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

Sponsor

Eastern Cooperative Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00082797

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

0.6

Patients Per Site

Study Details

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

Anticipated 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 :

Feb 1, 2005

Actual Primary Completion Date :

May 1, 2007

Outcome Measures

Primary Outcome Measures

Response rate (complete and partial) []

Secondary Outcome Measures

Frequency of toxicity []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60507
2	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
3	Graham Hospital	Canton	Illinois	United States	61520
4	Memorial Hospital	Carthage	Illinois	United States	62321
5	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
6	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
7	University of Illinois Cancer Center	Chicago	Illinois	United States	60612-7243
8	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois	United States	60612
9	Mercy Hospital and Medical Center	Chicago	Illinois	United States	60616
10	Swedish Covenant Hospital	Chicago	Illinois	United States	60625
11	Eureka Community Hospital	Eureka	Illinois	United States	61530
12	Galesburg Clinic	Galesburg	Illinois	United States	61401
13	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
14	Mason District Hospital	Havana	Illinois	United States	62644
15	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
16	Midwest Center for Hematology/Oncology	Joliet	Illinois	United States	60432
17	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
18	Kewanee Hospital	Kewanee	Illinois	United States	61443
19	North Shore Oncology and Hematology Associates, Limited - Libertyville	Libertyville	Illinois	United States	60048
20	McDonough District Hospital	Macomb	Illinois	United States	61455
21	Northwest Medical Specialist, PC	Niles	Illinois	United States	60714
22	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
23	Community Cancer Center	Normal	Illinois	United States	61761
24	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
25	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
26	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
27	Proctor Hospital	Peoria	Illinois	United States	61614
28	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
29	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
30	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
31	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
32	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
33	Perry Memorial Hospital	Princeton	Illinois	United States	61356
34	Swedish-American Regional Cancer Center	Rockford	Illinois	United States	61104-2315
35	Hematology Oncology Associates - Skokie	Skokie	Illinois	United States	60076
36	Hematology/Oncology of the North Shore at Gross Point Medical Center	Skokie	Illinois	United States	60076
37	Midwest Cancer Research Group, Incorporated	Skokie	Illinois	United States	60077
38	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
39	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
40	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
41	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
42	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
43	Borgess Medical Center	Kalamazooaa	Michigan	United States	49001
44	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
45	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
46	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
47	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
48	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
49	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
50	Minnesota Oncology Hematology, PA at Maplewood Cancer Center	Maplewood	Minnesota	United States	55109
51	Virginia Piper Cancer Institute at Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
52	Hubert H. Humphrey Cancer Center at North Memorial Medical Center	Robbinsdale	Minnesota	United States	55422-2900
53	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
54	Park Nicollet Health Services	St. Louis Park	Minnesota	United States	55416
55	United Hospital	St. Paul	Minnesota	United States	55102
56	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
57	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
58	Case Comprehensive Cancer Center	Cleveland	Ohio	United States	44106
59	Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest	Allentown	Pennsylvania	United States	18105
60	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
61	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
62	Sioux Valley Hospital and University of South Dakota Medical Center	Sioux Falls	South Dakota	United States	57117-5039
63	West Virginia University - Robert C. Byrd Health Sciences Center - Charleston Division	Charleston	West Virginia	United States	25304
64	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia	United States	26506
65	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449

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