Clinical Trial: Ixabepilone and Vorinostat in Treating Patients With Metastatic Breast Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase I Trial of Ixabepilone and Vorinostat in Metastatic Breast Cancer

Brief Summary:

RATIONALE: Drugs used in chemotherapy, such as ixabepilone, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing or by stopping them from spreading. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving ixabepilone together with vorinostat may kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects, best way to give, and best dose of vorinostat when given together with ixabepilone in treating patients with breast cancer that has spread to another place in the body.


Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of the combination of vorinostat with ixabepilone.

II. To determine the best schedule for delivery of this drug combination. III. To recommend a phase II dose of vorinostat in combination with ixabepilone.

SECONDARY OBJECTIVES:

I. To determine the objective response rate and/or clinical benefit rate. II. To assess the toxicity profile.

TERTIARY OBJECTIVES:

I. Collecting circulating tumor cells pre and post-treatment to study its deoxyribonucleic acid (DNA) somatic mutation and methylation assay after the introduction of histone deacetylases (HDAC) inhibitors and ixabepilone.

II. To determine whether administration of vorinostat with ixabepilone will alter the pharmacokinetics of vorinostat.

OUTLINE: This is a phase I, dose-escalation study of vorinostat. Patients are randomized to 1 of 2 treatment arms.

Arm I (Cohort A): Patients receive oral vorinostat once daily on days 1-14 and ixabepilone intravenously (IV) over 3 hours on day 2. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Arm II (Cohort B): Patients receive oral vorinostat once daily on days 1-7 and 15-21. Patients also receive ixabepilone IV over 3 hours on days 2, 9, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients ar
Sponsor: City of Hope Medical Center

Current Primary Outcome: Dose limiting toxicity defined as any treatment-related grade 3 or greater non-hematologic toxicity, grade 4 febrile neutropenia, thrombocytopenia or grade 4 neutropenia as a result of unresolved toxicity [ Time Frame: Cohort A evaluated every 3 weeks during treatment, Cohort B every 4 weeks during treatment. ]

Graded according to the National Cancer Institute (NCI) CTCAE version 4.0. DLT is defined for each dose level and will include both drugs ixabepilone and vorinostat.


Original Primary Outcome: Dose limiting toxicity [ Time Frame: Cohort A every 3 weeks during treatment, Cohort B every 4 weeks during treatment. ]

Current Secondary Outcome:

  • Objective response rate and/or clinical benefit rate [ Time Frame: Cohort A evaluated every 6 weeks, Cohort B evaluated every 8 weeks until progression of disease. ]
  • Toxicity profile [ Time Frame: Cohort A every 3 weeks during treatment, Cohort B every 4 weeks during treatment. ]


Original Secondary Outcome: Same as current

Information By: City of Hope Medical Center

Dates:
Date Received: March 8, 2010
Date Started: May 17, 2010
Date Completion: June 2018
Last Updated: April 4, 2017
Last Verified: April 2017