Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies

A Phase I Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Subjects With Metastatic Non-Hematologic Malignancies

This is a Phase I, open-label, multicenter, dose-escalation trial of VS-4718, a focal adhesion kinase inhibitor, in subjects with metastatic non-hematologic malignancies. This clinical study is comprised of 2 parts: Part 1 (Dose Escalation) and Part 2 (Expansion). The purpose of this study is to evaluate the safety (including the recommended Phase II dose), pharmacokinetics (the amount of VS-4718 in your blood) and the anti-cancer activity of VS-4718. The pharmacodynamic effects (genes or proteins that may predict or show how your body may respond to VS-4718) will also be examined in tumor biopsies and blood samples.

Study Overview

• Status: Terminated
• Conditions: Metastatic Cancer; Non Hematologic Cancers
• Intervention / Treatment: Drug: VS-4718

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • California
    • Los Angeles, California, United States, 90048
      • Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
  • Florida
    • Sarasota, Florida, United States, 34232
      • Florida Cancer Specialists
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine, Division of Oncology
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18 years.
• Histopathologically confirmed diagnosis of a metastatic non-hematologic malignancy.
• ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 2
• Adequate renal function
• Adequate hepatic function (total bilirubin ≤ 1.5x ULN (upper limit of normal) for the institution; AST [aspartate transaminase] and ALT [alanine transaminase] ≤ 3x ULN, or ≤ 5x ULN if due to liver involvement by tumor).
• Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; unsupported platelets ≥ 100 x10 9 cells/L; absolute neutrophil count ≥ 1.5x10 9 cells/L
• Corrected QT interval (QTc) < 470 ms
• Subjects must have at least one tumor lesion that is suitable for repeat biopsy, and must agree to two tumor biopsies (pre- and post- treatment).
• Willing and able to participate in the trial and comply with all trial requirements.

Exclusion Criteria:

• Gastrointestinal (GI) condition which could interfere with the swallowing or absorption of study medication.
• Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases).
• History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months.
• Known history of stroke or cerebrovascular accident within 6 months.
• Subjects being actively treated for a secondary malignancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: VS-4718; Oral VS-4718 administered BID (QD during first cohort) during a 28 day cycle.	Drug: VS-4718

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess the safety and tolerability of VS-4718 in subjects with metastatic non-hematologic malignancies	Serious Adverse events, Adverse events and their frequency, duration and severity, physical examination, laboratory parameters, vital signs and ECGs as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) V4.03. A Safety monitoring committee will review safety information.	Expected average of 12 weeks from start of treatment to end of treatment
Establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of VS-4718 in subjects with metastatic non-hematologic malignancies	The RP2D will be determined based on the maximum tolerated dose (MTD) of VS-4718 as determined by number of participants with dose limiting toxicities related to VS-4718. Observations related to pharmacokinetics, pharmacodynamics, and any VS-4718 related toxicities may be included in the rationale supporting the RP2D and will not exceed the MTD.	From start of treatment to end of cycle 1 (4 week cycles)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the efficacy of VS-4718	Response rate and progression-free survival as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1	Every 8 weeks to end of treatment, expected average of 16 weeks
Evaluate duration of response to VS-4718 compared with duration of response to prior therapy.		Expected average of 16 weeks from start of treatment to end of treatment
Assess the pharmacokinetics of VS-4718	PK (pharmacokinetics) parameters, including but not limited to clearance, plasma concentration, AUC (Area Under Curve, 0-24 and 0-t), Cmax, Tmax, and T1/2	Time points on Day 1, 2, 8, 15, 16, and 29
Evaluate biomarkers of VS-4718 activity	Pre and post dose biomarker analysis in serum and tumor samples to identify possible prognostic factors to VS-4718 response	Day 1 and Day 15 of treatment
Examine if the tumor expression status of pFAK and other plasma biomarkers correlates with response to VS-4718 therapy	Tumor expression status (pFAK, cancer stem cells, CSC, and other biomarkers) compared with response to VS-4718, as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1	From start of treatment to end of treatment, an expected average of 16 weeks

Collaborators and Investigators

• Sponsor: Verastem, Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (ACTUAL): April 1, 2017
• Study Completion (ACTUAL): June 1, 2017

Study Registration Dates

• First Submitted: May 6, 2013
• First Submitted That Met QC Criteria: May 6, 2013
• First Posted (ESTIMATE): May 8, 2013

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2017
• Last Update Submitted That Met QC Criteria: July 25, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: CSC; Cancer Stem Cells; Focal Adhesion Kinase inhibitor; FAK inhibitor
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis
• Other Study ID Numbers: VS-4718-101