Dasatinib In Combination With Weekly Paclitaxel For Patients With Metastatic Breast Carcinoma CA 180 194
The purpose of this study is to find the highest dose of dasatinib that can be safely given to a patient when the drug is given in combination with the known anticancer drug paclitaxel. Paclitaxel is an established anti-cancer drug, used in the treatment of many cancers, and it is an approved treatment for breast cancer. Dasatinib has been approved by the Food and Drug Administration for use as a single therapy in another kind of cancer, but its use in breast cancer patients, and in combination with paclitaxel is investigational.
In this study, we will test the safety of dasatinib when given at different dose levels in combination with paclitaxel. We want to find out what effects, good and/or bad, it has on the patient and on metastatic breast cancer.
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase I-II Study of Dasatinib in Combination With Weekly Paclitaxel for Patients With Metastatic Breast Carcinoma|
- Phase I Portion: To determine the MTD of dasatinib when administered in combination with a fixed dose of weekly paclitaxel. [ Time Frame: conclusion of the phase I portion of the study ]
- Phase II Portion: To estimate efficacy (objective response rate; ORR; complete response (CR) + partial response (PR)) of dasatinib when administered in combination with weekly paclitaxel at the MTD established during the phase I portion of this trial. [ Time Frame: conclusion of the study ]
- Phase I Portion: To obtain preliminary data on the therapeutic activity of dasatinib when administered in combination with weekly paclitaxel. [ Time Frame: conclusion of the phase I portion of the study ]
- Phase II Portion: To obtain safety and tolerability of dasatinib when administered in combination with weekly paclitaxel. [ Time Frame: conclusion of the study ]
- Phase II: To estimate secondary efficacy endpoints of this combination including clinical benefit (CR+PR+SD > 6 months), time to tumor progression (TTP), progression free survival (PFS) and duration of response. [ Time Frame: conclusion of the study ]
- Phase II: To obtain exploratory tumor biomarker data: assays of p-SRC, VEGFR2 and Collagen Type IV in plasma, obtained at baseline and after 2 cycles of treatment (8 weeks), will be performed by enzyme-linked immunosorbent assay. [ Time Frame: conclusion of the study ]
- Phase II: To perform analysis of mRNA expression on the tumor specimens, for a gene expression profiling of the responders versus non-responders, in order to identify potential predictors of response to dasatinib. [ Time Frame: conclusion of the study ]
- Phase II: To collect circulating tumor cells (CTC) at baseline and after 2 cycles of treatment (8 weeks) [ Time Frame: conclusion of the study ]
- Phase II: Exploratory somatic gene mutations detection in archived tumor samples [ Time Frame: 2 years ]
|Study Start Date:||January 2009|
|Estimated Study Completion Date:||January 2018|
|Estimated Primary Completion Date:||January 2018 (Final data collection date for primary outcome measure)|
Experimental: dasatinib and paclitaxel
The phase I portion is a standard, three-patient per cohort, dose escalation schedule will be used. Between 6 and 54 patients will likely be necessary to determine the MTD of dasatinib in combination with weekly paclitaxel.
The phase II portion of this trial has a Simon two-stage design to determine the efficacy of dasatinib when administered in combination with paclitaxel.
Drug: Dasatinib and Paclitaxel
A treatment cycle will consist of 28 days, according to the following schedule:
Dasatinib 120MG PO once daily, Weekly paclitaxel 80 mg/m2 given intravenously over 1 hour on day 1, 8, and 15 of a 28 day cycle.
The trial will initially test the combination of weekly paclitaxel and dasatinib given PO, once daily , continuously. In case of 2 dose-limiting toxicities (DLT) in the first cohort (0), the next cohort will test dasatinib given with a different schedule, 5 days on and 2 days off, omitting dasatinib the day prior and the day of administration of paclitaxel.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00820170
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Monica Fornier, MD||Memorial Sloan Kettering Cancer Center|