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

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

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 Overview

• Status: Terminated
• Conditions: Malignant Pleural Mesothelioma
• Intervention / Treatment: Drug: VS-6063

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Cohort 1, 40 days; Cohort 2, 42 days; Cohort 3, 28 days; Cohort 4, 28 days.

Collaborators and Investigators

• Sponsor: Verastem, Inc.
• Investigators: Study Chair: Raphael Bueno, M.D., Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2013
• Primary Completion (Actual): June 19, 2019
• Study Completion (Actual): June 19, 2019

Study Registration Dates

• First Submitted: December 2, 2013
• First Submitted That Met QC Criteria: December 2, 2013
• First Posted (Estimated): December 6, 2013

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 16, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: adenoma; Mesothelioma; Neoplasms, Mesothelial; Focal Adhesion Kinase Inhibitor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma; Mesothelioma, Malignant
• Other Study ID Numbers: VS-6063-203

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No