A Phase II Trial of Capecitabine in Combination With the Farnesyltransferase Inhibitor, R115777 (Tipifarnib, Zarnestra) in Patients With Metastatic Breast Cancer
Overview
- Phase
- Phase 2
- Intervention
- tipifarnib
- Conditions
- Recurrent Breast Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 70
- Locations
- 1
- Primary Endpoint
- Objective response rate (PR+CR)
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
This phase II trial is studying how well giving capecitabine together with tipifarnib works in treating women with taxane-resistant metastatic breast cancer. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving capecitabine together with tipifarnib may kill more tumor cells
Detailed Description
PRIMARY OBJECTIVES: I. The primary objective of this study is to determine the response rate in patients with taxane-resistant metastatic breast cancer treated with capecitabine plus tipifarnib. SECONDARY OBJECTIVES: I. To evaluate toxicity in patients with taxane-resistant metastatic breast cancer treated with capecitabine plus tipifarnib. II. To evaluate progression free survival, time to treatment failure, and overall survival in patients with taxane-resistant metastatic breast cancer treated with capecitabine plus tipifarnib. OUTLINE: This is a multicenter study. Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 4 additional courses beyond documentation of CR. Patients are followed every 3 months for 2 years and then every 6 months for 1 year.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female patients with histologically confirmed adenocarcinoma of the breast with manifestations of metastatic progression
- •Patients must have at least one objective measurable disease parameter as defined by RECIST criteria; tumor measurements and evaluation of non-measurable sites must be performed within 4 weeks prior to registration
- •ECOG performance status 0-2
- •In order to be eligible for inclusion, patients must meet all of the following criteria with regard to prior cytotoxic therapy: (1) prior treatment with an anthracycline (e.g., doxorubicin, epirubicin) either in the adjuvant/neoadjuvant setting and/or for metastatic disease, (2) prior treatment with a taxane (i.e. paclitaxel, docetaxel) for metastatic disease, or relapse while receiving adjuvant taxane therapy (3) progressive disease while receiving taxane therapy or up to 30 days after receiving the last taxane dose, (4) no more than three prior cytotoxic regimens for metastatic disease, (5) no prior treatment with capecitabine or 5-flourouracil for metastatic disease
- •Prior hormonal therapy in either the metastatic or adjuvant/neoadjuvant setting is allowed, but patients must have been off such therapy for greater than or equal to 1 week prior to registration
- •No prior radiotherapy other than to the conserved breast, to the postmastectomy chest wall or to a limited field involving less than 25% of marrow - containing bone
- •Previously irradiated tumors cannot be used to assess a clinical response; patients will not be eligible for this study if the previously irradiated tumors constitute the only site of measurable disease
- •Patients must not have previously received tipifarnib or other farnesyl transferase inhibitors
- •Patients must be disease-free of prior malignancies for \> 5 years with the exception of curatively treated basal or squamous cell carcinomas of the skin or carcinoma in situ of the cervix
- •Patients must have serum creatinine =\< 1.5 mg/dl or measured (or calculated) creatinine clearance \>= 60 mL/minute
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (tipifarnib, capecitabine)
Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 4 additional courses beyond documentation of CR.
Intervention: tipifarnib
Treatment (tipifarnib, capecitabine)
Patients receive oral tipifarnib twice daily and oral capecitabine twice daily on days 1-14. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) receive 4 additional courses beyond documentation of CR.
Intervention: capecitabine
Outcomes
Primary Outcomes
Objective response rate (PR+CR)
Time Frame: Up to 5 years
Secondary Outcomes
- Progression-free survival (PFS)(From registration to progression or to death from any cause without documentation of progression, assessed up to 5 years)
- Time to treatment failure (TTF)(From registration to disease progression, permanent discontinuation of treatment due to toxicity, or death, whichever occurs first, assessed up to 5 years)
- Overall survival (OS)(Up to 5 years)
- Incidence of toxicities(Up to 5 years)