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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00082797
• Other study ID #: CDR0000360834
• Secondary ID: E1F02
• Status: Completed
• Phase: Phase 2
• Start date: July 12, 2005

Study information

• Verified date: June 2023
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. primary completion date: May 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

Intervention

Drug:
• leucovorin calcium

• methotrexate

Locations

Country	Name	City	State
United States	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania
United States	Rush-Copley Cancer Care Center	Aurora	Illinois
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	St. Joseph Medical Center	Bloomington	Illinois
United States	Fairview Ridges Hospital	Burnsville	Minnesota
United States	Graham Hospital	Canton	Illinois
United States	Memorial Hospital	Carthage	Illinois
United States	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia
United States	Hematology and Oncology Associates	Chicago	Illinois
United States	Mercy Hospital and Medical Center	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	Swedish Covenant Hospital	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Fairview Southdale Hospital	Edina	Minnesota
United States	Eureka Community Hospital	Eureka	Illinois
United States	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota
United States	Galesburg Clinic	Galesburg	Illinois
United States	Galesburg Cottage Hospital	Galesburg	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Hopedale Medical Complex	Hopedale	Illinois
United States	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois
United States	Midwest Center for Hematology/Oncology	Joliet	Illinois
United States	Borgess Medical Center	Kalamazoo	Michigan
United States	Bronson Methodist Hospital	Kalamazoo	Michigan
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kewanee Hospital	Kewanee	Illinois
United States	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois
United States	McDonough District Hospital	Macomb	Illinois
United States	Minnesota Oncology Hematology, PA at Maplewood Cancer Center	Maplewood	Minnesota
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Saint Anthony Memorial Health Centers	Michigan City	Indiana
United States	Virginia Piper Cancer Institute at Abbott-Northwestern Hospital	Minneapolis	Minnesota
United States	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia
United States	Northwest Medical Specialist, PC	Niles	Illinois
United States	BroMenn Regional Medical Center	Normal	Illinois
United States	Community Cancer Center	Normal	Illinois
United States	Community Hospital of Ottawa	Ottawa	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois
United States	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	Peoria	Illinois
United States	Illinois Valley Community Hospital	Peru	Illinois
United States	Perry Memorial Hospital	Princeton	Illinois
United States	Hubert H. Humphrey Cancer Center at North Memorial Medical Center	Robbinsdale	Minnesota
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Park Nicollet Health Services	Saint Louis Park	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	Medical X-Ray Center, PC	Sioux Falls	South Dakota
United States	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota
United States	Hematology Oncology Associates - Skokie	Skokie	Illinois
United States	Hematology/Oncology of the North Shore at Gross Point Medical Center	Skokie	Illinois
United States	Midwest Cancer Research Group, Incorporated	Skokie	Illinois
United States	St. Margaret's Hospital	Spring Valley	Illinois
United States	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	Ridgeview Medical Center	Waconia	Minnesota
United States	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate (complete and partial)
Secondary	Frequency of toxicity