A Pilot Study of Vorinostat to Restore Sensitivity to Aromatase Inhibitor Therapy Part B
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.
Interventional
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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.
Up to 5 years
No
Hannah Linden
Principal Investigator
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
United States: Food and Drug Administration
7841
NCT01720602
November 2012
Name | Location |
---|---|
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle, Washington 98109 |