Ph 1 Study of VS-4718, a FAK Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Advanced Cancer Subjects
- Conditions
- Pancreatic Cancer
- Interventions
- Drug: Part A- VS-4718, nab-paclitaxel, gemcitabineDrug: Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabineDrug: Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine
- Registration Number
- NCT02651727
- Lead Sponsor
- Verastem, Inc.
- Brief Summary
The purpose of this study is to evaluate increasing dose levels of VS-4718 administered in combination with gemcitabine and nab-paclitaxel in subjects with advanced cancer and to determine a recommended Phase 2 dose (RP2D) for further development of this combination in subjects with untreated advanced pancreatic cancer.
- Detailed Description
The study is comprised of 2 sequential parts: Part A (Dose Escalation of VS-4718) in subjects with advanced cancer and Part B (Expansion) in subjects with untreated advanced pancreatic cancer.
Up to 60 evaluable subjects (i.e., subjects who complete at least 1 cycle (28 days) of therapy) will be enrolled, assuming that:
1. Part A: The maximum sample size will be 6 subjects up to 4 dose levels (exclusive of replacement subjects). However, additional subjects may be added if exploration of intermediate dose level(s) of VS 4718 is warranted. The starting dose of VS-4718 will be 200mg BID.
2. Part B: Up to 36 additional subjects may be enrolled at the RP2D. These subjects will be randomized at a 1:1 ratio to 1 of 2 treatment cohorts:
* Cohort 1: IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1
* Cohort 2: IV treatment for the first 2 cycles, followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 13
- Age ≥ 18 years
- Histologically or cytologically confirmed diagnosis of an advanced nonhematological malignancy (Part A) or advanced pancreatic adenocarcinoma (Part B) that is not surgically resectable
- Eligible for treatment with nab-paclitaxel and gemcitabine on Days 1, 8, and 15 in 28-day cycles as standard therapy
- Evaluable or measurable disease, as assessed by RECIST v1.1
- ECOG performance status of ≤ 1
- Adequate renal function (creatinine ≤ 1.5×ULN [upper limit of normal]) or glomerular filtration rate of ≥ 60 mL/min
- Adequate hepatic function (total bilirubin ≤ 1.5×ULN for the institution; aspartate transaminase and alanine transaminase ≤ 2.5×ULN, or ≤ 5×ULN if due to liver involvement by tumor; albumin ≥ 3 g/dL)
- Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; unsupported platelets ≥ 100×109 cells/L; absolute neutrophil count [ANC] ≥ 1.5×109 cells/L without the use of hematopoietic growth factors)
- Corrected QT interval (QTc) < 470 ms
- Willing and able to participate in the trial and comply with all trial requirements
- Gastrointestinal (GI) condition that 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 6 months prior to the first dose of protocol therapy
- Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of protocol therapy.
- Part B only: Prior therapy (including investigational agents) for pancreatic cancer
- Chemotherapy or radiotherapy within 14 days prior to first dose of protocol therapy
- Active treatment for a secondary malignancy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A- VS-4718, nab-paclitaxel, gemcitabine Part A- VS-4718, nab-paclitaxel, gemcitabine Part A- intravenous (IV) treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 twice-daily (BID) continuously starting on Cycle 1 Day 2. The starting dose of VS-4718 will be 200 mg BID. Part B, Cohort 2- VS-4718, nab-paclitaxel, gemcitabine Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabine Part B, Cohort 2- IV treatment for the first 2 cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15), followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3 Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine Part B, Cohort 1- IV treatment in 28-day cycles (nab-paclitaxel 125 mg/m2 over 30 minutes on Days 1, 8, and 15 and gemcitabine at 1000 mg/m2 over 30 minutes on Days 1, 8, and 15) and oral VS 4718 BID continuously starting on Day 1 of Cycle 1
- Primary Outcome Measures
Name Time Method Incidence of dose-limiting toxicities (DLTs) 6 months Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of VS-4718 in combination with gemcitabine and nab-paclitaxel
- Secondary Outcome Measures
Name Time Method Progression Free Survival From the date of first treatment to the date of progression including death from any cause, expected average at least 5 months Response rate (RR) Every 8 weeks from baseline through the end of treatment, an expected average of 5 months] RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Clearance Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Plasma concentration Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Area under the plasma concentration versus time curve (AUC) Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Maximum observed plasma concentration (Cmax) Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Time to reach maximum observed concentration (Tmax) Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Half life (T1/2) Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
Trial Locations
- Locations (2)
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Gettysburg Cancer Center
🇺🇸Gettysburg, Pennsylvania, United States