Phase I/Ib Study of Paclitaxel in Combination With VS-6063 in Patients With Advanced Ovarian Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Verastem, Inc.
ClinicalTrials.gov Identifier:
NCT01778803
First received: January 22, 2013
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

This is a Phase I/Ib, open-label, multicenter, dose-escalation trial of paclitaxel in combination with defactinib (VS-6063), a focal adhesion kinase inhibitor, in patients with advanced ovarian cancer. This clinical study is comprised of 2 parts: Phase I (Dose Escalation) and Phase Ib (Expansion). The purpose of this study is to assess assess the safety (including the recommended phase 2 dose), the pharmacokinetics, and the anti-cancer activity of defactinib (VS-6063) when administered in combination with paclitaxel. Pharmacodynamic effects will also be examined in tumor biopsies.


Condition Intervention Phase
Ovarian Cancer
Drug: defactinib (VS-6063)
Drug: Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/Ib Study of Paclitaxel in Combination With VS-6063, a Focal Adhesion Kinase Inhibitor, in Subjects With Advanced Ovarian Cancer

Resource links provided by NLM:


Further study details as provided by Verastem, Inc.:

Primary Outcome Measures:
  • Assess the safety and tolerability of defactinib (VS-6063) when administered in combination with paclitaxel in subjects with advanced ovarian tumors [ Time Frame: From start of treatment to end of treatment, an expected average of 12 weeks ] [ Designated as safety issue: Yes ]
    Adverse events and their frequency, duration and severity, physical examination, laboratory parameters, vital signs and ECG change monitoring as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03

  • Establish the recommended phase 2 dose (RP2D) of defactinib (VS-6063) in combination with paclitaxel in subjects with advanced ovarian tumors [ Time Frame: From start of treatment to end of cycle 1 (4 week cycles) ] [ Designated as safety issue: Yes ]
    The RP2D will be determined based on the maximum tolerated dose (MTD) of defactinib (VS-6063) in combination with paclitaxel as determined by number of participants with dose limiting toxicities (DLTs) related to defactinib in combination with paclitaxel


Secondary Outcome Measures:
  • Evaluate the efficacy of subjects treated with paclitaxel and defactinib (VS-6063) [ Time Frame: Every 2 cycles up to end of treatment, an expected average of 12 weeks ] [ Designated as safety issue: No ]
    Response rate and progression-free survival, as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1

  • Assess the pharmacokinetics (PK) of defactinib (VS-6063) when co-administered with paclitaxel [ Time Frame: Time points at Day 1 and Day 15 in Cycle 1 ] [ Designated as safety issue: No ]
    PK parameters, including but not limited to plasma concentration, AUC (Area Under Curve) 0-t, Cmax, Tmax, and T1/2


Other Outcome Measures:
  • Evaluate biomarkers of defactinib (VS-6063) activity [ Time Frame: Day 1 and Day 10 of treatment ] [ Designated as safety issue: No ]
    Pre and post dose biomarkers (including but not limited to FAK and phospho-FAK, as well as specific markers for cell cycle inhibition, apoptosis and cancer stem cells) in archival tumor tissue and new biopsy samples

  • Examine if the tumor expression status correlates with response to defactinib (VS-6063) therapy [ Time Frame: From start of treatment to end of treatment, an expected average of 12 weeks ] [ Designated as safety issue: No ]
    Tumor expression status (pFAK and other biomarkers) compared with response to defactinib, as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1


Estimated Enrollment: 27
Study Start Date: January 2013
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: defactinib (VS-6063) plus paclitaxel
Oral defactinib (VS-6063) administered twice daily, in combination with intravenous paclitaxel administered on Days 1, 8, and 15 of a 28 day cycle.
Drug: defactinib (VS-6063) Drug: Paclitaxel
Other Name: Taxol

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able to provide signed and dated informed consent prior to initiation of any study procedures.
  2. Female subjects aged ≥ 18 years.
  3. Advanced or refractory ovarian cancer, confirmed histologically.
  4. Subjects may have received up to 4 prior lines of chemotherapy for their metastatic disease.
  5. All persistent clinically significant toxicities from prior chemotherapy must be ≤ Grade 1.
  6. ECOG performance status of 0 or 1 (refer to Appendix A), measured within 72 hours before the start of treatment.
  7. Predicted life expectancy of ≥ 3 months.
  8. Adequate renal function [creatinine ≤ 1.5x ULN (upper limit of normal)] or GFR of ≥ 50mL/min.
  9. Adequate hepatic function (total bilirubin ≤ 1.5x ULN for the institution; AST [aspartate transaminase] and ALT [alanine transaminase] ≤ 3x ULN, or ≤ 5x ULN if due to liver involvement by tumor).
  10. Adequate bone marrow function (hemoglobin ≥ 9.0 g/dL; platelets≥ 100 x109cells/L; absolute neutrophil count ≥ 1.5x109 cells/L).
  11. Corrected QT interval (QTc) < 470 ms (as calculated by the Fridericia correction formula).
  12. Negative pregnancy test for females of child-bearing potential; must be surgically sterile, postmenopausal, or willing and able to be compliant with a contraceptive regimen (double barrier birth control) during and for 3 months after the treatment period.
  13. Willing and able to participate in the trial and comply with all trial requirements.

Exclusion Criteria:

  1. Gastrointestinal (GI) condition which could interfere with the swallowing or absorption of study medication.
  2. Uncontrolled or severe concurrent medical condition (including uncontrolled brain metastases). Stable brain metastases either treated or being treated with a stable dose of steroids/anticonvulsants, with no dose change within 28 days prior to the first dose of study drug, will be allowed.
  3. History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.
  4. Known history of Gilbert's Syndrome.
  5. Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug.
  6. Subjects with known infection with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) (testing not required).
  7. Subjects with Hepatitis A, B or C (testing not required).
  8. Subjects being actively treated for a secondary malignancy.
  9. Cancer-directed therapy (chemotherapy, radiotherapy, hormonal therapy, biologic or immunotherapy, etc.) within 28 days of the first dose of study drug or 5 half-lives, whichever is shorter.
  10. Major surgery within 28 days prior to the first dose of study drug.
  11. Use of an investigational drug within 28 days or 5 half-lives (whichever is shorter) prior to the first dose of study drug. A minimum of 10 days between termination of the investigational drug and administration of the study treatment is required. In addition, any drug-related toxicity except alopecia should have recovered to grade 1 or less.
  12. Pregnant or breastfeeding.
  13. Any evidence of serious active infections.
  14. Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis.
  15. Uncontrolled intercurrent illness including symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01778803

Locations
United States, Florida
Florida Cancer Specialists
Sarasota, Florida, United States
United States, Oklahoma
University of Oklahoma
Oklahoma City, Oklahoma, United States
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
Sponsors and Collaborators
Verastem, Inc.
Investigators
Study Director: Mitchell Keegan, PhD Verastem, Inc.
  More Information

No publications provided

Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT01778803     History of Changes
Other Study ID Numbers: VS-6063-101
Study First Received: January 22, 2013
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 22, 2014