Lapatinib in Treating Patients With Recurrent Glioblastoma Multiforme

• Status: Completed
• Trial end date: 2007-11-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Collaborator: NCIC Clinical Trials Group
• Treatments: Lapatinib

Criteria

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