Back to resultsPhase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies
Primary Purpose
Non Hematologic Cancers, Metastatic Cancer
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
VS-4718
Sponsored by
About this trial
This is an interventional treatment trial for Non Hematologic Cancers focused on measuring Focal Adhesion Kinase inhibitor, FAK inhibitor, Cancer Stem Cells, CSC
Eligibility 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.
Sites / Locations
- HonorHealth Research Institute
- Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
- Florida Cancer Specialists
- Washington University School of Medicine, Division of Oncology
- Sarah Cannon Research Institute
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
VS-4718
Arm Description
Oral VS-4718 administered BID (QD during first cohort) during a 28 day cycle.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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
Evaluate duration of response to VS-4718 compared with duration of response to prior therapy.
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01849744
Brief Title
Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies
Official Title
A Phase I Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Subjects With Metastatic Non-Hematologic Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
July 2017
Overall Recruitment Status
Terminated
Why Stopped
Sponsor's decision to deprioritize the program.
Study Start Date
June 2013 (undefined)
Primary Completion Date
April 2017 (Actual)
Study Completion Date
June 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Verastem, Inc.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Hematologic Cancers, Metastatic Cancer
Keywords
Focal Adhesion Kinase inhibitor, FAK inhibitor, Cancer Stem Cells, CSC
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
48 (Actual)
8. Arms, Groups, and Interventions
Arm Title
VS-4718
Arm Type
Experimental
Arm Description
Oral VS-4718 administered BID (QD during first cohort) during a 28 day cycle.
Intervention Type
Drug
Intervention Name(s)
VS-4718
Primary Outcome Measure Information:
Title
Assess the safety and tolerability of VS-4718 in subjects with metastatic non-hematologic malignancies
Description
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.
Time Frame
Expected average of 12 weeks from start of treatment to end of treatment
Title
Establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of VS-4718 in subjects with metastatic non-hematologic malignancies
Description
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.
Time Frame
From start of treatment to end of cycle 1 (4 week cycles)
Secondary Outcome Measure Information:
Title
Evaluate the efficacy of VS-4718
Description
Response rate and progression-free survival as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1
Time Frame
Every 8 weeks to end of treatment, expected average of 16 weeks
Title
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
Title
Assess the pharmacokinetics of VS-4718
Description
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 Frame
Time points on Day 1, 2, 8, 15, 16, and 29
Title
Evaluate biomarkers of VS-4718 activity
Description
Pre and post dose biomarker analysis in serum and tumor samples to identify possible prognostic factors to VS-4718 response
Time Frame
Day 1 and Day 15 of treatment
Title
Examine if the tumor expression status of pFAK and other plasma biomarkers correlates with response to VS-4718 therapy
Description
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
Time Frame
From start of treatment to end of treatment, an expected average of 16 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hagop Youssoufian, MD
Organizational Affiliation
Verastem, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
HonorHealth Research Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Facility Name
Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Florida Cancer Specialists
City
Sarasota
State/Province
Florida
ZIP/Postal Code
34232
Country
United States
Facility Name
Washington University School of Medicine, Division of Oncology
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies
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