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

• ClinicalTrials.gov Identifier: NCT00719875
• Recruitment Status: Completed
• First Posted: July 22, 2008
• Last Update Posted: March 3, 2017
• Sponsor: Yale University
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Yale University

Tracking Information

• First Submitted Date: July 18, 2008
• First Posted Date: July 22, 2008
• Last Update Posted Date: March 3, 2017
• Study Start Date: December 2008
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 18, 2008): 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 ]
• Original Primary Outcome Measures: Same as current
• Current Secondary Outcome Measures (submitted: July 18, 2008): 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 ]
• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced Breast Cancer

Intervention

Drug: Vorinostat

BID days -7, 1-7 and 15-21, 200 mg

Other Names:

• SAHA
• Zolinza
• HDAC inhibitor
• suberoylanilide hydroxamic acid

Study Arms

Experimental: 1

Intervention: Drug: Vorinostat

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 1, 2017): 24
• Original Estimated Enrollment (submitted: July 18, 2008): 47
• Actual Study Completion Date: June 2013
• Actual Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)

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:

  • 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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00719875
• Other Study ID Numbers: 0803003591
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Yale University
• Original Responsible Party: Maysa Abu-Khalaf, M.D., Yale University School of Medicine
• Current Study Sponsor: Yale University
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC

Investigators

• Principal Investigator: Maysa Abu-Khalaf, M.D.; Yale Unviversity School of Medicine

• PRS Account: Yale University
• Verification Date: March 2017