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

June 14, 2023 updated by: Eastern Cooperative Oncology Group

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

36

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Aurora, Illinois, United States, 60507
        • Rush-Copley Cancer Care Center
      • Bloomington, Illinois, United States, 61701
        • St. Joseph Medical Center
      • Canton, Illinois, United States, 61520
        • Graham Hospital
      • Carthage, Illinois, United States, 62321
        • Memorial Hospital
      • Chicago, Illinois, United States, 60611-3013
        • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
      • Chicago, Illinois, United States, 60612-7243
        • University of Illinois Cancer Center
      • Chicago, Illinois, United States, 60625
        • Swedish Covenant Hospital
      • Chicago, Illinois, United States, 60611
        • Hematology and Oncology Associates
      • Chicago, Illinois, United States, 60612
        • Veterans Affairs Medical Center - Chicago Westside Hospital
      • Chicago, Illinois, United States, 60616
        • Mercy Hospital and Medical Center
      • Eureka, Illinois, United States, 61530
        • Eureka Community Hospital
      • Galesburg, Illinois, United States, 61401
        • Galesburg Cottage Hospital
      • Galesburg, Illinois, United States, 61401
        • Galesburg Clinic
      • Havana, Illinois, United States, 62644
        • Mason District Hospital
      • Hopedale, Illinois, United States, 61747
        • Hopedale Medical Complex
      • Joliet, Illinois, United States, 60435
        • Joliet Oncology-Hematology Associates, Limited - West
      • Joliet, Illinois, United States, 60432
        • Midwest Center for Hematology/Oncology
      • Kewanee, Illinois, United States, 61443
        • Kewanee Hospital
      • Libertyville, Illinois, United States, 60048
        • North Shore Oncology and Hematology Associates, Limited - Libertyville
      • Macomb, Illinois, United States, 61455
        • Mcdonough District Hospital
      • Niles, Illinois, United States, 60714
        • Northwest Medical Specialist, PC
      • Normal, Illinois, United States, 61761
        • Bromenn Regional Medical Center
      • Normal, Illinois, United States, 61761
        • Community Cancer Center
      • Ottawa, Illinois, United States, 61350
        • Community Hospital of Ottawa
      • Ottawa, Illinois, United States, 61350
        • Oncology Hematology Associates of Central Illinois, PC - Ottawa
      • Pekin, Illinois, United States, 61554
        • Cancer Treatment Center at Pekin Hospital
      • Peoria, Illinois, United States, 61636
        • Methodist Medical Center of Illinois
      • Peoria, Illinois, United States, 61614
        • Proctor Hospital
      • Peoria, Illinois, United States, 61637
        • OSF St. Francis Medical Center
      • Peoria, Illinois, United States, 61615
        • CCOP - Illinois Oncology Research Association
      • Peoria, Illinois, United States, 61615
        • Oncology Hematology Associates of Central Illinois, PC - Peoria
      • Peru, Illinois, United States, 61354
        • Illinois Valley Community Hospital
      • Princeton, Illinois, United States, 61356
        • Perry Memorial Hospital
      • Rockford, Illinois, United States, 61104-2315
        • Swedish-American Regional Cancer Center
      • Skokie, Illinois, United States, 60076
        • Hematology Oncology Associates - Skokie
      • Skokie, Illinois, United States, 60077
        • Midwest Cancer Research Group, Incorporated
      • Skokie, Illinois, United States, 60076
        • Hematology/Oncology of the North Shore at Gross Point Medical Center
      • Spring Valley, Illinois, United States, 61362
        • St. Margaret's Hospital
      • Urbana, Illinois, United States, 61801
        • Carle Cancer Center at Carle Foundation Hospital
      • Urbana, Illinois, United States, 61801
        • CCOP - Carle Cancer Center
    • Indiana
      • Michigan City, Indiana, United States, 46360
        • Saint Anthony Memorial Health Centers
    • Maryland
      • Baltimore, Maryland, United States, 21231-2410
        • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Michigan
      • Kalamazoo, Michigan, United States, 49007
        • Bronson Methodist Hospital
      • Kalamazoo, Michigan, United States, 49001
        • Borgess Medical Center
      • Kalamazoo, Michigan, United States, 49007-3731
        • West Michigan Cancer Center
    • Minnesota
      • Burnsville, Minnesota, United States, 55337
        • Fairview Ridges Hospital
      • Coon Rapids, Minnesota, United States, 55433
        • Mercy and Unity Cancer Center at Mercy Hospital
      • Edina, Minnesota, United States, 55435
        • Fairview Southdale Hospital
      • Fridley, Minnesota, United States, 55432
        • Mercy and Unity Cancer Center at Unity Hospital
      • Maplewood, Minnesota, United States, 55109
        • Minnesota Oncology Hematology, PA at Maplewood Cancer Center
      • Minneapolis, Minnesota, United States, 55407
        • Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
      • Robbinsdale, Minnesota, United States, 55422-2900
        • Hubert H. Humphrey Cancer Center at North Memorial Medical Center
      • Saint Louis Park, Minnesota, United States, 55416
        • CCOP - Metro-Minnesota
      • Saint Louis Park, Minnesota, United States, 55416
        • Park Nicollet Health Services
      • Saint Paul, Minnesota, United States, 55102
        • United Hospital
      • Waconia, Minnesota, United States, 55387
        • Ridgeview Medical Center
      • Woodbury, Minnesota, United States, 55125
        • Minnesota Oncology Hematology, PA - Woodbury
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Comprehensive Cancer Center
    • Pennsylvania
      • Allentown, Pennsylvania, United States, 18105
        • Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Avera Cancer Institute
      • Sioux Falls, South Dakota, United States, 57117-5039
        • Sioux Valley Hospital and University of South Dakota Medical Center
      • Sioux Falls, South Dakota, United States, 57105
        • Medical X-Ray Center, PC
    • West Virginia
      • Charleston, West Virginia, United States, 25304
        • West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division
      • Morgantown, West Virginia, United States, 26506
        • Mary Babb Randolph Cancer Center at West Virginia University Hospitals
    • Wisconsin
      • Marshfield, Wisconsin, United States, 54449
        • Marshfield Clinic - Marshfield Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Response rate (complete and partial)

Secondary Outcome Measures

Outcome Measure
Frequency of toxicity

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eastern Cooperative Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 12, 2005

Primary Completion (Actual)

May 1, 2007

Study Registration Dates

First Submitted

May 14, 2004

First Submitted That Met QC Criteria

May 18, 2004

First Posted (Estimated)

May 19, 2004

Study Record Updates

Last Update Posted (Actual)

June 15, 2023

Last Update Submitted That Met QC Criteria

June 14, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000360834
  • E1F02

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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