Tipifarnib and Fulvestrant in Hormone Receptor-Positive Metastatic Breast Cancer

Inclusion Criteria

• Patients must have histologically or cytologically confirmed adenocarcinoma of the breast
• Patients must be postmenopausal
• Patients must have stage IV disease or inoperable locally advanced disease
• Patients must have ER- and/or PR-positive disease as determined by their local pathology laboratory
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan; all sites of disease should be noted and followed
• Prior hormonal therapy as adjuvant therapy and/or for metastatic disease is permitted; patients previously treated with two or more prior doses of fulvestrant are not eligible; patients who have received one prior dose of fulvestrant within 28 days are eligible so long as they meet other eligibility criteria
• Patients must have ECOG performance status 0-2 (Karnofsky >= 60%)
• Patients must have life expectancy of greater than 3 months
• Leukocytes >= 3,000/uL
• Absolute neutrophil count >= 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin = = 5 years with the exception of: curatively-treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix
• Patients must have the ability to understand and the willingness to sign a written informed consent document
• Patients who have had previous therapy with farnesyltransferase inhibitor

Exclusion Criteria

• Patients who have had radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; patients who have had prior chemotherapy for metastatic disease are not eligible; prior adjuvant or neoadjuvant chemotherapy is allowed
• Patients may not be receiving any other investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to tipifarnib (R115777, Zarnestra™) or other agents used in the study (e.g., imidazoles, quinolones)
• Presence of rapidly progressive, life-threatening metastases; this includes patients with extensive hepatic involvement (> 50% of the liver involved), symptomatic lymphangitic metastases, or brain or leptomeningeal involvement
• Concomitant anticancer treatment with the following exceptions: (1) bisphosphonates for bone metastases, (2) a GnRH analog is permitted if the patient had progressive disease on a GnRH analog plus a SERM or an AI; the GnRH analog may continue but the SERM or AI must be discontinued
• Grade 2 or more peripheral neuropathy
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with tipifarnib or other agents administered during the study.; appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated