A Phase 1/2 Study Of HKI-272 (Neratinib) in Combination With Trastuzumab (Herceptin) In Subjects With Advanced Breast Cancer

Inclusion Criteria

• Pathologic diagnosis of breast cancer with current stage IIIB, IIIC or IV not curable by available therapy
• Progression following at least one Herceptin-containing cytotoxic chemotherapy regimen (neoadjuvant, adjuvant, or metastatic setting)
• HER2 positive breast cancer
• At least one measurable target lesion
• Adequate performance status
• Adequate cardiac, kidney, and liver function
• Adequate blood counts
• Willingness of all subjects who are not surgically sterile or post menopausal to use acceptable methods of birth control

Exclusion Criteria

• More than 3 prior cytotoxic chemotherapy regimens for locally advanced or metastatic disease
• Major surgery, chemotherapy, radiotherapy, investigational agents, Herceptin or other cancer therapy within 2 weeks of treatment day 1
• Prior treatment with anthracyclines with cumulative dose of >400 mg/m^2
• Extensive visceral disease
• Active central nervous system metastases
• Pregnant or breast feeding women
• Significant chronic or recent acute gastrointestinal disorder with diarrhea as a major symptom
• Prior exposure to HKI-272 or other HER2 targeted agents (except Herceptin and Tykerb)
• Significant cardiac disease or dysfunction
• History of life-threatening hypersensitivity to Herceptin
• Inability or unwillingness to swallow HKI-272 capsules
• Any other cancer within 5 years with the exception of contralateral breast cancer, adequately treated cervical carcinoma in situ, or adequately treated basal or squamous cell carcinoma of the skin