This pilot clinical trial studies vorinostat in treating patients with stage IV breast cancer receiving hormone therapy. Vorinostat may help hormone therapy work better by making tumor cells more sensitive to the drug.
PRIMARY OBJECTIVES: I. Estimate the rate of clinical benefit (objective response plus stable disease) for patients treated with 28-day cycles of vorinostat (first 5 consecutive days each week for day 1-21) concurrent with daily aromatase inhibitor (AI) therapy (all 28 days). SECONDARY OBJECTIVES: I. Assess the safety and tolerability of vorinostat and AI combination therapy in patients with metastatic breast cancer. II. Assess the change in estrogen receptor (ER) expression, measured as the change in F-18 16 alpha-fluoroestradiol (FES) standardized uptake value (SUV) using FES positron emission tomography (PET) completed per protocol 7184 after two weeks of vorinostat and AI therapy and after 8 weeks of therapy. III. Assess tumor metabolic response, measured as the change in fludeoxyglucose F 18 (FDG) SUV using FDG PET completed per protocol 7184 after two weeks of vorinostat and AI therapy and after 8 weeks of therapy. IV. Assess the change in hormone levels (estradiol, estrone, follicle-stimulating hormone \[FSH\], sex binding globulin, testosterone, and free testosterone) after 8 weeks of therapy. V. Assess the change in ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) tumor expression after two weeks of vorinostat and AI therapy in patients that consent to optional tissue biopsy procedure. VI. Assess the time to progression and the overall survival of patients treated with 28-day cycles of vorinostat (first 5 consecutive days each week for day 1-21) concurrent with daily AI therapy (all 28 days). OUTLINE: Patients receive vorinostat orally (PO) 5 days a week for 3 weeks. Patients also receive AI therapy comprising either anastrozole PO daily, letrozole PO daily, or exemestane PO daily for 4 weeks. Courses repeat every 28 days in the absence of disease progression and unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years, then every 6 months until progression, and then annually thereafter.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States
Rate of Clinical Benefit of Patients Receiving Vorinostat/AI Combination Therapy According to RECIST
A 90% score (Wilson) confidence interval will be computed for the rate of clinical benefit. Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).
Time frame: 8 weeks
Response Rate According to RECIST
A 90% score (Wilson) confidence interval will be computed for the response rate. Clinical benefit according to Recist score is defined as: Stable Disease, Partial Remission or Complete Remission. Lack of clinical benefit is defined as Progressive Disease (increase in target lesion size by 20% or more).
Time frame: 8 weeks
Duration of Response
Duration of response will be summarized for responders.
Time frame: Up to 5 years
Progression-free Survival (PFS)
Progression-free survival is assessed relative to the start of the study therapy. Progression can be determined by RECIST 1.1, elevated tumor markers, worsening clinical symptoms or new lesions identified by FDG-PET or bone scan.
Time frame: From the time of start of study therapy to documented progression - up to 5 years
Overall Survival
Overall survival is assessed relative to the start of the study therapy to the date of death, from any cause.
Time frame: From the time of start of study therapy to date of documented death
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Given PO
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