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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01951690
• Other study ID #: VS-6063-201
• Status: Completed
• Phase: Phase 2
• First received: September 23, 2013
• Last updated: April 12, 2017
• Start date: September 2013
• Est. completion date: June 2016

Study information

• Verified date: April 2017
• Source: Verastem, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• defactinib (VS-6063)

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Colorado Cancer Center, Anschutz Medical Campus	Denver	Colorado
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	University of Pittsburgh Medical Center Cancer Center	Pittsburgh	Pennsylvania
United States	Knight Cancer Institute, Oregon Health and Science University	Portland	Oregon
United States	The University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Verastem, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluation of the association between pharmacodynamic (PD) biomarkers and clinical outcomes (response rate, progression-free survival and overall survival)		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)
Other	Evaluate the safety and tolerability of VS-6063 (defactinib)	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
Primary	Demonstrate that VS-6063 (defactinib), will improve PFS at 12 weeks (PFS12) within each cohort.		From baseline through 12 weeks of treatment
Secondary	Evaluate the response rate (RR)	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
Secondary	Evaluate progression free survival	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
Secondary	Evaluate Overall Survival (OS)	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.