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RecruitingNCT03016819

Phase III Trial of Anlotinib, Catequentinib in Advanced Alveolar Soft Part Sarcoma, Leiomyosarcoma, Synovial Sarcoma (APROMISS)

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

Status
Recruiting
Phase
Phase 3
Study type
Interventional
Enrollment
325 (estimated)
Sponsor
Advenchen Laboratories, LLC · Industry
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

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 In indication E-- A total sample size of 25 subjects will be enrolled to collect baseline PK and ECG data. A total of 18 patients are projected to complete collecting fourth cycle (C4) PK and ECG data. This C-QTc study will assess the potential for cardiac repolarization delays following administration of catequentinib hydrochloride. This assessment involves examination of the QT interval at the drug concentrations of baseline and fourth cycle of steady state which was concluded by population PK results. Catequentinib hydrochloride is a strong Cytochrome enzyme P450 3A4 (CYP3A4) inhibitor and mild inhibitor of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) based on the in vitro assay. This designed DDI study will assess how catequentinib hydrochloride affects the pharmacokinetics (PK) of midazolam (a known probe substrate of CYP3A4), Digoxin (a known probe substrate of P-gp) and rosuvastatin (a known probe substrate of BCRP) after the treatments of fourth cycles.

Conditions

Interventions

TypeNameDescription
DRUGAL3818Anlotinib (AL3818) 12 mg orally administered once daily in 21-day cycles (14 days on treatment, 7 days off treatment)
DRUGDacarbazineDacarbazine 1000 mg/m2 as a 20-120 minute IV infusion on Day 1 of each 21-day treatment cycle
DRUGAL3818 or placeboAL3818 or placebo 12 mg orally administered once daily in 21-day cycles (14 days on treatment, 7 days off treatment)
DRUGMidazolam 2 mg for CYP3A4 phenotypingIn indication E, midazolam will be used to see how catequentinib hydrochloride affects the pharmacokinetics (PK) of Cytochrome enzyme P450 3A4 (CYP3A4).
DRUGDigoxin (0.25mg)In indication E, Digoxin will be used to see how catequentinib hydrochloride affects the pharmacokinetics (PK) of P-glycoprotein.
DRUGRosuvastatin 10 mg tablet.In indication E, Rosuvastatin will be used to see how catequentinib hydrochloride affects the pharmacokinetics (PK) of breast cancer resistance protein .

Timeline

Start date
2017-08-15
Primary completion
2027-12-01
Completion
2028-12-01
First posted
2017-01-11
Last updated
2026-02-25

Locations

24 sites across 5 countries: United States, China, Italy, Spain, United Kingdom

Regulatory

Source: ClinicalTrials.gov record NCT03016819. Inclusion in this directory is not an endorsement.