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Trial record 1 of 1 for:    NCT02651727
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Ph 1 Study of VS-4718, a FAK Inhibitor, in Combination With Nab-paclitaxel and Gemcitabine in Advanced Cancer Subjects

This study has been terminated.
(the company's decision to de-prioritize 4718 development)
Sponsor:
ClinicalTrials.gov Identifier:
NCT02651727
First Posted: January 11, 2016
Last Update Posted: July 27, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Verastem, Inc.
  Purpose
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.

Condition Intervention Phase
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 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Verastem, Inc.:

Primary Outcome Measures:
  • Incidence of dose-limiting toxicities (DLTs) [ Time Frame: 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:
  • 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) [ Time Frame: 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 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 ]
  • 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 ]

Enrollment: 13
Study Start Date: September 2015
Study Completion Date: January 2017
Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 on Day 1 of Cycle 3
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 2. The starting dose of VS-4718 will be 200 mg BID.
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 2. The starting dose of VS-4718 will be 200 mg BID.

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
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02651727


Locations
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Pennsylvania
Gettysburg Cancer Center
Gettysburg, Pennsylvania, United States, 17325
Sponsors and Collaborators
Verastem, Inc.
Investigators
Study Chair: Hagop Youssoufian, MD Verastem, Inc.
  More Information

Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT02651727     History of Changes
Other Study ID Numbers: VS-4718-103
First Submitted: January 6, 2016
First Posted: January 11, 2016
Last Update Posted: July 27, 2017
Last Verified: January 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Paclitaxel
Gemcitabine
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs


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