Phase Ib/II Neoadjuvant Trial of the Farnesyltransferase Inhibitor, R115777 With Docetaxel and Capecitabine for Patients With Stage IIIA or IIIB Breast Cancer
I. Determine the maximum tolerated dose and recommended dose of capecitabine in combination
with docetaxel and tipifarnib in patients with locally advanced or metastatic solid tumors.
(Phase Ib) II. Determine the complete pathological and clinical response rate in patients
with stage IIIA or IIIB breast cancer treated with this regimen. (Phase II)
I. Determine the toxicity of this regimen in these patients. II. Determine disease-free and
overall survival of patients treated with this regimen.
OUTLINE: This is a multicenter, dose-escalation study of capecitabine. Patients in phase II
are stratified according to type of breast cancer (inflammatory vs noninflammatory).
Phase Ib: Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on
days 1-14 and docetaxel IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days
in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
Phase II: Patients receive oral tipifarnib twice daily for 6 days. Beginning at least 48
hours after completion of the initial dose of tipifarnib, patients receive treatment as in
phase Ib for up to 6 courses at the MTD of capecitabine. Patients in phase Ib are followed
at 3 months.
Patients in phase II are followed every 4 months for up to 5 years.
PROJECTED ACCRUAL: A total of 24-53 patients (9-18 for phase Ib and 15-35 for phase II) will
be accrued for this study within 14-35 months.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Dose-limiting toxicity (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 (Phase I)
United States: Food and Drug Administration
|Mayo Clinic||Rochester, Minnesota 55905|
|Barbara Ann Karmanos Cancer Institute||Detroit, Michigan 48201|
|Washington University School of Medicine||Saint Louis, Missouri 63110|
|Mayo Clinic in Arizona||Scottsdale, Arizona 85259-5404|
|Mayo Clinic in Florida||Jacksonville, Florida 32224|
|University of Wisconsin Medical School||Madison, Wisconsin 53792-0001|
|Howard University Cancer Center CCOP||Washington, District of Columbia 20060|