Back to resultsPhase II Study of VS-6063 in Patients With KRAS Mutant Non-Small Cell Lung Cancer
Primary Purpose
Non Small Cell Lung Cancer, Lung Cancer
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
defactinib (VS-6063)
Sponsored by
About this trial
This is an interventional treatment trial for Non Small Cell Lung Cancer focused on measuring Focal Adhesion Kinase inhibitor, FAK inhibitor, Cancer Stem Cells, CSC, KRAS mutation
Eligibility 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.
Sites / Locations
- University of Colorado Cancer Center, Anschutz Medical Campus
- Winship Cancer Institute of Emory University
- Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
- Washington University School of Medicine
- Knight Cancer Institute, Oregon Health and Science University
- University of Pittsburgh Medical Center Cancer Center
- Sarah Cannon Research Institute
- University of Texas Southwestern Medical Center
- The University of Texas Health Science Center at San Antonio
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
VS-6063 (defactinib)
Arm Description
Administered orally BID in a 21 day cycle
Outcomes
Primary Outcome Measures
Demonstrate that VS-6063 (defactinib), will improve PFS at 12 weeks (PFS12) within each cohort.
Secondary Outcome Measures
Evaluate the response rate (RR)
RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.
Evaluate progression free survival
PFS will be estimated in each cohort using Kaplan-Meier product limit estimates.
Evaluate Overall Survival (OS)
OS in each cohort will be estimated using Kaplan-Meier product limit estimates.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01951690
Brief Title
Phase II Study of VS-6063 in Patients With KRAS Mutant Non-Small Cell Lung Cancer
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 Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (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
No
5. Study Description
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Small Cell Lung Cancer, Lung Cancer
Keywords
Focal Adhesion Kinase inhibitor, FAK inhibitor, Cancer Stem Cells, CSC, KRAS mutation
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
55 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VS-6063 (defactinib)
Arm Type
Experimental
Arm Description
Administered orally BID in a 21 day cycle
Intervention Type
Drug
Intervention Name(s)
defactinib (VS-6063)
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
Evaluate the response rate (RR)
Description
RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.
Time Frame
Every 6 weeks from baseline through the end of treatment, an expected average of 4 months
Title
Evaluate progression free survival
Description
PFS will be estimated in each cohort using Kaplan-Meier product limit estimates.
Time Frame
From the date of first treatment to the date of progression including death from any cause, expected average at least 4 months
Title
Evaluate Overall Survival (OS)
Description
OS in each cohort will be estimated using Kaplan-Meier product limit estimates.
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.
Other Pre-specified Outcome Measures:
Title
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)
Title
Evaluate the safety and tolerability of VS-6063 (defactinib)
Description
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
Time Frame
From start of treatment to end of treatment, an expected average of 4 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David E Gerber, M.D.
Organizational Affiliation
University of Texas Southwestern Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Colorado Cancer Center, Anschutz Medical Campus
City
Denver
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Winship Cancer Institute of Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
Washington University School of Medicine
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Knight Cancer Institute, Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Pittsburgh Medical Center Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-8852
Country
United States
Facility Name
The University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229-3900
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27025608
Citation
Shimizu T, Fukuoka K, Takeda M, Iwasa T, Yoshida T, Horobin J, Keegan M, Vaickus L, Chavan A, Padval M, Nakagawa K. A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol. 2016 May;77(5):997-1003. doi: 10.1007/s00280-016-3010-1. Epub 2016 Mar 30.
Results Reference
derived
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Phase II Study of VS-6063 in Patients With KRAS Mutant Non-Small Cell Lung Cancer
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