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

NCT01849744 | Terminated Phase 1

• 1 other identifier: VS-4718-101
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Non Hematologic Cancers; Metastatic Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• Evaluate the efficacy of VS-4718

  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

  Time points on Day 1, 2, 8, 15, 16, and 29

• Evaluate biomarkers of VS-4718 activity

  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

  From start of treatment to end of treatment, an expected average of 16 weeks

Study Arms (1)

VS-4718

EXPERIMENTAL

Oral VS-4718 administered BID (QD during first cohort) during a 28 day cycle.

Drug: VS-4718

Interventions

VS-4718 DRUG

VS-4718

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Verastem, Inc.: lead

Study Sites (5)

HonorHealth Research Institute

Scottsdale, Arizona, 85258, United States

Location

Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Washington University School of Medicine, Division of Oncology

St Louis, Missouri, 63110, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

PND 1186

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Hagop Youssoufian, MD

  Verastem, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2013
• First Posted: May 8, 2013
• Study Start: June 1, 2013
• Primary Completion: April 1, 2017
• Study Completion: June 1, 2017
• Last Updated: July 28, 2017

Record last verified: 2017-07

Locations

US (5)