GW572016 For Treatment Of Refractory Metastatic Breast Cancer

An Open-Label, Multicenter, Single Arm Phase II Study of Oral GW572016 as Single Agent Therapy in Subjects With Advanced or Metastatic Breast Cancer Who Have Progressed While Receiving HERCEPTIN-Containing Regimens

This study was designed to determine the efficacy of an oral dual kinase inhibitor for the treatment of metastatic breast cancer tumors that are known to overexpress ErbB2 in a refractory patient population.

Inclusion Criteria:

• Signed Informed Consent.
• Histologically confirmed Stage IIIb or IV breast cancer.
• Refractory breast cancer defined as progression in the metastatic setting after prior therapy with anthracyclines, taxanes and capecitibine.
• Subjects with documented ErbB2 tumor overexpression must have received at least 6 cycles of trastuzumab.
• Documented disease progression of the most recent treatment is required.
• Archived tumor tissue available for testing.
• Measurable lesions according to Response Evaluation Criteria In Solid Tumors (RECIST).
• At least 3 weeks since prior cancer therapies except for trastuzumab which must be discontinued at least 2 weeks prior to the beginning of study drug.
• Bisphosphonate therapy initiated prior to study entry is allowed, however, initiation of bisphosphonates following study entry is not allowed.
• Able to swallow and retain oral medication.
• Cardiac ejection fraction within the institutional normal range as measured by echocardiogram or MUGA (Multiple Gated Acquisition) scan.
• Adequate kidney and liver function.
• Adequate bone marrow function.

Exclusion criteria:

• Pregnant or lactating.
• Copies of nadir scans and/or photographs of the tumor prior to disease progression as well as scans documenting disease progression are not available for review.
• Malabsorption syndrome, ulcerative colitis, disease significantly affecting gastrointestinal function or resection of the stomach or small bowel.
• History of other malignancy.
• Serious medical or psychiatric disorder that would interfere with the patient''s safety or informed consent.
• Active or uncontrolled infection.
• Known history of uncontrolled or symptomatic angina, arrhythmias or congestive heart failure.
• Known history of or clinical evidence of leptomeningeal carcinomatosis.
• Active infection.
• Concurrent cancer therapy or investigational therapy.
• Use of oral or IV steroids.
• Unresolved or unstable serious toxicity from prior therapy.
• Prior treatment with an ErbB1 and/or ERbB2 inhibitor other than trastuzumab.