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Radiation Therapy and Carmustine With or Without O6-Benzylguanine in Treating Patients With Newly Diagnosed Glioblastoma Multiforme or Gliosarcoma
This study is ongoing, but not recruiting participants.
First Received: June 6, 2001   Last Updated: February 6, 2009   History of Changes
Sponsor: Southwest Oncology Group
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00017147
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. O6-benzylguanine may help carmustine kill more tumor cells by making tumor cells more sensitive to the drug. It is not yet known whether radiation therapy and carmustine are more effective with or without O6-benzylguanine.

PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy plus carmustine with or without O6-benzylguanine in treating patients who have newly diagnosed glioblastoma multiforme or gliosarcoma.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: O6-benzylguanine
Drug: carmustine
Radiation: radiation therapy
Phase III

Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
Official Title: A Phase III Study of Radiation Therapy (RT) and O6-Benzylguanine (O6-BG) Plus BCNU Versus RT and BCNU Alone for Newly Diagnosed Glioblastoma Multiforme (GBM) and Gliosarcoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Designated as safety issue: No ]
  • Time to treatment failure [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Study Start Date: September 2001
Detailed Description:

OBJECTIVES:

  • Compare the overall survival, failure-free survival, and progression-free survival of patients with newly diagnosed glioblastoma multiforme or gliosarcoma treated with radiotherapy and carmustine with or without O6-benzylguanine.
  • Compare the frequency and severity of toxic effects of these regimens in these patients.
  • Correlate the survival of these patients with the expression of O6-alkylguanine-DNA alkyltransferase.

OUTLINE: This is a randomized study. Patients are stratified according to age (under 50 vs 50 and over), prior surgery (biopsy only vs resection), and Zubrod performance status (0-1 vs 2). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo radiotherapy daily 5 days a week over 7 weeks for a total of 34 fractions. Patients also receive chemotherapy comprising O6-benzylguanine IV over 1 hour followed 6 hours later by carmustine IV over 1 hour on day 1 of radiotherapy. Chemotherapy repeats every 6 weeks for a maximum of 7 courses in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients undergo radiotherapy as in arm I. Patients receive carmustine IV as in arm I.

Patients are followed at week 48, every 4 months for 1 year, and then every 6 months for 4 years.

PROJECTED ACCRUAL: A total of 375 patients will be accrued for this study within 5 years.

  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 or gliosarcoma

    • Biopsy or surgical resection within the past 28 days

      • MRI* with gadolinium performed before registration
      • Patients who undergo a simple biopsy only require preoperative MRI* with gadolinium
  • No more than 2 noncontiguous tumor sites based on T2-weighted MRI (in 3 dimensions)*
  • No prior radiotherapy-delivered cephalad to the interspace between the seventh cervical and the first thoracic vertebral body NOTE: *If an MRI is not medically feasible, patients may have a CT scan with contrast

PATIENT CHARACTERISTICS:

Age:

  • 18 and over

Performance status:

  • Zubrod 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Absolute neutrophil count at least 3,000/mm^3
  • Platelet count at least 100,000/mm^3
  • Hemoglobin at least 8 g/dL

Hepatic:

  • Bilirubin no greater than 2 times upper limit of normal (ULN)
  • SGOT/SGPT no greater than 2 times ULN
  • Alkaline phosphatase no greater than 2 times ULN
  • PT/PTT no greater than 1.2 times ULN

Renal:

  • Not specified

Cardiac:

  • No severe cardiac disease, including any of the following:

    • Uncontrolled arrhythmias or conduction defects
    • Major problems with edema (e.g., residual swelling in the legs from deep vein thrombosis)
    • Recent coronary artery disease
    • Poorly controlled hypertension (i.e., diastolic blood pressure greater than 110 mm Hg and/or systolic blood pressure greater than 180 mm Hg)

Pulmonary:

  • DLCO at least 70% of predicted
  • No severe pulmonary disease

Other:

  • HIV negative
  • No severe Cushing's syndrome
  • No known allergies to any of the study drugs
  • No major psychiatric illness
  • No poorly controlled diabetes complicated by steroid treatment
  • No other medical illness that cannot be adequately controlled or that would preclude study participation
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Not specified

Chemotherapy:

  • No prior chemotherapy
  • No other concurrent antitumor chemotherapy

Endocrine therapy:

  • No concurrent hormonal therapy except postmenopausal estrogen replacement therapy
  • Corticosteroids at stable or decreasing dose for tumor edema allowed

Radiotherapy:

