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

Pancreatic Cancer Clinical Trial

Official title:

A Phase 1 Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Subjects With Advanced Cancer

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02651727
• Other study ID #: VS-4718-103
• Status: Terminated
• Phase: Phase 1
• First received: January 6, 2016
• Last updated: July 25, 2017
• Start date: September 2015
• Est. completion date: January 2017

Study information

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

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 13
• Est. completion date: January 2017
• Est. primary completion date: January 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

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
• 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
• 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.

Locations

Country	Name	City	State
United States	Gettysburg Cancer Center	Gettysburg	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Verastem, Inc.

Country where clinical trial is conducted

United States, 

Outcome

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