APRiCOT-B: Study to Evaluate Apricoxib in Combination With Lapatinib and Capecitabine in the Treatment of HER2/Neu+ Breast Cancer (TP2001-202)

A Phase 2 Study of the Efficacy and Safety of Apricoxib in Combination With Lapatinib and Capecitabine in the Treatment of Patients With HER2/Neu+ Breast Cancer Who Have Failed Trastuzumab and Chemotherapy Including a Taxane

This study will compare the anti-tumor efficacy of apricoxib and lapatinib/capecitabine with placebo and lapatinib/capecitabine as measured by time to disease progression and evaluate urinary PGE-M measurements or baseline COX-2 expression in tumor tissue by IHC as a surrogate selection criterion for patients who will benefit from future treatment with apricoxib.

Inclusion Criteria:

• Females with pathologically determined locally advanced or metastatic human epidermal growth factor receptor 2 positive (HER2/neu+) breast cancer
• Have progressed after treatment with chemotherapy including a taxane and trastuzumab
• Must have measurable disease by RECIST
• ECOG PS of 0,1, or 2
• MUGA scan or echocardiogram results show left ventricular ejection fraction greater than or equal to 50%

Exclusion Criteria:

• Radiation therapy within 2 weeks, chemotherapy within 3 weeks, or noncytoxic investigational agents within 4 weeks of initiating study treatment
• Evidence of New York Heart Association class III or greater cardiac disease
• History of MI, stroke, ventricular arrhythmia, or symptomatic conduction abnormality
• History of congenital QT prolongation
• Concurrent severe or uncontrolled medical disease
• Symptomatic central nervous system metastases
• Pregnant or nursing women
• Hypersensitivity or intolerance to apricoxib, lapatinib, capecitabine, 5-FU, sulfonamides, aspirin, or NSAIDs
• Severe renal insufficiency
• History of upper GI bleeding, ulceration, or perforation- Concurrent use of potent CYP3A4 inhibitors and CYP3A4 inducers
• Prior treatment with capecitabine
• Patients on anti-arrhythmic treatment
• Prior lapatinib therapy