  • See Disease Characteristics
  • No prior radiotherapy
  • No other concurrent radiotherapy (including intensity-modulated radiotherapy) to the index lesion(s)

Surgery:

  • See Disease Characteristics
  • No concurrent antitumor surgery

Other:

  • No other concurrent investigational drugs
  • No other concurrent antineoplastic drugs or therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00017147

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Locations
United States, Alaska
Alaska Regional Hospital Cancer Center
Anchorage, Alaska, United States, 99508
United States, Arizona
Banner Good Samaritan Medical Center
Phoenix, Arizona, United States, 85006
Banner Thunderbird Medical Center
Phoenix, Arizona, United States, 85306
CCOP - Western Regional, Arizona
Phoenix, Arizona, United States, 85006
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, United States, 85013
United States, California
North Bay Cancer Center
Fairfield, California, United States, 94533
United States, Colorado
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, United States, 80033
McKee Medical Center
Loveland, Colorado, United States, 80539
Memorial Hospital Cancer Center
Colorado Springs, Colorado, United States, 80909
North Colorado Medical Center
Greeley, Colorado, United States, 80631
St. Anthony Central Hospital
Denver, Colorado, United States, 80204
St. Anthony North Hospital
Westminster, Colorado, United States, 80030
University of Colorado Cancer Center at University of Colorado Health Sciences Center
Denver, Colorado, United States, 80217-3364
United States, Florida
West Florida Cancer Institute at West Florida Hospital - Pensacola
Pensacola, Florida, United States, 32514
United States, Georgia
CCOP - Atlanta Regional
Atlanta, Georgia, United States, 30342
Northside Hospital Cancer Center
Atlanta, Georgia, United States, 30342
Gwinnett Medical Center
Lawrenceville, Georgia, United States, 30045
Kennestone Cancer Center at Wellstar Kennestone Hospital
Marietta, Georgia, United States, 30060
Northeast Georgia Medical Center
Gainesville, Georgia, United States, 30501
Charles B. Eberhart Cancer Center at DeKalb Medical Center
Decatur, Georgia, United States, 30033
Piedmont Hospital
Atlanta, Georgia, United States, 30309
Saint Joseph's Hospital of Atlanta
Atlanta, Georgia, United States, 30342
Southern Regional Medical Center
Riverdale, Georgia, United States, 30274
WellStar Cobb Hospital
Austell, Georgia, United States, 30106
United States, Idaho
Hematology Oncology Associates of Eastern Idaho
Idaho Falls, Idaho, United States, 83404
United States, Illinois
University of Illinois at Chicago Cancer Center
Chicago, Illinois, United States, 60612
Good Samaritan Regional Health Center
Mt. Vernon, Illinois, United States, 62864
Regional Cancer Center at Memorial Medical Center
Springfield, Illinois, United States, 62781-0001
Saint Anthony's Hospital at Saint Anthony's Health Center
Alton, Illinois, United States, 62002
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, United States, 62526
Veterans Affairs Medical Center - Chicago Westside Hospital
Chicago, Illinois, United States, 60612
United States, Indiana
St. Francis Hospital and Health Centers
Beech Grove, Indiana, United States, 46107
United States, Iowa
Genesis Medical Center - West Campus
Davenport, Iowa, United States, 52804
Genesis Regional Cancer Center at Genesis Medical Center
Davenport, Iowa, United States, 52803
United States, Kansas
Associates in Womens Health
Wichita, Kansas, United States, 67203
Cancer Center of Kansas - Salina
Salina, Kansas, United States, 67042
Cancer Center of Kansas - Dodge City
Dodge City, Kansas, United States, 67801
Cancer Center of Kansas - Kingman
Kingman, Kansas, United States, 67068
Cancer Center of Kansas - Newton
Newton, Kansas, United States, 67114
Cancer Center of Kansas - Chanute
Chanute, Kansas, United States, 66720
Cancer Center of Kansas - Wellington
Wellington, Kansas, United States, 67152
Cancer Center of Kansas - Winfield
Winfield, Kansas, United States, 67156
Cancer Center of Kansas, P.A. - Wichita
Wichita, Kansas, United States, 67214
Cancer Center of Kansas, P.A. - El Dorado
El Dorado, Kansas, United States, 67042
Cancer Center of Kansas, P.A. - Parsons
Parsons, Kansas, United States, 67357
Cancer Center of Kansas, P.A.
Wichita, Kansas, United States, 67208
Southwest Medical Center
Liberal, Kansas, United States, 67901
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
Pratt Cancer Center of Kansas
Pratt, Kansas, United States, 67124
Salina Regional Health Center
Salina, Kansas, United States, 67401
CCOP - Wichita
Wichita, Kansas, United States, 67214
