Patient case: 45-year-old female with cervical cancer; genetic feature: ERBB2 (S310Y)

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

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: 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.

Relevance to patient case: not relevant