A Phase 1 Study of Neoadjuvant Chemotherapy With The Gamma Secretase Inhibitor RO4929097 in Combination With Paclitaxel And Carboplatin In Patients With Clinical Stage II-III Triple Negative Breast Cancer
I. To determine the maximum-tolerated dose (MTD) and dose limiting toxicity (DLT) of
RO4929097 (gamma-secretase/Notch signalling pathway inhibitor RO4929097) given 3 days on, 4
days off in combination with weekly paclitaxel and every 3 weeks carboplatin that will not
cause a 30% or more decrease in paclitaxel AUC0-24hr on day 15 compared to day-1 in patients
with clinical stage II-III triple negative breast cancer (TNBC).
I. To measure real-time pharmacokinetics of RO4929097 when administered in combination with
paclitaxel and carboplatin in patients with stage II or III TNBC.
II. To measure real-time pharmacokinetics of paclitaxel when administered in combination
with RO4929097 and carboplatin in patients with stage II or III TNBC.
III. To evaluate the rate of pathologic and clinical complete response to the combination of
RO492097, paclitaxel, and carboplatin in patients with clinical stage II or III TNBC.
OUTLINE: This is a dose-escalation study of gamma secretase inhibitor RO4929097 (RO4929097).
Patients receive oral gamma-secretase/Notch signalling pathway inhibitor RO4929097 once
daily on days 1-3, 8-10, and 15-17, paclitaxel IV over 60 minutes on days 1, 8, and 15 (day
-1 of course one), and carboplatin IV over 60 minutes on day 1. Treatment repeats every 21
days for 6 courses in the absence of disease progression or unacceptable toxicity. Within 4
weeks after completion of neoadjuvant therapy, patients undergo definitive breast surgery.
Patients undergo blood sample collection at baseline and periodically during study for
After completion of study therapy, patients are followed up for 1 year.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD of gamma-secretase/Notch signalling pathway inhibitor RO4929097 based on DLT as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0
Analysis will consist of descriptive statistics only. Frequency will be computed for discrete variables with 95% confidence intervals for the proportion.
Ohio State University
United States: Food and Drug Administration
|Ohio State University Medical Center||Columbus, Ohio 43210|