Clinical trial NCT01849744: 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
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non Hematologic Cancers
Metastatic Cancer
Keywords: Focal Adhesion Kinase inhibitor
FAK inhibitor
Cancer Stem Cells
CSC
Lead sponsor: Verastem, Inc.
Sponsor class: INDUSTRY
First posted: 2013-05-08
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Assess the safety and tolerability of VS-4718 in subjects with metastatic non-hematologic malignancies
timeFrame: Expected average of 12 weeks from start of treatment to end of treatment
measure: Establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of VS-4718 in subjects with metastatic non-hematologic malignancies
timeFrame: From start of treatment to end of cycle 1 (4 week cycles)
Secondary outcomes:
measure: Evaluate the efficacy of VS-4718
timeFrame: Every 8 weeks to end of treatment, expected average of 16 weeks
measure: Evaluate duration of response to VS-4718 compared with duration of response to prior therapy.
timeFrame: Expected average of 16 weeks from start of treatment to end of treatment
measure: Assess the pharmacokinetics of VS-4718
timeFrame: Time points on Day 1, 2, 8, 15, 16, and 29
measure: Evaluate biomarkers of VS-4718 activity
timeFrame: Day 1 and Day 15 of treatment
measure: Examine if the tumor expression status of pFAK and other plasma biomarkers correlates with response to VS-4718 therapy
timeFrame: From start of treatment to end of treatment, an expected average of 16 weeks
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Los Angeles
country: United States
facility: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Division of Oncology
state: Missouri
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
Study officials:
affiliation: Verastem, Inc.
name: Hagop Youssoufian, MD
role: STUDY_CHAIR
References: