objective Response Rate (ORR) (LMS/SS) Up to 48 months To compare ORR in subjects with LMS or SS randomized to AL3818 versus dacarbazine, defined as percentage of subjects who achieve a Complete Response (CR) or Partial Response (PR) as best responses according to RECIST 1.1 as evaluated by a blinded independent radiological review (BICR).
Trial Locations
- Locations (23)
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Thomas Jefferson Hospital - Sidney Kimmel Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
UW Medicine-Seattle Cancer Care Alliance
🇺🇸Seattle, Washington, United States
Istituto Nazionale dei Tumori
🇮🇹Milano, Italy
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Vanderbilt University
🇺🇸Nashville, Tennessee, United States
Mayo Clinic Arizona
🇺🇸Phoenix, Arizona, United States
Mayo Clinic Rochester
🇺🇸Rochester, Minnesota, United States
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Stanford Medicine Cancer Institute
🇺🇸Stanford, California, United States
Sarcoma Oncology Center
🇺🇸Santa Monica, California, United States
Mayo Clinic Jacksonville
🇺🇸Jacksonville, Florida, United States
University of Michigan Comprehensive Cancer Center
🇺🇸Ann Arbor, Michigan, United States
Washington University St. Louis
🇺🇸Saint Louis, Missouri, United States
Beijing Cancer Hospital
🇨🇳Beijing, China
Shanghai Sixth People's Hospital
🇨🇳Shanghai, China
University of Palermo
🇮🇹Palermo, Italy
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
University Campus Bio-Medico
🇮🇹Rome, Italy
Royal Marsden Hospital
🇬🇧London, United Kingdom