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 =< 2 mg/dL
AST(SGOT)/ALT(SGPT) =< 2.5 x institutional upper limit of normal
Creatinine less than or equal to 1.5 times the institutional upper limits of normal
Patients must be disease-free of prior invasive malignancies for >= 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, Zarnestraâ„¢) 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