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.
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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
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
IV treatment for the first 2 cycles, followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3
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.
Washington University School of Medicine
St Louis, Missouri, United States
Gettysburg Cancer Center
Gettysburg, Pennsylvania, United States
Incidence of dose-limiting toxicities (DLTs)
Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of VS-4718 in combination with gemcitabine and nab-paclitaxel
Time frame: 6 months
Progression Free Survival
Time frame: 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)
RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.
Time frame: Every 8 weeks from baseline through the end of treatment, an expected average of 5 months]
Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Clearance
Time frame: 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 frame: 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 frame: 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 frame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle
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Pharmacokinetics of VS-4718 in combination with nab-paclitaxel and gemcitabine: Time to reach maximum observed concentration (Tmax)
Time frame: 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 frame: Time points on Day 1, 2,15, 16, and 22 in Cycle 1; Day 1 of each subsequent cycle