Tipifarnib and Combination Chemotherapy in Treating Patients With Stage II or Stage III Breast Cancer
Male Breast Cancer
Stage II Breast Cancer
Stage IIIA Breast Cancer
Stage IIIB Breast Cancer
Stage IIIC Breast Cancer
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I-II Study of R115777 (Tipifarnib, Zarnestra®) Plus Sequential Weekly Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide in Patients With Stage IIB-IIIC Breast Cancer|
- Recommended Phase II Dose of Tipifarnib When Combined With Weekly Sequential Paclitaxel (Phase I) [ Time Frame: 2 weeks ] [ Designated as safety issue: Yes ]
- Pathologic Complete Response Rate (pCR) Evaluated Using RECIST (Phase II) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]An increase in the breast pCR from 15% (anticipated for chemotherapy alone) to 35% would be considered promising.
|Study Start Date:||April 2007|
|Study Completion Date:||September 2013|
|Primary Completion Date:||September 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm I
Tipifarnib plus sequential weekly paclitaxel followed by doxorubicin plus cyclophosphamide
Other Names:Drug: paclitaxel
Other Names:Drug: doxorubicin
Other Names:Drug: cyclophosphamide
I. To determine the recommended phase II dose of tipifarnib when given together with paclitaxel in patients with stage IIB-IIIC breast cancer. (Phase I) II. To determine the pathologic complete remission rate (including breast and breast plus axillary nodes) in patients treated with sequential paclitaxel and tipifarnib followed by dose-dense doxorubicin hydrochloride, cyclophosphamide, and tipifarnib. (Phase II) III. To determine the feasibility and safety of this regimen in these patients. (Phase I and II)
OUTLINE: This is a multicenter, phase I, dose-escalation study of tipifarnib followed by a phase II study.
PHASE I: Paclitaxel plus tipifarnib: Patients receive paclitaxel IV over 1 hour on day 1 and oral tipifarnib twice daily on days 1-3.
Treatment repeats weekly for 12 courses in the absence of disease progression or unacceptable toxicity. Patients with no evidence of disease progression after 12 courses proceed to AC chemotherapy plus tipifarnib. Cohorts of 3-6 patients receive escalating doses of tipifarnib until the recommended phase II dose (RTPD) is determined. The RTPD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
AC chemotherapy plus tipifarnib: Patients receive doxorubicin hydrochloride IV over 5-10 minutes and cyclophosphamide IV over 30-60 minutes on day 1, oral tipifarnib twice daily on days 2-7, and pegfilgrastim subcutaneously on day 2.
Treatment repeats every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
PHASE II: Patients receive paclitaxel and tipifarnib at the RTPD and AC chemotherapy plus tipifarnib as in phase I. After completion of AC plus tipifarnib (in both phases), patients are re-evaluated for surgery (i.e., modified radical mastectomy, radical mastectomy, segmental mastectomy or lumpectomy with an axillary lymph node dissection).
After completion of study treatment, patients are followed every 6 months for 5 years and then annually for 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00470301
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|United States, New York|
|Albert Einstein College of Medicine|
|Bronx, New York, United States, 10461|
|Montefiore Medical Center|
|Bronx, New York, United States, 10467-2490|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|Mount Sinai Medical Center|
|New York, New York, United States, 10029|
|Weill Medical College of Cornell University|
|New York, New York, United States, 10065|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Dawn Hershman||Montefiore Medical Center|