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Phase II Study of VS-6063 in Patients With KRAS Mutant Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01951690
Recruitment Status : Completed
First Posted : September 27, 2013
Last Update Posted : April 13, 2017
Sponsor:
Information provided by (Responsible Party):
Verastem, Inc.

Study Description
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Brief Summary:
This is a Phase II, open-label, multicenter, multi cohort, study of VS-6063 (defactinib), a focal adhesion kinase inhibitor, in patients with KRAS mutant non-small cell lung cancer (NSCLC). NSCLC with a KRAS mutation is required for study entry and subjects will be enrolled into 1 of 4 cohorts based on the status of their INK4a/Arf and p53 mutations. The purpose of this study is to demonstrate if VS-6063 (defactinib) improves PFS within each cohort. The safety and tolerability of VS-6063, tumor response rate, progression free survival and overall survival will also be assessed. The pharmacodynamic effects of VS-6063 (defactinib) will be examined in a tumor biopsy and a blood sample.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Lung Cancer Drug: defactinib (VS-6063) Phase 2

Detailed Description:
Eleven subjects will be enrolled into one of four cohorts: Cohort A (KRAS mutation, wild type INK4a/ARF and wildtype p53), Cohort B (KRAS mutation, INK4s/ARF mutation and wild type p53), Cohort C (KRAS mutation, wild type INK4a/ARF and p53 mutation), and Cohort D (KRAS mutation, INK4a/ARF mutation and p53 mutation). If >/= 4 patients demonstrate PFS at 12 weeks in each cohort, an additional 23 subjects will be enrolled.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of VS-6063, A Focal Adhesion Kinase (FAK) Inhibitor, in Patients With KRAS Mutant Non-Small Cell Lung Cancer
Study Start Date : September 2013
Actual Primary Completion Date : June 2016
Actual Study Completion Date : June 2016

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: VS-6063 (defactinib)
Administered orally BID in a 21 day cycle
 Drug: defactinib (VS-6063)


Outcome Measures
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Primary Outcome Measures :
  1. Demonstrate that VS-6063 (defactinib), will improve PFS at 12 weeks (PFS12) within each cohort. [ Time Frame: From baseline through 12 weeks of treatment ]

Secondary Outcome Measures :
  1. Evaluate the response rate (RR) [ Time Frame: Every 6 weeks from baseline through the end of treatment, an expected average of 4 months ]
    RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.

  2. Evaluate progression free survival [ Time Frame: From the date of first treatment to the date of progression including death from any cause, expected average at least 4 months ]
    PFS will be estimated in each cohort using Kaplan-Meier product limit estimates.

  3. Evaluate Overall Survival (OS) [ Time Frame: OS will be calculated from the date of first treatment to the date of death from any cause, expected average of at least 12 months. Patients who did not experience death will be censored at the last follow-up time. ]
    OS in each cohort will be estimated using Kaplan-Meier product limit estimates.


Other Outcome Measures:
  1. Evaluation of the association between pharmacodynamic (PD) biomarkers and clinical outcomes (response rate, progression-free survival and overall survival) [ Time Frame: Baseline PD biomarkers will be associated with the RR (collected every 6 weeks) and PFS, both with expected average of 4 months from first treatment to progression, and OS (expected average of 12 months from first treatment to date of death) ]
  2. Evaluate the safety and tolerability of VS-6063 (defactinib) [ Time Frame: From start of treatment to end of treatment, an expected average of 4 months ]
    Adverse events (AEs) include the incidences of all treatment-emergent AEs (TEAEs) and all Serious Adverse Events (SAEs); by severity, relationship to study drug, and discontinuation of patients from study therapy due to AEs and due to deaths. Safety endpoints for AEs, clinical laboratory tests, vital signs, ECGs and physical examinations will be summarized using descriptive statistics as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03


Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • ≥ 18 years of age.
  • ECOG (Eastern Cooperative Oncology Group) Performance Score of 0 or 1.
  • Histologic or cytologic confirmation of non-small cell lung cancer (NSCLC)
  • Molecular characterization of the tumor demonstrating a KRAS mutation by a CLIA-certified assay. Adequate archival tissue, tissue core biopsy specimen, or DNA samples must be available for central testing of INK4a/Arf and p53 if not previously performed by a CLIA certified lab.
  • Documented evidence of distant metastasis or locoregional recurrence per required assessments within 28 days prior to starting study therapy.

Note: Histologic confirmation of metastatic disease is not required.

  • For patients with brain metastases, the following criteria must be met:

Previously untreated brain metastases that are asymptomatic and not requiring steroids are permitted.

Previously treated brain metastases are permitted if most recent CNS radiographic imaging demonstrates no evidence of CNS disease progression For patients with previously untreated brain metastases, Central Nervous System (CNS) imaging is required at the time of disease imaging throughout treatment.

  • At least one measurable disease site per RECIST v1.1.
  • Received a minimum of one course of treatment that included at least one platinum-based chemotherapy doublet for metastatic or locally recurrent disease.
  • Adequate hematologic function including ANC ≥ 1200/mm3, Hemoglobin ≥ 9 g/dL (transfusion is permitted), and platelets ≥ 100,000/mm3.
  • Adequate hepatic function including ALT ≤ 2.5 x upper limit of normal (ULN) if liver metastasis is NOT present or ≤ 5 x ULN if liver metastasis is present, and total bilirubin ≤ 1.5 x ULN.
  • QTc (corrected QT) interval < 480 msec.

Exclusion Criteria:

  • Presence of an activating EGFR (epidermal growth factor receptor) mutation or ALK (anaplastic lymphoma kinase) translocation in the tumor.
  • Radiotherapy (RT) completed within 14 days prior to the first dose of study therapy.
  • Known impairment of gastrointestinal function that would alter drug absorption.
  • Leptomeningeal metastasis.
  • Symptomatic or untreated brain metastases or spinal cord compression or any of these conditions requiring chronic steroids to control symptoms.
  • History or evidence of cardiac risk
  • Known history of malignant hypertension (severe hypertension >180/120 mmHg with end organ involvement.
  • Another active concurrent malignancy.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01951690


Locations
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United States, Colorado
University of Colorado Cancer Center, Anschutz Medical Campus
Denver, Colorado, United States, 80045
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21287
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, Oregon
Knight Cancer Institute, Oregon Health and Science University
Portland, Oregon, United States, 97239
United States, Pennsylvania
University of Pittsburgh Medical Center Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
University of Texas Southwestern Medical Center
Dallas, Texas, United States, 75390-8852
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229-3900
Sponsors and Collaborators
Verastem, Inc.
Investigators
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Principal Investigator: David E Gerber, M.D. University of Texas Southwestern Medical Center
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT01951690    
Other Study ID Numbers: VS-6063-201
First Posted: September 27, 2013    Key Record Dates
Last Update Posted: April 13, 2017
Last Verified: April 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Verastem, Inc.:
Focal Adhesion Kinase inhibitor
FAK inhibitor
Cancer Stem Cells
CSC
KRAS mutation
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
 Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms