Clinical trial NCT02004028: Window of Opportunity Study of VS-6063 (Defactinib) in Surgical Resectable Malignant Pleural Mesothelioma Participants
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Malignant Pleural Mesothelioma
Keywords: Mesothelioma
adenoma
Neoplasms, Mesothelial
Focal Adhesion Kinase Inhibitor
Lead sponsor: Verastem, Inc.
Sponsor class: INDUSTRY
First posted: 2013-12-06
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of pFAK Inhibition in Tumor Tissue
timeFrame: 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.
measure: Evaluate the Pharmacokinetics of VS-6063 (Defactinib), CMax
timeFrame: 0-24 hours
measure: Evaluate the Pharmacokinetics of VS-6063 (Defactinib), AUC (Area Under the Curve)
timeFrame: 0-8 hours
measure: Evaluate the Pharmacokinetics of VS-6063 (Defactinib), Median Tmax (h)
timeFrame: 0-24 hours
Secondary outcomes:
measure: Number of Patients With at Least One Adverse Event
timeFrame: Cohort 1, 40 days; Cohort 2, 42 days; Cohort 3, 28 days; Cohort 4, 28 days.
measure: To Evaluate the Tumor Response to VS-6063 (Defactinib)
timeFrame: Cohort 1, 40 days; Cohort 2, 42 days; Cohort 3, 28 days; Cohort 4, 28 days.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Raphael Bueno, M.D.
role: STUDY_CHAIR
References: