Brain Metastases In ErbB2-Positive Breast Cancer

Inclusion Criteria

• •Subjects eligible for enrollment in the study must meet all of the following criteria:
• •Signed written informed consent;
• •Females or males age ≥ 18 years old;
• •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1;
• •Life expectancy of at least 12 weeks;
• •Subjects must have histologically or cytologically confirmed invasive breast cancer, with Stage IV disease;
• •ErbB2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with ErbB 2 gene amplification by FISH, or ErbB 2 gene amplification by FISH alone (in subjects whose tumor blocks were not assessed by IHC). Subjects with tumors that are 2+ by IHC but negative or borderline by FISH assay are ineligible. For subjects with a history of more than one primary breast cancer, each breast cancer must be ErbB2 overexpressing to be eligible;
• •ErbB2 overexpressing breast cancer, defined as 3+ staining by immunohistochemistry (IHC), or 2+ staining by IHC in conjunction with ErbB2 gene amplification by FISH, or ErbB2 gene amplification by FISH alone (in subjects whose tumor blocks were not assessed by IHC). ErbB2 gene amplification is defined by: \> 6 ErbB2 gene copies/nucleus for test systems without an internal control probe or an ErbB2/CEP 17 ratio of more than 2.2. Subjects with tumors that are 2+ by IHC but negative or borderline by FISH assay are ineligible. For subjects with a history of more than one primary breast cancer, each breast cancer must be ErbB2 overexpressing to be eligible;
• •Prior treatment of brain metastases with WBRT and/or SRS;
• •Unequivocal evidence of new and / or progressive lesions in the brain on an imaging study; Note: Subjects with progressive brain lesions are not required to meet RECIST criteria for CNS progression in order to be eligible for this study.
• •Prior treatment with trastuzumab, either alone or in combination with chemotherapy is required. Trastuzumab will be discontinued at least 2 weeks prior to enrollment on study;
• •Cardiac ejection fraction within institutional range of normal as measured by echocardiogram. Subjects who require cardiac medications (e.g. positive inotropic agents or afterload reducers) for normal ejection fraction are ineligible. MUGA scans will be accepted in cases where an echocardiogram cannot be performed or is inconclusive;
• •At least 2 weeks since prior radiotherapy, last chemotherapy, immunotherapy, biologic therapy, or hormonal therapy for cancer, and sufficiently recovered or stabilized from side effects associated with prior therapy. Concurrent treatment with bisphosphonates is permitted;
• •At least 3 weeks since major surgical procedures;
• •Able to swallow and retain oral medications;
• •Women of childbearing potential must have a negative serum pregnancy test at screening and must use an approved contraceptive method, if appropriate (for example, intrauterine device \[IUD\], birth control pills, or barrier device) beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product. Males able to father a child must practice adequate methods of birth control or practice complete abstinence from intercourse from the first dose of investigational treatment until one week after the final dose of investigational treatment.
• •Subjects must complete all screening assessments as outlined in the protocol;
• •Normal organ and marrow function as defined by these LABORATORY VALUES : ANC (absolute neutrophil count) ≥ 1.5 x 10\^9/L; Hemoglobin ≥ 10 g/dL (after transfusion if needed); Platelets ≥ 100 x 10\^9/L; Albumin ≥ 2.5 g/dL; Serum bilirubin ≤ 1.5x ULN unless due to Gilbert's syndrome; AST and ALT ≤ 5x ULN if documented liver metastases ≤ 3x ULN without liver metastases; Serum Creatinine ≤ 1.2 mg/dL or Calculated Creatinine Clearance1 ≥ 50 mL/min