St. Francis Comprehensive Cancer Center
Topeka, Kansas, United States, 66606
Stormont-Vail Cancer Center
Topeka, Kansas, United States, 66604
Veterans Affairs Medical Center - Kansas City
Kansas City, Kansas, United States, 64128
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
Wesley Medical Center
Wichita, Kansas, United States, 67214
United States, Louisiana
Baton Rouge General Regional Cancer Center
Baton Rouge, Louisiana, United States, 70806
Mary Bird Perkins Cancer Center - Baton Rouge
Baton Rouge, Louisiana, United States, 70809
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, United States, 70112
Medical Center of Louisiana - New Orleans
New Orleans, Louisiana, United States, 70112
United States, Michigan
Battle Creek Health System Cancer Care Center
Battle Creek, Michigan, United States, 49017
CCOP - Grand Rapids
Grand Rapids, Michigan, United States, 49503
Hackley Hospital
Muskegon, Michigan, United States, 49443
Holland Community Hospital
Holland, Michigan, United States, 49423
Lacks Cancer Center at Saint Mary's Mercy Medical Center
Grand Rapids, Michigan, United States, 49503
Mecosta County General Hospital
Big Rapids, Michigan, United States, 49307
William Beaumont Hospital - Royal Oak Campus
Royal Oak, Michigan, United States, 48073
Munson Medical Center
Traverse City, Michigan, United States, 49684
Northern Michigan Hospital
Petoskey, Michigan, United States, 49770
Spectrum Health Cancer Care - Butterworth Campus
Grand Rapids, Michigan, United States, 49503
Metropolitan Hospital
Grand Rapids, Michigan, United States, 49506
United States, Mississippi
University of Mississippi Medical Center
Jackson, Mississippi, United States, 39216
United States, Missouri
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
CCOP - St. Louis-Cape Girardeau
St. Louis, Missouri, United States, 63141
David C. Pratt Cancer Center at St. John's Mercy
St. Louis, Missouri, United States, 63141
Freeman Cancer Institute at Freeman Health System
Joplin, Missouri, United States, 64804
Hulston Cancer Center at Cox Medical Center South
Springfield, Missouri, United States, 65807
Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
Gape Girardeau, Missouri, United States, 63701
St. Francis Medical Center
Cape Girardeau, Missouri, United States, 63701
St. John's Regional Health Center
Springfield, Missouri, United States, 65804
United States, Montana
Bozeman Deaconess Hospital
Bozeman, Montana, United States, 59715
CCOP - Montana Cancer Consortium
Billings, Montana, United States, 59101
Community Medical Center
Missoula, Montana, United States, 59801
Deaconess Billings Clinic - Downtown
Billings, Montana, United States, 59101
Deaconess Billings Clinic Cancer Center
Billings, Montana, United States, 59107
Eastern Montana Cancer Center
Miles City, Montana, United States, 59301
Glacier Oncology, PLLC
Kalispell, Montana, United States, 59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, United States, 59802
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, United States, 59101
Internal Medicine Associates of Bozeman
Bozeman, Montana, United States, 59715
Kalispell Medical Oncology
Kalispell, Montana, United States, 59901
Great Falls Clinic
Great Falls, Montana, United States, 59405
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, United States, 59802
Northern Rockies Radiation Oncology Center
Billings, Montana, United States, 59101
Sletten Regional Cancer Institute
Great Falls, Montana, United States, 59405
St. James Community Hospital
Butte, Montana, United States, 59701
St. Peter's Hospital
Helena, Montana, United States, 59601
St. Vincent Healthcare
Billings, Montana, United States, 59101
United States, Nebraska
Good Samaritan Health Systems
Kearney, Nebraska, United States, 68847
United States, New York
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
United States, Ohio
Mount Carmel Cancer Services at Mount Carmel St. Ann's Hospital
Westerville, Ohio, United States, 43081
Adena Regional Medical Center
Chillicothe, Ohio, United States, 54601
CCOP - Columbus
Columbus, Ohio, United States, 43215
CCOP - Dayton
Dayton, Ohio, United States, 45429
Charles F. Kettering Memorial Hospital
Kettering, Ohio, United States, 45429
Cleveland Clinic - Wooster
Wooster, Ohio, United States, 44691
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Community Hospital of Springfield and Clark County
Springfield, Ohio, United States, 45505
Community Oncology Group - Independence
Independence, Ohio, United States, 44131
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, United States, 45409
Doctors Hospital at Ohio Health
Columbus, Ohio, United States, 43228
