Metastatic Cancer, Non Hematologic Cancers
Conditions
Keywords
Focal Adhesion Kinase inhibitor, FAK inhibitor, Cancer Stem Cells, CSC
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.
Interventions
DRUGVS-4718
Sponsors
Verastem, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assess the safety and tolerability of VS-4718 in subjects with metastatic non-hematologic malignancies | 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. |
| Establish the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of VS-4718 in subjects with metastatic non-hematologic malignancies | 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
| Measure | Time frame | Description |
|---|---|---|
| Assess the pharmacokinetics of VS-4718 | 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 |
| Evaluate the efficacy of VS-4718 | 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 |
| 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 | 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 |
| Evaluate biomarkers of VS-4718 activity | 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 |
| 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 | — |
Countries
United States
Outcome results
None listed