RATIONALE: Drugs used in chemotherapy, such as methotrexate, work in different ways to stop tumor cells from dividing so they stop growing or die. Leucovorin may decrease side effects caused by high-dose methotrexate.

PURPOSE: This phase II trial is studying how well giving high-dose methotrexate together with leucovorin works in treating patients with newly diagnosed glioblastoma multiforme.

Condition	Treatment or Intervention	Phase
adult glioblastoma adult giant cell glioblastoma adult gliosarcoma	Drug: leucovorin calcium  Drug: methotrexate  Procedure: chemotherapy  Procedure: drug modulation  Procedure: high-dose chemotherapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the response in patients with newly diagnosed glioblastoma multiforme treated with high-dose methotrexate and leucovorin calcium.

Secondary

• Determine the acute toxicity of this regimen in these patients.
• Determine the duration of survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive high-dose methotrexate IV over 4 hours on day 1 and oral or IV leucovorin calcium every 6 hours beginning on day 2 and continuing until blood methotrexate levels are acceptable. Treatment repeats every 14 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed at 30 days and then every 2 months for up to 2 years.

PROJECTED ACCRUAL: A total of 19-36 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme (GBM)
• Supratentorial grade IV disease
• Measurable and contrast-enhancing disease ≥ 1 cm by CT scan or MRI
• No radiographic evidence of ascites or pleural effusion

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3

Hepatic

• SGOT ≤ 4.0 times upper limit of normal
• Bilirubin ≤ 2.0 mg/dL

Renal

• Creatinine ≤ 2.0 mg/dL
• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• No uncontrolled hypertension
• No unstable angina
• No symptomatic congestive heart failure
• No uncontrolled cardiac arrhythmia
• No myocardial infarction within the past 6 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to achieve hydration
• No diabetes insipidus
• No known hypersensitivity to methotrexate or leucovorin calcium
• No concurrent serious infection or medical illness that would preclude study participation
• No other malignancy within the past 2 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for GBM
• No prior administration of any of the following biologic agents for GBM:
• Immunotoxins
• Immunoconjugates
• Antisense therapy
• Peptide receptor antagonists
• Interferons
• Interleukins
• Tumor-infiltrating lymphocytes
• Lymphokine-activated killer cells
• Gene therapy
• No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

Chemotherapy

• No prior chemotherapy for GBM
• No other concurrent chemotherapy

Endocrine therapy

• Prior glucocorticoid therapy allowed
• No prior hormonal therapy for GBM
• Patients must be maintained on a stable corticosteroid regimen for at least 1 week

Radiotherapy

• No prior cranial irradiation
• No prior radiotherapy for GBM

Surgery

• Recovered from prior surgery

Other

• At least 1 week since prior treatment with any of the following:
• Salicylates
• Non-steroidal anti-inflammatory drugs
• Sulfonamide medications
• Vitamin C
• No other concurrent investigational agents

Study chairs or principal investigators

Stuart A. Grossman, MD,  Study Chair,  Sidney Kimmel Cancer Center   
Jana Portnow, MD,  Beckman Research Institute   

Study ID Numbers:  CDR0000360834; ECOG-E1F02; NCT00082797
Record last reviewed:  February 2005
Last Updated:  March 3, 2005
Record first received:  May 14, 2004
ClinicalTrials.gov Identifier:  NCT00082797
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08