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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Neoplasms, Breast

Intervention / Treatment
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* Drug: Lapatinib


Participation Criteria
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Eligibility Criteria
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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: 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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1<br>Treatment A, B or C | Drug: Lapatinib<br>* Treatment A: one dose of 1250mg lapatinib 1 hour before starting a low-fat breakfast; Treatment B: one dose of 1250mg lapatinib 1 hour after finishing a low fat breakfast; or Treatment C: one dose of 1250mg lapatinib 1 hour after finishing a high-fat breakfast.<br>* Other names: TYKERB - US; TYVERB - UK;|
| Experimental: Period 2<br>Treatment A, B or C | Drug: Lapatinib<br>* Treatment A: one dose of 1250mg lapatinib 1 hour before starting a low-fat breakfast; Treatment B: one dose of 1250mg lapatinib 1 hour after finishing a low fat breakfast; or Treatment C: one dose of 1250mg lapatinib 1 hour after finishing a high-fat breakfast.<br>* Other names: TYKERB - US; TYVERB - UK;|
| Experimental: Period 3<br>Treatment A, B or C | Drug: Lapatinib<br>* Treatment A: one dose of 1250mg lapatinib 1 hour before starting a low-fat breakfast; Treatment B: one dose of 1250mg lapatinib 1 hour after finishing a low fat breakfast; or Treatment C: one dose of 1250mg lapatinib 1 hour after finishing a high-fat breakfast.<br>* Other names: TYKERB - US; TYVERB - UK;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Protocol specified pharmacokinetic parameters |  | 3 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability as assessed by evaluation of adverse events (AEs), changes in laboratory values, and vital signs |  | 3 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase I Food Effect