High-Dose Methotrexate and Leucovorin in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Study Overview
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Brief Summary
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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.

Detailed Description
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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 then receive standard radiotherapy with or without chemotherapy. Patients with disease progression proceed to standard radiotherapy with or without chemotherapy upon stopping methotrexate therapy. 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.

Official Title
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A Phase II Study Of Systemic High-Dose Methotrexate For The Treatment Of Glioblastoma Multiforme In Newly Diagnosed Patients With Measurable Disease

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: leucovorin calcium
* Drug: methotrexate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: leucovorin calcium|nan|
|Drug: methotrexate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete and partial) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of toxicity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma