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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

Phase 1/Phase 2
18 Years
Open (Enrolling)
Advanced Breast Cancer

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Trial Information

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

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

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

- 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

- 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.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

Upon completion of study

Safety Issue:


Principal Investigator

Maysa Abu-Khalaf, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

Yale Unviversity School of Medicine


United States: Institutional Review Board

Study ID:




Start Date:

December 2008

Completion Date:

December 2010

Related Keywords:

  • Advanced Breast Cancer
  • Breast Neoplasms



Yale University School Of Medicine New Haven, Connecticut  06520