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

NCT02004028 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: VS-6063-203
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Malignant Pleural Mesothelioma

Keywords

Mesothelioma; adenoma; Neoplasms, Mesothelial; Focal Adhesion Kinase Inhibitor

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• 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.

• 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.

Study Arms (1)

VS-6063 (defactinib)

EXPERIMENTAL

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

Drug: VS-6063

Interventions

VS-6063 DRUG

Also known as: defactinib

VS-6063 (defactinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Verastem, Inc.: lead

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Mesothelioma, Malignant; Mesothelioma; Adenoma; Neoplasms, Mesothelial

Interventions

defactinib

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Pleural Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Clinical Trials
• Organization: Verastem Oncology

clinicaltrials@verastem.com

+1-781-292-4204

Study Officials

• Raphael Bueno, M.D.

  Brigham and Women's Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2013
• First Posted: December 6, 2013
• Study Start: December 12, 2013
• Primary Completion: June 19, 2019
• Study Completion: June 19, 2019
• Last Updated: February 20, 2024
• Results First Posted: February 20, 2024

Record last verified: 2024-02

Locations

US (1)