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
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
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase II dose of tipifarnib when combined with weekly sequential paclitaxel (phase I)
Montefiore Medical Center
United States: Food and Drug Administration
|Albert Einstein College of Medicine||Bronx, New York 10461|
|H. Lee Moffitt Cancer Center and Research Institute||Tampa, Florida 33612|
|Weill Medical College of Cornell University||New York, New York 10021|
|Mount Sinai Medical Center||New York, New York 10029|
|Montefiore Medical Center||Bronx, New York 10467-2490|
|M D Anderson Cancer Center||Houston, Texas 77030|
|Columbia University Medical Center||New York, New York 10032|