An Open-Label, Single Sequence Study to Examine the Effects of Esomeprazole on the Pharmacokinetics of Orally Administered Lapatinib in Subjects With Metastatic ErbB2 Positive Breast Cancer
- 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
- 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
- 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.
- 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.