This phase II trial is studying how well giving tipifarnib together with fulvestrant works as second-line therapy in treating postmenopausal women with hormone receptor-positive inoperable locally advanced or metastatic breast cancer that has progressed after previous first-line endocrine therapy. Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by blocking the use of estrogen. Combining tipifarnib with fulvestrant may kill tumor cells that did not respond to first-line therapy.
PRIMARY OBJECTIVES: I. To determine the efficacy of tipifarnib (R115777, Zarnestra™) in combination with fulvestrant based on clinical benefit rate (CBR, a combination of complete response rate, partial response rate, and stable disease for more than 24 weeks) in postmenopausal women with hormone receptor-positive metastatic breast cancer who have progressive disease after first-line endocrine therapy. SECONDARY OBJECTIVES: I. To determine the median time to progression (TTP) and duration of response of tipifarnib (R115777, Zarnestra™) in combination with fulvestrant in postmenopausal women with hormone receptor-positive metastatic breast cancer. II. To determine the median overall survival of tipifarnib (R115777, Zarnestra™) in combination with fulvestrant in postmenopausal women with hormone receptor- positive metastatic breast cancer who have progressive disease after first-line endocrine therapy. III. To determine the toxicity profile of tipifarnib (R115777, Zarnestra™) in combination with fulvestrant versus fulvestrant alone (from historical control) in postmenopausal women with hormone receptor positive metastatic breast cancer who have progressive disease after first-line endocrine therapy. OUTLINE: Patients receive fulvestrant intramuscularly on day 1 and oral tipifarnib twice daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity\*. NOTE: \*Fulvestrant continues even if tipifarnib is held for toxicity. Patients are followed every 3 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Given intramuscularly
Given IV
Montefiore Medical Center
The Bronx, New York, United States
Clinical Benefit Rate (CBR) (CR Rate, PR Rate, and SD)
Number of participants met the definition of Clinical Benefit Rate.Tumor response was assessed every three cycles by CT using RECIST (Response Evaluation Criteria In Solid Tumors) criteria. Per Response Evaluation Criteria in Solid Tumors (RECIST 1.0) for target lesions: Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time frame: Up to 24 weeks
Time to Progression (TTP)
TTP was estimated using the Kaplan-Meier method.
Time frame: From randomization until progression of the disease, assessed up to 4 years
Duration of Response
DOR was defined for responders as the time from the onset of first response to disease progression and for non-responders as zero
Time frame: Up to 4 years
Toxicity as Assessed by NCI CTCAE Version 3.0
Number of Participants with serious (grade 3) or life-threatening (grade 4) adverse events
Time frame: Up to 4 years
Median Overall Survival
The 95% confidence intervals will be used.
Time frame: From randomization until death or censored at the date of last follow-up, assessed up to 4 years
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