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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

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

Brief Summary: 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 Summary:

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: 53 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).

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 endpoints are objective response rate (ORR) and overall survival (OS).

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 o
Sponsor: Advenchen Laboratories, LLC

Current Primary Outcome:

• Objective Response Rate (ORR) (ASPS) [ Time Frame: 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).
• Progression Free Survival (PFS) (LMS/SS) [ Time Frame: 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).

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Duration of Response (DOR) (ASPS) [ Time Frame: 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) [ Time Frame: 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).
• Overall Survival (OS) (LMS/SS) [ Time Frame: From time of randomization to the of death from any cause, up to 48 months ]
  To compare OS in subjects with LMS or SS randomized to AL3818 versus dacarbazine, defined as the time from the date of randomization to date of death from any cause.

Original Secondary Outcome:

• Duration of Response (DOR) (ASPS) [ Time Frame: 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) [ Time Frame: 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).
• Overall Survival (OS) (LMS/SS) [ Time Frame: From time of randomization to the of death from any cause, up to 5 years ]
  To compare OS in subjects with LMS or SS randomized to AL3818 versus dacarbazine, defined as the time from the date of randomization to date of death from any cause.

Information By: Advenchen Laboratories, LLC

Dates:
Date Received: January 6, 2017
Date Started: April 2017
Date Completion: August 2021
Last Updated: January 26, 2017
Last Verified: January 2017