Tipifarnib and Fulvestrant in Hormone Receptor-Positive Metastatic Breast Cancer
Condition: Estrogen Receptor-positive Breast Cancer; Recurrent Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: fulvestrant; tipifarnib
Intervention description: Given intramuscularly; Given IV
Intervention MeSH terms: Fulvestrant; Tipifarnib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 33.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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, 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