HDAC Inhibitor Vorinostat (SAHA) With Capecitabine (Xeloda) Using a New Weekly Dose Regimen for Advanced Breast Cancer

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by Yale University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Yale University
ClinicalTrials.gov Identifier:
NCT00719875
First received: July 18, 2008
Last updated: June 5, 2009
Last verified: June 2009
  Purpose

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.


Condition Intervention Phase
Advanced Breast Cancer
Drug: Vorinostat
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the clinical benefit, time to progression, and duration of response, in patients with metastatic breast cancer treated with this combination [ Time Frame: Upon completion of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 47
Study Start Date: December 2008
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Vorinostat
BID days -7, 1-7 and 15-21, 200 mg
Other Names:
  • SAHA
  • Zolinza
  • HDAC inhibitor
  • suberoylanilide hydroxamic acid

  Eligibility

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

    • leukocytes ≥3,000/mcL
    • absolute neutrophil count ≥1,500/mcL
    • platelets ≥100,000/mcL
    • total bilirubin within normal institutional limits
    • AST(SGOT)/ALT(SGPT) ≤2.5 X institutional upper limit of normal
    • creatinine within normal institutional limits OR
    • creatinine clearance ≥60 mL/min/1.73 m² for patients with creatinine levels above institutional normal.
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.

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.
  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: NCT00719875

Contacts
Contact: Mary Beth Clark 203-785-6822 mary.clark@yale.edu

Locations
United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06219
Principal Investigator: Maysa Abu-Khalaf, M.D.         
Sponsors and Collaborators
Yale University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Maysa Abu-Khalaf, M.D. Yale Unviversity School of Medicine
  More Information

No publications provided

Responsible Party: Maysa Abu-Khalaf, M.D., Yale University School of Medicine
ClinicalTrials.gov Identifier: NCT00719875     History of Changes
Other Study ID Numbers: 0803003591
Study First Received: July 18, 2008
Last Updated: June 5, 2009
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Vorinostat
Histone Deacetylase Inhibitors
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014