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

Metastatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01849744
• Other study ID #: VS-4718-101
• Status: Terminated
• Phase: Phase 1
• First received: May 6, 2013
• Last updated: July 25, 2017
• Start date: June 2013
• Est. completion date: June 2017

Study information

• Verified date: July 2017
• Source: Verastem, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 48
• Est. completion date: June 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Non Hematologic Cancers

Intervention

Drug:
• VS-4718

Locations

Country	Name	City	State
United States	Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Washington University School of Medicine, Division of Oncology	Saint Louis	Missouri
United States	Florida Cancer Specialists	Sarasota	Florida
United States	HonorHealth Research Institute	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Verastem, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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