Neoplasms, Breast
Conditions
Keywords
Phase I Food Effect
Brief 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.
Interventions
DRUGLapatinib
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.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Protocol specified pharmacokinetic parameters | 3 weeks |
Secondary
| Measure | Time frame |
|---|---|
| Safety and tolerability as assessed by evaluation of adverse events (AEs), changes in laboratory values, and vital signs | 3 weeks |
Countries
Canada, Netherlands, United States
Outcome results
None listed