Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097, Paclitaxel, and Carboplatin Before Surgery in Treating Patients With Stage II or Stage III Triple-Negative Breast Cancer
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|ClinicalTrials.gov Identifier: NCT01238133|
Recruitment Status : Terminated
First Posted : November 10, 2010
Last Update Posted : September 4, 2015
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor Negative HER2/Neu Negative Progesterone Receptor Negative Stage IIA Breast Cancer Stage IIB Breast Cancer Stage IIIA Breast Cancer Stage IIIB Breast Cancer Stage IIIC Breast Cancer Triple-Negative Breast Carcinoma||Drug: Carboplatin Drug: Gamma-Secretase Inhibitor RO4929097 Other: Laboratory Biomarker Analysis Drug: Paclitaxel Other: Pharmacological Study Procedure: Therapeutic Conventional Surgery||Phase 1|
I. To determine the maximum-tolerated dose (MTD) and dose limiting toxicity (DLT) of RO4929097 (gamma-secretase 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 area under the plasma-concentration time curve (AUC)0-24hr 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 weekly paclitaxel and every 3 weeks carboplatin in patients with stage II-III TNBC.
II. To measure real-time pharmacokinetics of paclitaxel when administered in combination with RO4929097 (3 days on, 4 days off) and every 3 weeks carboplatin in patients with stage II-III TNBC.
III. To evaluate the rate of pathologic and clinical complete response to the treatment with combination of RO492097, paclitaxel, and carboplatin in patients with clinical stage II-III TNBC.
OUTLINE: This is a dose-escalation study of gamma secretase inhibitor RO4929097 (RO4929097).
Patients receive gamma-secretase inhibitor RO4929097 orally (PO) once daily (QD) on days 1-3, 8-10, and 15-17, paclitaxel intravenously (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.
After completion of study treatment, patients are followed up for 1 year.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||December 2010|
|Actual Primary Completion Date :||January 2014|
|Actual Study Completion Date :||August 2015|
Experimental: Treatment (RO4929097, paclitaxel, carboplatin, surgery)
Patients receive gamma-secretase inhibitor RO4929097 PO QD 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.
Other Names:Drug: Gamma-Secretase Inhibitor RO4929097
Other Name: RO4929097Other: Laboratory Biomarker Analysis
Correlative studiesDrug: Paclitaxel
Other Names:Other: Pharmacological Study
Ancillary studiesProcedure: Therapeutic Conventional Surgery
- Incidence of adverse events of gamma-secretase inhibitor RO4929097 as assessed by CTCAE v 4.0 [ Time Frame: Up to 1 year ]
- MTD of gamma-secretase inhibitor RO4929097 based on DLT as assessed by CTCAE version (v) 4.0 [ Time Frame: 21 days ]Analysis will consist of descriptive statistics only. Frequency will be computed for discrete variables with 95% confidence intervals for the proportion.
- Pharmacokinetic parameters of gamma-secretase inhibitor RO4929097 and paclitaxel [ Time Frame: At baseline, at 30, 55, 70 and 90 minutes, and 2, 3, 4, 6, 8 and 24 hours of days 1, 8, 15, and 17 of course 1 ]AUC0-24hrs, clearance, maximum concentration, and maximum time (for gamma-secretase inhibitor RO4929097 only) when each drug is administered alone versus when they are co-administered will be compared. Only descriptive statistics will be provided.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01238133
|United States, Ohio|
|Ohio State University Comprehensive Cancer Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||Ewa Mrozek||Ohio State University Comprehensive Cancer Center|