A Phase I Dose Escalation Trial of RO4929097 Administered in Combination With Exemestane in Pre- and Postmenopausal Patients With ER + Metastatic Breast Cancer / A Randomized Phase II Trial Comparing Exemestane in Combination With RO4929097 Compared With Exemestane Alone as Second or Third Line Hormonal Treatment of ER + Metastatic Breast Cancer in Pre- and Post-Menopausal Patients
I. Determine the maximum-tolerated dose or the recommended phase II dose of gamma-secretase
inhibitor RO4929097 (RO4929097) in combination with exemestane in pre- and postmenopausal
patients with estrogen receptor-positive (ER+) advanced or metastatic breast cancer.
II. Determine the safety and tolerability of this regimen in these patients. III. Determine
the progression-free survival of patients treated with exemestane with vs without RO4929097.
I. Determine the overall tumor response rate in patients treated with these regimens.
II. Determine the overall survival of patients treated with these regimens. III. Determine
the safety of these regimens in these patients. IV. Determine the quality of life of
patients treated with these regimens. V. Identify biomarkers of response to treatment or
OUTLINE: This is a multicenter, phase I, dose-escalation study of gamma-secretase inhibitor
RO4929097 followed by a randomized phase II study.
Patients receive oral exemestane once daily on days 1-21 and oral gamma-secretase inhibitor
RO4929097 once daily on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the
absence of disease progression or unacceptable toxicity.
PHASE II: Patients are stratified according to menopausal status (pre- vs postmenopausal)
and visceral disease (yes vs no). Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients receive exemestane as in phase I and oral gamma-secretase inhibitor
RO4929097 at the MTD determined in phase I. Courses repeat every 21 days in the absence of
disease progression or unacceptable toxicity.
ARM II: Patients receive exemestane as in arm I. Courses repeat every 21 days in the absence
of disease progression or unacceptable toxicity.
In addition to exemestane, pre-menopausal patients receive goserelin subcutaneously every 28
days. Patients may undergo blood and tissue sample collection for correlative studies.
Patients may complete quality-of-life questionnaires at baseline and periodically during
study using the Functional Assessment of Cancer Therapy for Breast Cancer (FACT-B).
After completion of study therapy, patients are followed up for 4 weeks and then every 6
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Incidence of treatment emergent adverse events (TEAEs) based on CTCAE version 3 grade (Phase I)
Will be summarized by body system, preferred term, verbatim of adverse event, intensity, and relationship to each study drug (BMS-936558 and/or the peptide vaccine).
Up to 70 days
H. Lee Moffitt Cancer Center and Research Institute
United States: Food and Drug Administration
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Vanderbilt University||Nashville, Tennessee 37232-6305|
|University of North Carolina||Chapel Hill, North Carolina 27599|
|Emory University||Atlanta, Georgia 30322|