A Randomized Phase II Study of Fulvestrant vs. Fulvestrant in Combination With Bortezomib in Women With ER Positive Metastatic Breast Cancer
I. To determine if the addition of bortezomib to fulvestrant improves median progression
free survival (PFS) compared with fulvestrant alone in postmenopausal women with ER-positive
locally advanced inoperable or metastatic breast cancer who have disease that is resistant
to aromatase inhibitor therapy (Arms A vs. B).
I. To determine if the addition of bortezomib to fulvestrant improves the clinical benefit
rate (defined as objective response plus stable disease for at least 24 weeks from day+1).
II. To determine the percent of patients, treated with fulvestrant alone and fulvestrant
plus bortezomib, who remain progression-free 24 weeks from day+1 (Arms A vs. B).
III. To determine the overall survival of patients treated with fulvestrant alone and
fulvestrant plus bortezomib. (Arms A, B, C).
IV. To determine the adverse event profile in patients treated with fulvestrant alone and
fulvestrant plus bortezomib (Arms A, B, C).
V. To determine the clinical benefit rate at 12 and 24 weeks of fulvestrant plus bortezomib
in patients who have progressed on the fulvestrant alone arm and crossover to receive the
combination (Arm C).
I. To perform an exploratory analysis of the effects of bortezomib (plus fulvestrant) in
intratumoral nuclear/cytoplasmic ER ratio, unfolded protein response (BiP), apoptotis
(cleaved caspase 3, Bcl-2 phospho JNK in patients with tumors accessible to biopsy who
consent to optional post-treatment biopsy.
II. To determine with cyclin D1 expression in pretreatment tumor specimens (from metastatic
disease or the primary tumor if the former is not available) is predictive of clinical
benefit with fulvestrant-bortezomib.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive fulvestrant intramuscularly on day 1 (days -14, 1, and 15 of course
1 only). Courses repeat every 28 days in the absence of disease progression or unacceptable
toxicity. Patients with progressive disease may crossover to arm II.
Arm II: Patients receive fulvestrant as in arm I and bortezomib IV on days 1, 8, and 15
(beginning in course 2). Courses repeat every 28 days in the absence of disease progression
or unacceptable toxicity.
After completion of study therapy, patients are followed up every 3 months.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
The PFS distributions of the two treatment arms will be estimated by Kaplan-Meier. PFS distributions will be compared by an unstratified log-rank test.
From first treatment day until objective or disease progression or death from any cause, assessed up to 4 years
Montefiore Medical Center
United States: Food and Drug Administration
|Cleveland Clinic Foundation||Cleveland, Ohio 44195|
|Roswell Park Cancer Institute||Buffalo, New York 14263|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Beth Israel Medical Center||New York, New York 10003|
|Cancer Institute of New Jersey||New Brunswick, New Jersey 08901|
|Weill Medical College of Cornell University||New York, New York 10021|
|Maimonides Medical Center||Brooklyn, New York 11219|
|Mount Sinai Medical Center||New York, New York 10029|
|University of Connecticut||Farmington, Connecticut 06032|
|Case Western Reserve University||Cleveland, Ohio 44106|
|Yale University||New Haven, Connecticut 06520|
|Ohio State University Medical Center||Columbus, Ohio 43210|
|New York University Clinical Cancer Center||New York, New York 10016|
|Eastchester Center for Cancer Care||Bronx, New York 10469|
|The North Division of Montefiore Medical Center||Bronx, New York 10466|
|New York University Langone Medical Center||New York, New York 10016|
|Columbia University Medical Center||New York, New York 10032|
|Montefiore Medical Center-Weiler Division||Bronx, New York 10461|
|Maimonides Cancer Center-Breast Cancer Program||Brooklyn, New York 11220|
|Saint Luke's Roosevelt Hospital Center - Roosevelt Division||New York, New York 10019|