Clinical Trial Finder

DISEASE CHARACTERISTICS:

• - Histologically confirmed malignant glioblastoma multiforme.

• - Recurrent or progressive disease after prior primary treatment with radiotherapy with or without adjuvant chemotherapy.

• - Bidimensionally measurable disease on CT scan or MRI with at least one lesion ≥ 1 cm x 1 cm.

• - Paraffin embedded tumor sample available.

• - Concurrent enzyme-inducing anti-epileptic drugs (EIAEDs) required for phase I of the study.

• - Patients in phase II of the study may or may not be receiving EIAEDs.

PATIENT CHARACTERISTICS: Age.

• - 18 and over.

Performance status.

• - ECOG 0-2.

Life expectancy.

• - Not specified.

Hematopoietic.

• - Absolute granulocyte count ≥ 1,500/mm^3.

• - Platelet count ≥ 100,000/mm^3.

Hepatic.

• - Bilirubin ≤ upper limit of normal (ULN) - AST and ALT ≤ 2.5 times ULN.

Renal.

• - Creatinine ≤ 1.5 times ULN.

Cardiovascular.

• - LVEF ≥ 50% by echocardiogram or MUGA.

• - No myocardial infarction within the past 6 months.

• - No congestive heart failure.

• - No unstable angina.

• - No active cardiomyopathy.

• - No cardiac arrhythmia.

• - No uncontrolled hypertension.

Pulmonary.

• - No pulmonary disease requiring oxygen.

Neurologic.

• - No preexisting peripheral neuropathy ≥ grade 3.

• - No history of significant neurologic disorder that would preclude study compliance or ability to give informed consent.

Gastrointestinal.

• - No upper gastrointestinal or other conditions that would preclude compliance with oral medication.

• - No active peptic ulcer disease.

Other.

• - No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively treated solid tumor.

• - No immune deficiency.

• - No history of significant psychiatric disorder (e.g., uncontrolled psychotic disorders) that would preclude study compliance or ability to give informed consent.

• - No other serious illness or medical condition that would preclude study participation.

• - No known hypersensitivity to compounds of similar chemical or biological composition to lapatinib.

• - No active uncontrolled or serious infection.

• - HIV negative.

• - Not pregnant or nursing.

• - Negative pregnancy test.

• - Fertile patients must use effective contraception.

PRIOR CONCURRENT THERAPY: Biologic therapy.

• - No concurrent prophylactic filgrastim (G-CSF), sargramostim (GM-CSF), or other hematopoietic growth factors.

• - Concurrent hematopoietic growth factors allowed for treatment of acute toxicity (e.g., febrile neutropenia) Chemotherapy.

• - See Disease Characteristics.

• - No prior chemotherapy for recurrent disease.

• - No more than one prior chemotherapy regimen in the adjuvant setting.

• - At least 6 months since prior adjuvant chemotherapy.

Endocrine therapy.

• - Concurrent steroids allowed provided the dose is stable for at least 14 days before study entry.

Radiotherapy.

• - See Disease Characteristics.

• - At least 6 weeks since prior radiotherapy.

Surgery.

• - At least 2 weeks since prior major surgery.

Other.

• - H2 blockers and proton pump inhibitors allowed, unless they are CYP3A4 inducers or inhibitors.

• - At least 7 days since prior and no concurrent administration of any of the following CYP3A4 inhibitors: - Clarithromycin.

• - Erythromycin.

• - Troleandomycin.

• - Telithromycin.

• - Ciprofloxacin.

• - Norfloxacin.

• - Itraconazole.

• - Ketoconazole.

• - Voriconazole.

• - Fluconazole (≤150 mg/day allowed) - Nefazodone.

• - Fluovoxamine.

• - Delavirdine.

• - Nelfinavir.

• - Amprenavir.

• - Ritonavir.

• - Indinavir.

• - Saquinavir.

• - Lopinavir.

• - Verapamil.

• - Diltiazem.

• - Aprepitant.

• - Grapefruit or grapefruit juice.

• - Bitter orange.

• - At least 14 days since prior and no concurrent administration of any of the following CYP3A4 inducers: - Rifampin.

• - Rifabutin.

• - Rifapentine.

• - Efavirenz.

• - Nevirapine.

• - Hypericum perforatum (St. John's wort) - Modafinil.

• - At least 6 months since prior and no concurrent administration of amiodarone.

• - Antacids (e.g., mylanta, maalox, tums, rennies) must be administered ≥ 1 hour before and ≥ 1 hour after study drug.

• - At least 2 days since prior and no concurrent cimetidine.

• - No other concurrent anti-cancer agents.

- No other concurrent investigational therapy

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.