RATIONALE: Lapatinib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: This phase I/II trial is studying the side effects and best dose of lapatinib and to see how well it works in treating patients with recurrent glioblastoma multiforme.
OBJECTIVES: Phase I * Determine the maximum tolerated dose and recommended phase II dose of lapatinib in patients with recurrent malignant glioblastoma multiforme who are taking CYP3A4 enzyme-inducing anti-epileptic drugs (EIAEDs). * Determine the toxic effects of this drug in these patients. * Determine the pharmacokinetics of this drug in these patients. Phase II * Determine the efficacy of this drug, in terms of objective tumor response rate, in patients who are taking EIAEDs and in those who are not taking EIAEDs. * Correlate immunohistochemical measures of cellular proteins and receptors from tumor samples with anti-tumor activity of this drug in these patients. * Determine the pharmacokinetics of this drug in these patients. OUTLINE: This is a multicenter, open-label, phase I, dose-escalation study followed by a phase II study. * Phase I: Patients receive oral lapatinib twice daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of lapatinib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. * Phase II: Patients receive lapatinib as in phase I at the MTD. Patients are followed at 1 month and then periodically for survival. Patients with stable or responding disease who go off therapy are followed every 3 months for up to one year and then periodically thereafter for survival. PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for the phase I portion of this study within 18 months. A total of 15-30 patients will be accrued for the phase II portion of this study within 18 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
For patients receiving enzyme inducing anti-epileptic drugs (EIAEDs): * Phase I: starting dose for first cohort: 1000 mg GW572016 po b.i.d.; actual dose assigned at registration; intra patient dose escalation permitted ONCE in phase I patients ONLY if specified criteria met (see section 8.6). * Phase II: Recommended phase II dose from phase I portion of the study, given po b.i.d. For patients NOT receiving enzyme inducing anti-epileptic drugs (NON-EIAEDs): • Phase II: 750 mg GW572016 po b.i.d. For all patients: • Dose reductions as required based on adverse events.
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada
British Columbia Cancer Agency - Centre for the Southern Interior
Kelowna, British Columbia, Canada
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada
Toxicity for phase I assessed by CTCAE v.3.0 MacDonald criteria
Time frame: 7 years
Response for phase II
Time frame: 7 years
Correlative studies on archival tissue
Time frame: 7 years
Pharmacokinetics
Time frame: 7 years
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Princess Margaret Hospital
Toronto, Ontario, Canada
Centre Hospitalier de l'Universite de Montreal
Montreal, Quebec, Canada