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