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A Four-Way Cross-Over Study to Examine the Effects of Lapatinib on the Pharmacokinetics of Orally and Intravenously Administered Midazolam in Cancer Patients

Phase 1
18 Years
70 Years
Not Enrolling

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Trial Information

A Four-Way Cross-Over Study to Examine the Effects of Lapatinib on the Pharmacokinetics of Orally and Intravenously Administered Midazolam in Cancer Patients

Inclusion 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Principal Investigator

GSK Clinical Trials, MD

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

November 2005

Completion Date:

Related Keywords:

  • Cancer
  • lapatinib
  • midazolam
  • pharmacokinetics



GSK Investigational Site Raleigh, North Carolina  27609
GSK Investigational Site Hooksett, New Hampshire  03106