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

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ClinicalTrials.gov Identifier: NCT01849744
Recruitment Status : Terminated (Sponsor's decision to deprioritize the program.)
First Posted : May 8, 2013
Last Update Posted : July 28, 2017
Sponsor:
Information provided by (Responsible Party):
Verastem, Inc.

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.

Condition or disease Intervention/treatment Phase
Non Hematologic Cancers Metastatic Cancer Drug: VS-4718 Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Subjects With Metastatic Non-Hematologic Malignancies
Study Start Date : June 2013
Actual Primary Completion Date : April 2017
Actual Study Completion Date : June 2017

Arm Intervention/treatment
Experimental: VS-4718
Oral VS-4718 administered BID (QD during first cohort) during a 28 day cycle.
Drug: VS-4718



Primary Outcome Measures :
  1. Assess the safety and tolerability of VS-4718 in subjects with metastatic non-hematologic malignancies [ Time Frame: Expected average of 12 weeks from start of treatment to end of treatment ]
    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.

  2. Establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of VS-4718 in subjects with metastatic non-hematologic malignancies [ Time Frame: From start of treatment to end of cycle 1 (4 week cycles) ]
    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.


Secondary Outcome Measures :
  1. Evaluate the efficacy of VS-4718 [ Time Frame: Every 8 weeks to end of treatment, expected average of 16 weeks ]
    Response rate and progression-free survival as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1

  2. Evaluate duration of response to VS-4718 compared with duration of response to prior therapy. [ Time Frame: Expected average of 16 weeks from start of treatment to end of treatment ]
  3. Assess the pharmacokinetics of VS-4718 [ Time Frame: Time points on Day 1, 2, 8, 15, 16, and 29 ]
    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

  4. Evaluate biomarkers of VS-4718 activity [ Time Frame: Day 1 and Day 15 of treatment ]
    Pre and post dose biomarker analysis in serum and tumor samples to identify possible prognostic factors to VS-4718 response

  5. Examine if the tumor expression status of pFAK and other plasma biomarkers correlates with response to VS-4718 therapy [ Time Frame: From start of treatment to end of treatment, an expected average of 16 weeks ]
    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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01849744


Locations
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United States, Arizona
HonorHealth Research Institute
Scottsdale, Arizona, United States, 85258
United States, California
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States, 34232
United States, Missouri
Washington University School of Medicine, Division of Oncology
Saint Louis, Missouri, United States, 63110
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Verastem, Inc.
Investigators
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Study Chair: Hagop Youssoufian, MD Verastem, Inc.

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Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT01849744     History of Changes
Other Study ID Numbers: VS-4718-101
First Posted: May 8, 2013    Key Record Dates
Last Update Posted: July 28, 2017
Last Verified: July 2017

Keywords provided by Verastem, Inc.:
Focal Adhesion Kinase inhibitor
FAK inhibitor
Cancer Stem Cells
CSC

Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes