Lapatinib in Treating Patients With Recurrent Glioblastoma Multiforme

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