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

NCT02651727 | Terminated Phase 1

• 1 other identifier: VS-4718-103
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 2

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.

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• 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]

• 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

Study Arms (3)

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

EXPERIMENTAL

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

Part B, Cohort 2- VS-4718, nab-paclitaxel, gemcitabine

EXPERIMENTAL

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

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

Part A- VS-4718, nab-paclitaxel, gemcitabine

EXPERIMENTAL

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.

Drug: Part A- VS-4718, nab-paclitaxel, gemcitabine

Interventions

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

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 1- VS-4718, nab-paclitaxel, gemcitabine

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

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 B, Cohort 2- VS-4718, nab-paclitaxel, gemcitabine

Part A- VS-4718, nab-paclitaxel, gemcitabine DRUG

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 A- VS-4718, nab-paclitaxel, gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Verastem, Inc.: lead

Study Sites (2)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Gettysburg Cancer Center

Gettysburg, Pennsylvania, 17325, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

130-nm albumin-bound paclitaxel; Gemcitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Hagop Youssoufian, MD

  Verastem, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2016
• First Posted: January 11, 2016
• Study Start: September 1, 2015
• Primary Completion: January 1, 2017
• Study Completion: January 1, 2017
• Last Updated: July 27, 2017

Record last verified: 2017-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)