a study to examine the effects of esomeprazole on the pharmacokinetics of orally administered lapatinib in subjects with metastatic erbb2 positive breast cancer

Conditions: Neoplasms, Breast

Summary: this study will characterize the effect of elevated gastric ph mediated by the proton-pump inhibitor, esomeprazole, on the relative bioavailability of lapatinib in subjects with metastatic erbb2 positive breast cancer.


Eligibility criteria:
inclusion criteria: * metastatic, histologically confirmed breast cancer that overexpresses erbb2 (3+ by ihc, fish, or cish positive). * 18 years to 65 years of age. * is male or female (of non childbearing potential or willing to use contraception as specified in the protocol). * is able to swallow and retain oral medication. * ecog performance status 0 to 2. * provided written informed consent. * adequate bone marrow function (as specified in the protocol). * calculated creatinine clearance (crcl) greater than or equal to 50 ml/min based on cockcroft and gault. * total bilirubin less than or equal to 1.5 x upper limit of normal of institutional values. * alanine transaminase (alt) less than or equal to 3 times the upper limit of the institutional values or less than or equal to 5 times uln with documented liver metastases * has a left ventricular ejection fraction (lvef) within the normal institutional range based on echo or muga. * life expectancy of greater than or equal to 12 weeks * capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. exclusion criteria: * pregnant or lactating woman. * has malabsorption syndrome, a disease affecting gastrointestinal function, or resection of the stomach or small bowel. * has current active hepatic or biliary disease (with exception of patients with gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) * has evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease. subjects with brain metastases treated by surgery and/or radiotherapy are eligible if neurologically stable and do not require steroids or anticonvulsants. * is considered medically unfit for the study by the investigator. * has a known immediate or delayed benzimidazole hypersensitivity reaction or idiosyncrasy to drugs chemically related to the investigational product such as gefitinib \[iressa\] and erlotinib \[tarceva\]. * has received treatment with any investigational drug in the previous four weeks. (with the exception of lapatinib). * has received chemotherapy, immunotherapy, biologic therapy or hormonal therapy for the treatment of cancer within the past 14 days, with the exception of mitomycin c which is restricted for the past six weeks, and lapatinib. subjects receiving lapatinib prior to study entry are eligible to participate in the study. * is receiving any prohibited medication within the timeframe indicated on the prohibited medication list in the protocol. * has physiological, familial, sociological, or geographical conditions that do not permit compliance with the protocol. * has inadequate venous access for protocol-related blood draws. * clinically significant electrocardiogram abnormality. * history of sensitivity to heparin or heparin-induced thrombocytopenia. * consumption of red wine, seville oranges, grapefruit or grapefruit juice and/or kumquats, pummelos, exotic citrus fruit (i.e. star fruit, bitter melon), grapefruit hybrids or fruit juices from seven days prior to the first dose of study medication.

Keywords: lapatinib (gw572016), subject, pharmacokinetic, esomeprazole, proton-pump inhibitor, drug interaction, phase 1