This study is a Phase 2, randomized, double-blind, placebo-controlled, multicenter study of defactinib (VS-6063) in subjects with malignant pleural mesothelioma (MPM) who have not progressed (confirmed partial response or stable disease) following ≥ 4 cycles of treatment with pemetrexed/cisplatin or pemetrexed/carboplatin. Prior to entry and randomization to the study, each subject must have tumor Merlin status(high or low) established by immunohistochemistry performed at a central laboratory. Subjects will be randomized in a 1:1 ratio to receive oral VS-6063 400 mg twice per day, or matched placebo. Randomization will be stratified by tumor Merlin status (high versus low). Progression will be assessed both locally and by central review using the Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1. Subjects will continue to receive treatment until disease progression or other discontinuation criteria are met. Following documentation of nonfatal disease progression, all subjects will be followed for overall survival by telephone contact every 2 months until end of life or the close of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
344
Sugar pill manufactured to mimic defactinib tablet
University of California San Francisco Medical Center
San Francisco, California, United States
Cleveland Clinic Florida
Weston, Florida, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Mayo Clinic
Rochester, Minnesota, United States
Compare the overall survival (OS) in subjects with malignant pleural mesothelioma receiving defactinib (VS-6063) or placebo
The median duration of OS will be estimated based on the 50th percentile of the Kaplan-Meier distribution
Time frame: From randomization to end of life, an expected average of 12 months
Compare the progression free survival (PFS) in subjects with malignant pleural mesothelioma receiving defactinib (VS-6063) or placebo
PFS will be calculated based on the stratified log-rank test, and will use Kaplan-Meier estimation methods for estimation of summary statistics
Time frame: From date of randomization to earliest documented date of progression, an expected average of 4 months
To assess Quality of Life (QoL) in subjects treated with defactinib (VS-6063) or placebo using the Lung Cancer Symptom Scale modified for mesothelioma (LCSS-Meso)
QoL will be assessed using the LCSS-Meso. The LCSS-Meso total score will be analyzed through a comparison of median area under the curve (AUC) between the 2 treatment groups using a Wilcoxon test.
Time frame: Every 3-4 weeks from baseline through end of treatment, an expected average of 4 months
To determine the objective response rate (ORR) in subjects receiving defactinib (VS-6063) or placebo.
ORR is measured as the best overall response assessed by central review using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.
Time frame: Every 6-8 weeks from baseline through end of treatment, an expected average of 4 months
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Roswell Park Cancer Institute
Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Jacobi Medical Center
The Bronx, New York, United States
Cleveland Clinic
Cleveland, Ohio, United States
Abramson Cancer Center
Philadelphia, Pennsylvania, United States
...and 63 more locations