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

April 12, 2017 updated by: Verastem, Inc.

Phase II Study of VS-6063, A Focal Adhesion Kinase (FAK) Inhibitor, in Patients With KRAS Mutant Non-Small Cell Lung Cancer

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Colorado
      • Denver, Colorado, United States, 80045
        • University of Colorado Cancer Center, Anschutz Medical Campus
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Winship Cancer Institute of Emory University
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School Of Medicine
    • Oregon
      • Portland, Oregon, United States, 97239
        • Knight Cancer Institute, Oregon Health and Science University
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute
    • Texas
      • Dallas, Texas, United States, 75390-8852
        • University of Texas Southwestern Medical Center
      • San Antonio, Texas, United States, 78229-3900
        • The University of Texas Health Science Center at San Antonio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VS-6063 (defactinib)
Administered orally BID in a 21 day cycle
Drug: defactinib (VS-6063)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Every 6 weeks from baseline through the end of treatment, an expected average of 4 months
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.
From the date of first treatment to the date of progression including death from any cause, expected average at least 4 months
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.
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.

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
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)
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)
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
From start of treatment to end of treatment, an expected average of 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Verastem, Inc.

Investigators

  • Principal Investigator: David E Gerber, M.D., University of Texas Southwestern Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

June 1, 2016

Study Completion (Actual)

June 1, 2016

Study Registration Dates

First Submitted

September 23, 2013

First Submitted That Met QC Criteria

September 26, 2013

First Posted (Estimate)

September 27, 2013

Study Record Updates

Last Update Posted (Actual)

April 13, 2017

Last Update Submitted That Met QC Criteria

April 12, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VS-6063-201

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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