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

Sponsor

Verastem, Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT02004028

Collaborator

(none)

Enrollment

Location

Arm

66.2

Actual Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Malignant Pleural Mesothelioma	Drug: VS-6063	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

35 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open Label Window of Opportunity Phase II Study of the FAK Inhibitor Defactinib VS-6063 in Participants With Surgical Resectable Malignant Pleural Mesothelioma.

Actual Study Start Date :

Dec 12, 2013

Actual Primary Completion Date :

Jun 19, 2019

Actual Study Completion Date :

Jun 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VS-6063 (defactinib) Administered orally (BID) for 12, 21 or 35 days (+/- 2 days)	Drug: VS-6063 Other Names: defactinib

Arm

Intervention/Treatment

Experimental: VS-6063 (defactinib)

Administered orally (BID) for 12, 21 or 35 days (+/- 2 days)

Drug: VS-6063

Other Names:

defactinib

Outcome Measures

Primary Outcome Measures

Assess biomarker responses to VS-6063 in tumor tissue [From Baseline to 12, 21 or 35 days (+/- 2 days) post-treatment]
To determine biomarker responses to the Focal Adhesion Kinase (FAK) inhibitor, VS-6063 (defactinib), in Malignant Pleural Mesothelioma (MPM).

Secondary Outcome Measures

Evaluate the safety of VS-6063 (defactinib) [Start of treatment through 30 days after the end of treatment, expected average of 6-8 weeks]
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.
Evaluate the pharmacokinetics of VS-6063 (defactinib) [Day 11 and Day 12, Day 21 and 28, or Day 35 and 42 (+/-2) days post-treatment]
PK (pharmacokinetic) parameters will include but not limited to peak and trough concentrations and AUC (area under curve), clearance, and elimination half-life will be characterized by average and variation summaries in the population.
To evaluate the tumor response to VS-6063 (defactinib) [Baseline and 12, 21 or 35 (+/-2) days post-treatment]
Tumor response will be assessed by Recist 1.1 modified for mesothelioma. The response rate will be reported with 95% exact confidence intervals based on the exact binomial distribution.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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