A Study to Evaluate the Antitumor Activity and Safety of IPI-504 in Patients With Advanced Breast Cancer

Inclusion Criteria

• •Adult women at least 18 years of age at the time of signing the Informed Consent Form;
• •Written informed consent and HIPAA authorization (applies to covered entities in the USA only) obtained from the patient prior to performing any study-related procedures, including screening visits;
• •Pathologically confirmed breast cancer from assessment of primary or metastatic breast cancer;
• •Locally advanced or metastatic breast cancer as defined as a T4 primary tumor and Stage IIIB/ IIIC disease or Stage IV disease, respectively, according to the Sixth Edition of the American Joint Committee on Cancer \[AJCC\] TNM System (Appendix A);
• •Measurable disease according to RECIST - lesions that can be accurately measured in at least one dimension with longest diameter ³ 20 mm using conventional computed tomography (CT) or magnetic resonance imaging (MRI) scan or ³ 10 mm with spiral CT scan; the use of chest x-ray is not encouraged, however, it may be used if necessary;
• •HER2-expressing primary or metastatic tumor (Grade 3+ staining intensity \[on a scale of 0 to 3\] via IHC assays or HER2 amplification on fluorescence in situ hybridization), with results of the most recent biopsy taken as indicative of HER2 status;
• •Progression after treatment with at least 1 but not more than 3 regimens containing trastuzumab or lapatinib (treatment regimens that do not include trastuzumab or lapatinib do not qualify) for adjuvant, neoadjuvant, locally advanced, or metastatic disease with either one of the following stipulations:
• •1. Patients may have received neoadjuvant or adjuvant treatment with prior trastuzumab or lapatinib treatment but must have demonstrated no evidence of disease progression for \>12 months following completion of therapy;
• •2. Patients have received a trastuzumab-based therapy for locally advanced or metastatic disease for a minimum of 9 weeks duration. Patients may have received more than 1 trastuzumab-based combination therapy; Patients have received a lapatinib-based therapy for locally advanced or metastatic diseases for a minimum of 9 weeks duration;
• •Resolution of all toxic side effects of prior chemotherapy, radiotherapy or surgical procedures to NCI CTCAE Grade ≤ 1 or patient's baseline;
• •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (see Appendix B);
• •Life expectancy of at least 3 months;
• •Left ventricular ejection fraction \> 45%;
• •Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3; platelet count ≥ 100,000 cells/mm3; hemoglobin ≥ 9.0 g/dL (may be increased to this level with transfusion as long as there is no evidence of active bleeding);
• •Prothrombin time or international normalized ratio within normal range (unless a patient is receiving anticoagulation therapy), or PTT within normal range;
• •AST and ALT ≤ 2.5 ´ upper limit of normal (ULN) or ≤ 5 ´ ULN for patients with liver metastases; total bilirubin ≤ 1.5 ´ ULN \[unless due to Gilbert's syndrome (unconjugated hyperbilirubinemia) in which case the bilirubin should be \< 3.5mg/dL); hepatic alkaline phosphatase ≤ 2.5 ´ ULN;
• •Serum creatinine ≤ 1.5 ´ ULN and calculated creatinine clearance ≥ 30 mL/min;
• •Female patients must be of non child-bearing potential or using effective contraception, eg, use of oral contraceptives with an additional barrier method (since the study drug may impair the effectiveness of oral contraceptives), double barrier methods (diaphragm with spermicidal gel or condoms with contraceptive foam), Depo-Provera, partner vasectomy, total abstinence, and willing to continue the effective contraception method for 30 days after the last dose of IPI-504; and
• •Patients must be able to adhere to the study visit schedule and all protocol requirements.