A Dose-escalating and Phase II Clinical Trial of the Histone Deacetylase (HDAC) Inhibitor Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA, ZolinzaTM) in Combination With Capecitabine (XelodaTM) Using a New Weekly Dose Regimen for Advanced Breast Cancer

Yale University1 site in 1 country24 target enrollmentDecember 2008

ConditionsAdvanced Breast Cancer

InterventionsVorinostat

DrugsVorinostat

Overview

Phase: Phase 1
Intervention: Vorinostat
Conditions: Advanced Breast Cancer
Sponsor: Yale University
Enrollment: 24
Locations: 1
Primary Endpoint: To determine the safety, dose-limiting toxicities and maximum tolerated dose of oral capecitabine in combination with oral vorinostat given twice a day and to determine the objective response rate using RECIST criteria
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to determine the safety profile, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), of oral vorinostat in combination with oral capecitabine given on days 1-7 and 15-21 of a 28 day cycle in patients with advanced breast cancer, using RECIST criteria.

This study was originally intended to be a phase 1/phase 2. The protocol was amended to make this study a phase 1 only.

Registry

clinicaltrials.gov

Start Date

December 2008

End Date

June 2013

Last Updated

9 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Yale University

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must have histologically confirmed advanced breast cancer
•For the dose escalation phase: Patients must be refractory to standard therapy or for which no curative standard therapy exists, to be considered.
•For the phase II: Patients with histologically confirmed metastatic breast cancer who have had no more than 2 prior chemotherapy regimens for treatment of their metastatic breast cancer.
•Metastatic disease should not be progressing so as to require palliative treatment within 4 weeks of enrollment based on clinical assessment by the investigator.
•Development of new lesions or an increase in preexisting lesions on bone scintigraphy, CT, MRI or by physical examination. Patients in whom the sole criterion for progression is an increase in a biochemical marker, e.g., carcinoembryonic antigen (CEA), or an increase in symptoms, are not eligible.
•No radiotherapy, treatment with cytotoxic agents, or treatment with biologic agents within the 4 weeks prior to beginning treatment on this study (6 weeks for mitomycin or nitrosoureas). At least 2 weeks must have elapsed from any prior surgery or hormonal therapy. Patients must have fully recovered from the acute toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment). Patients with persisting, stable chronic toxicities from prior treatment ≤ grade 1 are eligible.
•Age ≥18 years.
•ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A).
•Life expectancy of greater than 3 months
•Patients must have normal organ and marrow function as defined below:

Exclusion Criteria

•Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
•Patients may not be receiving any other investigational agents.
•Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or capecitabine.
•Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
•Women that are pregnant or breast-feeding are excluded from this study.
•HIV-positive patients are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy and the potential pharmacokinetic interaction between antiretroviral therapy and the investigational agents.
•Patient had prior treatment with an HDAC inhibitor. Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period.

Arms & Interventions

1

Intervention: Vorinostat

Outcomes

Primary Outcomes

To determine the safety, dose-limiting toxicities and maximum tolerated dose of oral capecitabine in combination with oral vorinostat given twice a day and to determine the objective response rate using RECIST criteria

Time Frame: Upon completion of study

Secondary Outcomes

To determine the clinical benefit, time to progression, and duration of response, in patients with metastatic breast cancer treated with this combination(Upon completion of study)