Clinical Trials /

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

NCT02004028

Description:

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.

Related Conditions:
  • Malignant Pleural Mesothelioma
Recruiting Status:

Terminated

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Window of Opportunity Study of VS-6063 (Defactinib) in Participants With Surgical Resectable Malignant Pleural Mesothelioma.
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: VS-6063-203
  • NCT ID: NCT02004028

Conditions

  • Malignant Pleural Mesothelioma

Interventions

DrugSynonymsArms
VS-6063defactinibVS-6063 (defactinib)

Purpose

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. 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.

Trial Arms

NameTypeDescriptionInterventions
VS-6063 (defactinib)ExperimentalAdministered orally (BID) for 12, 21 or 35 days (+/- 2 days)
  • VS-6063

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Evaluate the safety of VS-6063 (defactinib)
Time Frame:Start of treatment through 30 days after the end of treatment, expected average of 6-8 weeks
Safety Issue:
Description: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.
Measure:Evaluate the pharmacokinetics of VS-6063 (defactinib)
Time Frame:Day 11 and Day 12, Day 21 and 28, or Day 35 and 42 (+/-2) days post-treatment
Safety Issue:
Description: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.
Measure:To evaluate the tumor response to VS-6063 (defactinib)
Time Frame:Baseline and 12, 21 or 35 (+/-2) days post-treatment
Safety Issue:
Description: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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Verastem, Inc.

Trial Keywords

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

Last Updated

February 1, 2017