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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Neoplasms, Breast

Treatments: Drug: Midazolam; Drug: Lapatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT00258050

EGF10015

Details and patient eligibility

About

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.

Enrollment: 24 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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24 participants in 1 patient group

Subjects with cancer

Experimental group

Description:

In Part 1 of the study, subjects will be randomized to one of four sequences. All subjects will receive oral or intravenous (IV) midazolam on Days 1, 3, 9 and 11 as per assigned randomization scheme. Starting on Day 4 through Day 11, subjects will receive a daily dose of 1500 milligrams (mg) of oral lapatinib. In Part 2, which will begin on Day 12, the subjects will be required to take 1500 mg of lapatinib daily until removed from the study for disease progression, adverse events, withdrawal of consent, or transfer to another lapatinib study.

Treatment:

Drug: Lapatinib

Drug: Midazolam