A Phase 2 Multicenter Study Evaluating the Efficacy and Safety of IPI-504 in Combination With Trastuzumab in Patients With Pretreated, Locally Advanced or Metastatic Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer

Study start date: March 1, 2009

Inclusion Criteria: * Locally advanced/metastatic breast cancer. * HER2-expressing primary or metastatic tumor * Two prior regimens with HER2. Trastuzumab must have been given. No limit to prior therapies * Measurable disease with RECIST 1.1 * Clinical progression * LVEF WNL * ECOG 0 or 1 * Last dose of chemotherapy, radiotherapy, surgery, ablative therapy, tyrosine kinase inhibitor, ≥2 weeks * Administration of biological therapy ≥4 weeks * Last dose of trastuzumab must be ≥1, or ≥3 weeks prior to start, if previously administered on an every 3 week schedule. * Resolution of toxic effects to baseline or Grade 1, except alopecia (NCI CTCAE Version 3.0 * Organ and marrow function: * Hemoglobin ≥8.0 g/dL * ANC ≥1200/µL * Platelets ≥75,000 /µL * ALT and AST ≤ 1.5 x ULN * Alkaline phosphatase ≤2.5 x ULN, or ≤3.0 x ULN if secondary to liver metastases. * Serum bilirubin WNL * Serum albumin ≥3.0 g/dL * PT, PTT ≤1.5 x ULN * Serum creatinine ≤1.5 x ULN * Negative pregnancy test Exclusion Criteria: * Prior treatment with Hsp90 inhibitor. * Grade 4 AE secondary to trastuzumab. Grade 3/4 infusion reactions or Grade 3/4 symptomatic heart failure * Medication/food that is a CYP3A inhibitor or inducer. * Hx 6 months: cardiac disease - acute coronary syndrome or unstable angina, symptomatic congestive heart failure, uncontrolled hypertension, cirrhotic liver disease, cerebrovascular accident or significant co-morbid condition * Grade 3 or 4 hemorrhagic event within 6 months. * HIV positivity * Baseline QT corrected, QTcF \>470 ms * Sinus bradycardia \<50 bpm Secondary to pharmacologic therapy may enroll if stopping therapy normalizes heart rate. * Malignancies within 3 years other than non-melanomatous skin cancers, non-muscle-invasive bladder cancer and carcinoma in situ of cervix. * Active keratitis or keratoconjunctivitis * Active brain metastasis (e.g., requiring therapy with steroids or radiation therapy; or with intracranial progression 4 weeks after the completion of radiation therapy) uncontrolled seizure disorder, ongoing spinal cord compression, or carcinomatous meningitis. If clinically stable brain metastasis (previously treated or untreated)are present pt is eligible.