Ph 1 Study Of VS-4718, A FAK Inhibitor, In Combination With Nab-paclitaxel And Gemcitabine In Advanced Cancer Subjects

Study Overview

Ph 1 Study of VS-4718, a FAK Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Advanced Cancer Subjects

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

Pancreatic Cancer

DRUG: Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine
DRUG: Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabine
DRUG: Part A- VS-4718, nab-paclitaxel, gemcitabine

VS-4718-103

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-01-06	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2017-07-25
First Submitted that Met QC Criteria 2016-01-07	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2017-07-27
First Posted (ACTUAL) 2016-01-11	Results First Posted N/A	Last Verified 2017-01

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: 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	DRUG: Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine 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
EXPERIMENTAL: Part B, Cohort 2- VS-4718, 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 o	DRUG: Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabine IV treatment for the first 2 cycles, followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3
EXPERIMENTAL: 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	DRUG: 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

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: 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

DRUG: Part B, Cohort 1- VS-4718, nab-paclitaxel, gemcitabine

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

EXPERIMENTAL: Part B, Cohort 2- VS-4718, 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 o

DRUG: Part B, Cohort 2- VS4718, nab-paclitaxel, gemcitabine

IV treatment for the first 2 cycles, followed by IV treatment and oral VS-4718 BID continuously starting on Day 1 of Cycle 3

EXPERIMENTAL: 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

DRUG: 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

Primary Outcome Measures	Measure Description	Time Frame
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	6 months

Secondary Outcome Measures	Measure Description	Time Frame
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)	RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.	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 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

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_CHAIR: Hagop Youssoufian, MD, Verastem, Inc.

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

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Clinical Trial Record