Window of Opportunity Study of VS-6063 (Defactinib) in Surgical Resectable Malignant Pleural Mesothelioma Participants

Phase 2

Terminated

Conditions: Malignant Pleural Mesothelioma

Interventions: Drug: VS-6063

Registration Number: NCT02004028

Lead Sponsor: Verastem, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 35

Inclusion Criteria

Histologically confirmed malignant pleural mesothelioma that is not metastatic or unresectable
Eligible to undergo excisional surgery such as pleurectomy/decortication (P/DC) or any other mesothelioma surgery.
Localized disease. The malignancy is confined to one affected hemithorax. Mediastinal N2 lymph nodes via cervical mediastinoscopy or EBUS (endobronchial ultrasound) must be negative in order to be eligible
Grossly normal pulmonary, cardiac function, renal, hepatic hematologic and performance functions
Male or non-pregnant female
Age ≥ 18 years of age
Tissue is required prior to enrollment. If patient was diagnosed outside and tumor tissue is not available, a pleural biopsy for frozen tissue collection is required.

Exclusion Criteria

Participants who have had chemotherapy or radiotherapy any time prior to entering the study or at any prior time for mesothelioma. Patients receiving chemotherapy type drugs for benign conditions can participate in this trial
History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug
Known history of Gilbert's Syndrome or any current hyperbilirubinemia of any cause
Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug
Subjects with known infection with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS)
Subjects with confirmed Hepatitis A, B or C
Subjects being actively treated for a secondary malignancy or any malignancy within the last 3 years, with the exception of non-melanomatous skin cancer or localized, definitively treated cervical cancer. Men under observation for local prostate cancer are also eligible if they have had stable disease for at least 1 year.
Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis
Known history of malignant hypertension
Uncontrolled intercurrent illness including symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations which in the opinion of the study investigators would be associated with undue risk of participation in the study
Use of an investigational drug within 28 days or 5 half-lives prior to first dose.
Pregnant or breastfeeding

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
VS-6063 (defactinib)	VS-6063	Administered orally (BID) for 12, 21 or 35 days (+/- 2 days)

Primary Outcome Measures

Name	Time	Method
Percentage of pFAK Inhibition in Tumor Tissue	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.	percentage VS-6063 (defactinib)
Evaluate the Pharmacokinetics of VS-6063 (Defactinib), CMax	0-24 hours	Maximum observed plasma concentration
Evaluate the Pharmacokinetics of VS-6063 (Defactinib), AUC (Area Under the Curve)	0-8 hours	Area under plasma Concentration (AUC) 0 to t
Evaluate the Pharmacokinetics of VS-6063 (Defactinib), Median Tmax (h)	0-24 hours	Time to Maximum concentration (Tmax)

Secondary Outcome Measures

Name	Time	Method
Number of Patients With at Least One Adverse Event	Cohort 1, 40 days; Cohort 2, 42 days; Cohort 3, 28 days; Cohort 4, 28 days.	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.
To Evaluate the Tumor Response to VS-6063 (Defactinib)	Cohort 1, 40 days; Cohort 2, 42 days; Cohort 3, 28 days; Cohort 4, 28 days.	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.

Trial Locations

Locations (1): Brigham and Women's Hospital
🇺🇸
Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States