A Study to Examine the Effects of Low and High-fat Meals on Orally Administered Lapatinib in Metastatic ErbB2 Positive Breast Cancer Patients

An Open Label Study to Examine the Effects of Low-Fat and High-Fat Meals on the Pharmacokinetics of Orally Administered Lapatinib in Metastatic ErbB2 Positive Breast Cancer Patients

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.

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.