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

Primary Purpose

Malignant Pleural Mesothelioma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
VS-6063
Sponsored by
Verastem, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Pleural Mesothelioma focused on measuring Mesothelioma, adenoma, Neoplasms, Mesothelial, Focal Adhesion Kinase Inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Brigham and Women's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

VS-6063 (defactinib)

Arm Description

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

Outcomes

Primary Outcome Measures

Assess biomarker responses to VS-6063 in tumor tissue
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)
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)
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)
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.

Full Information

First Posted
December 2, 2013
Last Updated
May 13, 2021
Sponsor
Verastem, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02004028
Brief Title
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

2. Study Status

Record Verification Date
May 2021
Overall Recruitment Status
Terminated
Why Stopped
Company decided to discontinue trial to focus on development program next steps
Study Start Date
December 12, 2013 (Actual)
Primary Completion Date
June 19, 2019 (Actual)
Study Completion Date
June 19, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Verastem, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Pleural Mesothelioma
Keywords
Mesothelioma, adenoma, Neoplasms, Mesothelial, Focal Adhesion Kinase Inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Actual)

8. Arms, Groups, and Interventions

Arm Title
VS-6063 (defactinib)
Arm Type
Experimental
Arm Description
Administered orally (BID) for 12, 21 or 35 days (+/- 2 days)
Intervention Type
Drug
Intervention Name(s)
VS-6063
Other Intervention Name(s)
defactinib
Primary Outcome Measure Information:
Title
Assess biomarker responses to VS-6063 in tumor tissue
Description
To determine biomarker responses to the Focal Adhesion Kinase (FAK) inhibitor, VS-6063 (defactinib), in Malignant Pleural Mesothelioma (MPM).
Time Frame
From Baseline to 12, 21 or 35 days (+/- 2 days) post-treatment
Secondary Outcome Measure Information:
Title
Evaluate the safety of VS-6063 (defactinib)
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.
Time Frame
Start of treatment through 30 days after the end of treatment, expected average of 6-8 weeks
Title
Evaluate the pharmacokinetics of VS-6063 (defactinib)
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.
Time Frame
Day 11 and Day 12, Day 21 and 28, or Day 35 and 42 (+/-2) days post-treatment
Title
To evaluate the tumor response to VS-6063 (defactinib)
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.
Time Frame
Baseline and 12, 21 or 35 (+/-2) days post-treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raphael Bueno, M.D.
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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