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

Sponsor:	Eastern Cooperative Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00082797

Purpose

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 II

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:

MedlinePlus related topics: Cancer

Drug Information available for: Leucovorin Methotrexate Citrovorum factor Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

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:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

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)

Investigators

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

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

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:

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
Leucovorin

Levoleucovorin
Methotrexate
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Antidotes
Protective Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Therapeutic Uses
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on February 12, 2012