To Examine The Effects Of Lapatinib On Orally And Intravenously Administered Midazolam In Cancer Patients

• Status: Completed
• Trial end date: 2007-02-08
• Target enrollment: 0
• Participant gender: All

Summary

To characterize the effect of repeat oral dose of lapatinib treatment on the pharmacokinetics of a single oral and single intravenous dose of midazolam in adult cancer patients. Also to assess the safety and tolerability of chronic oral lapatinib therapy in cancer patients.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Lapatinib; Midazolam

Criteria

Inclusion criteria:

• 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 institutional values.

• 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%.

Exclusion criteria:

• 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 may exist).

• 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 screening.

• 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 is administered.

• 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 draws.