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

NCT01951690 | Completed Phase 2 FDA Drug

• 1 other identifier: VS-6063-201
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 9

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.

Conditions

Non Small Cell Lung Cancer; Lung Cancer

Keywords

Focal Adhesion Kinase inhibitor; FAK inhibitor; Cancer Stem Cells; CSC; KRAS mutation

Outcome Measures

Primary Outcomes (1)

• Demonstrate that VS-6063 (defactinib), will improve PFS at 12 weeks (PFS12) within each cohort.

  From baseline through 12 weeks of treatment

Secondary Outcomes (3)

• Evaluate the response rate (RR)

  Every 6 weeks from baseline through the end of treatment, an expected average of 4 months

• Evaluate progression free survival

  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)

  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 Outcomes (2)

• 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)

• Evaluate the safety and tolerability of VS-6063 (defactinib)

  From start of treatment to end of treatment, an expected average of 4 months

Study Arms (1)

VS-6063 (defactinib)

EXPERIMENTAL

Administered orally BID in a 21 day cycle

Drug: defactinib (VS-6063)

Interventions

defactinib (VS-6063) DRUG

VS-6063 (defactinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Verastem, Inc.: lead

Study Sites (9)

University of Colorado Cancer Center, Anschutz Medical Campus

Denver, Colorado, 80045, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Knight Cancer Institute, Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-8852, United States

Location

The University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229-3900, United States

Location

Related Publications (1)

• 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.

  PMID: 27025608 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

defactinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• David E Gerber, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2013
• First Posted: September 27, 2013
• Study Start: September 1, 2013
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: April 13, 2017

Record last verified: 2017-04

Locations

US (9)