a study to examine the effects of low and high-fat meals on orally administered lapatinib in metastatic erbb2 positive breast cancer patients

Conditions: Neoplasms, Breast

Summary: this study will be a randomized 3-treatment, cross-over study to evaluate the bioavailability of lapatinib administered after a high or low-fat meal.


Eligibility criteria:
inclusion criteria: * metastatic, histologically confirmed breast cancer that over-expresses erbb2 (3+ by ihc; fish or cish positive). * is at least 18 years of age and not greater than 65 years of age. * is male or female. a female is eligible to enter and participate in the study if she is of: 1. non-childbearing potential (i.e. physiologically incapable of becoming pregnant), including any female who: has had a hysterectomy; has had a bilateral oophorectomy (ovariectomy); has had a bilateral tubal ligation, or is post-menopausal (a demonstration of total cessation of menses for ≥ 1 year) or in questionable cases a blood sample with simultaneous follicle stimulating hormone (fsh) \> 40 mlu/ml and estradiol \< 40 pg/ml (\<140 pmol/l) is confirmatory. 2. childbearing potential, has a negative serum pregnancy test at screening and agrees to one of the following: double-barrier contraception (condom with spermicidal jelly, foam, suppository, or film; diaphragm with spermicide; or male condom and diaphragm); complete abstinence from sexual intercourse from two weeks prior to administration of the study drug, throughout the active study treatment period; vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female. * is able to swallow and retain oral medication. * ecog performance status 0 to 2. * adequate bone marrow function. * hemoglobin ≥ 9 gm/dl. * absolute granulocyte count ≥1,500/mm3 (1.5 x 109/l). * platelets ≥ 75,000/mm3 (75 x 109/l). * calculated creatinine clearance (crcl) ≥ 50 ml/min based on cockcroft and gault * total bilirubin ≤ 1.5 x upper limit of normal of institutional values and inr ≤ 1.5. * alanine transaminase (alt) ≤ three times the upper limit of the institutional values or ≤ five 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 ≥12 weeks * capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. exclusion criteria: * is pregnant or lactating. * 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 as a result of the medical interview, physical exam, or screening investigations. * has a known immediate or delayed 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. * 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. * is receiving any prohibited medication within the timeframe indicated on the prohibited medication list for this study. * 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 (ecg) abnormality. * history of sensitivity to heparin or heparin-induced thrombocytopenia. * has consumed 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 7 days prior to the first dose of study medication.

Keywords: phase i food effect