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

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ClinicalTrials.gov Identifier: NCT00082797

Recruitment Status : Completed

First Posted : May 19, 2004

Last Update Posted : January 29, 2010

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by:

Eastern Cooperative Oncology Group

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors	Drug: leucovorin calcium Drug: methotrexate	Phase 2

Detailed Description:

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.

Study Design


Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	36 participants
Masking:	None (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
Study Start Date :	February 2005
Actual Primary Completion Date :	May 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Leucovorin Methotrexate Leucovorin calcium

Genetic and Rare Diseases Information Center resources: Glioblastoma Gliosarcoma Glioma Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

Response rate (complete and partial)

Secondary Outcome Measures :

Frequency of toxicity

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00082797

Show 65 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators


Study Chair:	Stuart A. Grossman, MD	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Chair:	Jana Portnow, MD	City of Hope Comprehensive Cancer Center

More Information


Responsible Party:	Group Chair, Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00082797 History of Changes
Other Study ID Numbers:	CDR0000360834 E1F02
First Posted:	May 19, 2004 Key Record Dates
Last Update Posted:	January 29, 2010
Last Verified:	January 2010

Keywords provided by Eastern Cooperative Oncology Group:


adult glioblastoma adult giant cell glioblastoma adult gliosarcoma

Additional relevant MeSH terms:


Glioblastoma Nervous System Neoplasms Central Nervous System Neoplasms Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Nervous System Diseases Methotrexate	Levoleucovorin Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents

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