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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Verastem, Inc.
Sponsor:
Information provided by (Responsible Party):
Verastem, Inc.
ClinicalTrials.gov Identifier:
NCT02004028
First received: December 2, 2013
Last updated: January 19, 2016
Last verified: January 2016
  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.

Condition Intervention Phase
Malignant Pleural Mesothelioma
Drug: VS-6063
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open Label Window of Opportunity Phase II Study of the FAK Inhibitor VS-6063 in Participants With Surgical Resectable Malignant Pleural Mesothelioma.

Resource links provided by NLM:


Further study details as provided by Verastem, Inc.:

Primary Outcome Measures:
  • Assess biomarker responses to VS-6063 in tumor tissue [ Time Frame: From Baseline to 12, 21 or 35 days (+/- 2 days) post-treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: Start of treatment through 30 days after the end of treatment, expected average of 6-8 weeks ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Day 11 and Day 12, Day 21 and 28, or Day 35 and 42 (+/-2) days post-treatment ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline and 12, 21 or 35 (+/-2) days post-treatment ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 35
Study Start Date: December 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: VS-6063 (defactinib)
Administered orally (BID) for 12, 21 or 35 days (+/- 2 days)
Drug: VS-6063
Other Name: defactinib

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02004028

Contacts
Contact: Laurie J LoBue, RN, BSN 781-292-4247 llobue@verastem.com

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Julianne Barlow    617-525-8541    jbarlow1@partners.org   
Contact: Raphael Bueno, M.D.    617-732-8148    rbueno@partners.org   
Principal Investigator: Raphael Bueno, M.D.         
Sub-Investigator: David Jackman, M.D.         
Sponsors and Collaborators
Verastem, Inc.
Investigators
Study Chair: Raphael Bueno, M.D. Brigham and Women's Hospital
  More Information

Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT02004028     History of Changes
Other Study ID Numbers: VS-6063-203 
Study First Received: December 2, 2013
Last Updated: January 19, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Verastem, Inc.:
Mesothelioma
adenoma
Neoplasms, Mesothelial
Focal Adhesion Kinase Inhibitor

Additional relevant MeSH terms:
Mesothelioma
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial

ClinicalTrials.gov processed this record on July 25, 2016