A Pilot Study of Vorinostat to Restore Sensitivity to Aromatase Inhibitor Therapy
I. Determine the rate of clinical benefit (objective response plus stable disease) for
patients treated with cycles consisting of 2 weeks of vorinostat followed by 6 weeks of AI
I. Assess the safety and tolerability of vorinostat in patients with metastatic breast
II. Assess the change in estrogen receptor (ER) expression, measured as the change in
fluoroestradiol standard uptake value (FES SUV) using fluoroestradiol-positron emission
tomography (FES-PET) completed per protocol 7184 after two weeks of vorinostat therapy and
after 8 weeks of therapy.
III. Assess tumor metabolic response, measured as the change in fluorodeoxyglucose (FDG) SUV
using FDG PET completed per protocol 7184 after two weeks of vorinostat 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), epithelial growth factor receptor (EGFR),
vascular endothelial growth factor (VEGF) tumor expression after two weeks of vorinostat
therapy in patients that consent to optional tissue biopsy procedure.
VI. Assess the time to progression and the overall survival of patients treated with cycles
of 2 weeks of vorinostat followed by 6 weeks of AI.
Patients receive vorinostat orally (PO) once daily (QD) for 2 weeks followed by AI therapy
comprising anastrozole PO QD, letrozole PO QD, OR exemestane PO QD for 6 weeks. Courses
repeat every 8 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 2 years,
every 6 months until disease progression, and then annually thereafter.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Rate of clinical benefit
A 95% score (Wilson) confidence interval will be computed for the response rate and the rate of clinical benefit. The radiological (by computed tomography [CT]) response rate of vorinostat will be determined by tumor measurements assessed by modified RECIST criteria.
Up to approximately 5 years
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Institutional Review Board
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium||Seattle, Washington 98109|