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

This study has been completed.
National Cancer Institute (NCI)
Information provided by:
Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:
First received: May 14, 2004
Last updated: January 28, 2010
Last verified: January 2010

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 Intervention Phase
Brain and Central Nervous System Tumors
Drug: leucovorin calcium
Drug: methotrexate
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Systemic High-Dose Methotrexate For The Treatment Of Glioblastoma Multiforme In Newly Diagnosed Patients With Measurable Disease

Resource links provided by NLM:

Further study details as provided by Eastern Cooperative Oncology Group:

Primary Outcome Measures:
  • Response rate (complete and partial) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Frequency of toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment: 36
Study Start Date: February 2005
Primary Completion Date: May 2007 (Final data collection date for primary outcome measure)
Detailed Description:



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


  • 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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


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


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


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


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


  • 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


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])


  • 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


  • No prior cranial irradiation
  • No prior radiotherapy for GBM


  • Recovered from prior surgery


  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00082797

  Show 65 Study Locations
Sponsors and Collaborators
Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
Study Chair: Stuart A. Grossman, MD Sidney Kimmel Comprehensive Cancer Center
Study Chair: Jana Portnow, MD Beckman Research Institute
  More Information

Responsible Party: Group Chair, Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier: NCT00082797     History of Changes
Other Study ID Numbers: CDR0000360834  E1F02 
Study First Received: May 14, 2004
Last Updated: January 28, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Eastern Cooperative Oncology Group:
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Nervous System Diseases
Neuroectodermal Tumors
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on May 24, 2016