A Four-Way Cross-Over Study to Examine the Effects of Lapatinib on the Pharmacokinetics of Orally and Intravenously Administered Midazolam in Cancer Patients
- Histologically confirmed, solid tumor refractory to standard therapy.
- Tumor for which there is no standard therapy.
- Able to swallow and retain oral medication.
- ECOG (Eastern Cooperative Oncology Group) performance status 0 to 2.
- Provided written informed consent.
- Adequate bone marrow function.
- Serum creatinine is less than or equal to 1.5 mg/dL.
- Calculated creatinine clearance is greater than or equal to 60 ml/min based on
Cockcroft and Gault.
- Total bilirubin is greater than or equal to the upper limit of normal of
- Aspartate and alanine transaminase is less than or equal to 3 times the upper limit
of the institutional values.
- Have a left ventricular ejection fraction (LVEF) greater than or equal to 40% based
on electrocardiogram (ECHO) or multiple gated acquisition scan (MUGA).
- Resting oxygen saturations of greater than 90%.
- Pregnant or lactating female.
- Have malabsorption syndrome, a disease affecting gastrointestinal function.
- Resection of the stomach or small bowel.
- Evidence of symptomatic or uncontrolled brain metastases or leptomeningeal disease.
- Is considered medically unfit for the study by the investigator as a result of the
medical interview, physical exam, or screening investigations.
- Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the investigational product.
- Use of anilinoquinazolines, such as gefitinib [Iressa™], erlotinib [Tarceva™].
- Immediate or delayed hypersensitivity reaction to midazolam or any component of the
formulation, including benzyl alcohol (cross-sensitivity with other benzodiazepines
- Has narrow-angle glaucoma which is a contraindication to midazolam use.
- Has received treatment with any investigational drug in the previous 4 weeks.
- Received chemotherapy, immunotherapy, biologic therapy or hormonal therapy within the
past 14 days, with the exception of mitomycin C within the past 6 weeks.
- Currently receiving amiodarone or has received amiodarone in the 6 months prior to
- Is taking regular doses of opiates that in the opinion of the investigator would put
the patient at risk of clinically significant respiratory compromise when midazolam
- Physiological, familial, sociological, or geographical conditions that do not permit
compliance with the protocol.
- Has Class II to IV heart failure as defined by the New York Heart Association (NYHA)
functional classification system.
- Clinically significant electrocardiogram (ECG) abnormality.
- Clinically assessed to have inadequate venous access for protocol-related blood