This is an open label neoadjuvant (treatment with VS-6063 prior to mesothelioma surgery) study in subjects with malignant pleural mesothelioma who are eligible for surgery. Subjects will receive VS-6063 (defactinib) 400 mg twice daily for 12, 21, or 35 days or 100 mg formulation twice daily for 21 days. Pre- and post-treatment biopsies and blood samples will be collected. The purpose of this study is to assess biomarker responses from tumor tissue. The safety, pharmacokinetics, and tumor response rate to VS-6063 (defactinib) will be also be assessed.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
35
Brigham and Women's Hospital
Boston, Massachusetts, United States
Percentage of pFAK Inhibition in Tumor Tissue
percentage VS-6063 (defactinib)
Time frame: Cohort 1, From Baseline to Day 12; Cohort 2, From Baseline to Day 35; Cohorts 3, From Baseline to Day 21; Cohorts 3, From Baseline to day 21 day.
Evaluate the Pharmacokinetics of VS-6063 (Defactinib), CMax
Maximum observed plasma concentration
Time frame: 0-24 hours
Evaluate the Pharmacokinetics of VS-6063 (Defactinib), AUC (Area Under the Curve)
Area under plasma Concentration (AUC) 0 to t
Time frame: 0-8 hours
Evaluate the Pharmacokinetics of VS-6063 (Defactinib), Median Tmax (h)
Time to Maximum concentration (Tmax)
Time frame: 0-24 hours
Number of Patients With at Least One Adverse Event
Adverse events will be graded by the CTCAE (Common Terminology Criteria for Adverse Events) 4.0 and summarized according to the worst grade observed since the first treatment dose.
Time frame: Cohort 1, 40 days; Cohort 2, 42 days; Cohort 3, 28 days; Cohort 4, 28 days.
To Evaluate the Tumor Response to VS-6063 (Defactinib)
Modified RECIST criteria for assessment of response in malignant pleural mesothelioma Ann Oncol 2004. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the in the volume of target lesions; Progressive Disease (PD) at least a 20% increase in the volume of target lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter.
Time frame: Cohort 1, 40 days; Cohort 2, 42 days; Cohort 3, 28 days; Cohort 4, 28 days.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.