Fairfield Medical Center
Lancaster, Ohio, United States, 43130
Genesis - Good Samaritan Hospital
Zanesville, Ohio, United States, 43701
Good Samaritan Hospital
Dayton, Ohio, United States, 45406
Grady Memorial Hospital
Delaware, Ohio, United States, 43015
Grandview Hospital
Dayton, Ohio, United States, 45405
Grant Riverside Cancer Services
Columbus, Ohio, United States, 43215
Mercy Medical Center Oncology Unit
Springfield, Ohio, United States, 45504
Middletown Regional Hospital
Middletown, Ohio, United States, 45044
Licking Memorial Cancer Care Program at Licking Memorial Hospital
Newark, Ohio, United States, 43055
Mount Carmel West Hospital
Columbus, Ohio, United States, 43222
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, United States, 43214
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, United States, 45385
Samaritan North Cancer Care Center
Dayton, Ohio, United States, 45415
Strecker Cancer Center at Marietta Memorial Hospital
Marietta, Ohio, United States, 45750
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, United States, 45373
Veterans Affairs Medical Center - Dayton
Dayton, Ohio, United States, 45428
United States, Oregon
CCOP - Columbia River Oncology Program
Portland, Oregon, United States, 97225
Institute of Oncology at Vilnius University
Portland, Oregon, United States, 97227
Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
Portland, Oregon, United States, 97210
Legacy Meridian Park Hospital
Tualatin, Oregon, United States, 97062
Legacy Mount Hood Medical Center
Glesham, Oregon, United States, 97030
Providence Cancer Center at Providence Portland Medical Center
Portland, Oregon, United States, 97213
Providence Milwaukie Hospital
Milwaukie, Oregon, United States, 97222
Providence St. Vincent Medical Center
Portland, Oregon, United States, 97225
Salem Hospital Regional Cancer Center
Salem, Oregon, United States, 97309
United States, Tennessee
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
Kingsport, Tennessee, United States, 37660
United States, Texas
Brooke Army Medical Center
Fort Sam Houston, Texas, United States, 78234
CCOP - Scott and White Hospital
Temple, Texas, United States, 76508
Wilford Hall Medical Center
Lackland AFB, Texas, United States, 78236
United States, Utah
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, United States, 84112
United States, Virginia
Danville Regional Medical Center
Danville, Virginia, United States, 24541
United States, Washington
Allenmore Hospital
Tacoma, Washington, United States, 98405
Cancer Care Northwest - Spokane South
Spokane, Washington, United States, 99202
Capital Medical Center
Olympia, Washington, United States, 98507
CCOP - Northwest
Tacoma, Washington, United States, 98405
North Puget Oncology at United General Hospital
Sedro-Wooley, Washington, United States, 98284
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98104
Group Health Central Hospital
Seattle, Washington, United States, 98104
Harborview Medical Center
Seattle, Washington, United States, 98104
Central Washington Hospital
Wenatchee, Washington, United States, 98801
Olympic Hematology and Oncology
Bremerton, Washington, United States, 98310
Skagit Valley Hospital Cancer Care Center
Mt. Vernon, Washington, United States, 98273
Southwest Washington Medical Center Cancer Center
Vancouver, Washington, United States, 98668
St. Clare Hospital
Tacoma, Washington, United States, 98499
St. Francis Hospital
Federal Way, Washington, United States, 98003
St. Joseph Hospital Community Cancer Center
Bellingham, Washington, United States, 98225
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Seattle, Washington, United States, 98114
University Cancer Center at University of Washington Medical Center
Seattle, Washington, United States, 98195
Wenatchee Valley Clinic
Wenatchee, Washington, United States, 98801
United States, Wyoming
Welch Cancer Center
Sheridan, Wyoming, United States, 82801
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Investigator: Deborah T. Blumenthal, MD University of Utah
Investigator: Alexander M. Spence, MD University of Washington
Investigator: Keith J. Stelzer, MD, PhD Celilo Cancer Center at Mid-Columbia Medical Center
  More Information

Additional Information:
Publications:
Blumenthal DT, Wade M, Rankin CJ, et al.: MGMT methylation in newly-diagnosed glioblastoma multiforme (GBM): from the S0001 phase III study of radiation therapy (RT) and O6-benzylguanine, (O6BG) plus BCNU versus RT and BCNU alone for newly diagnosed GBM. [Abstract] J Clin Oncol 24 (Suppl 18): A-1512, 2006.
Quezado M, Ronchetti R, Rapkiewicz A, Santi M, Blumenthal DT, Rushing EJ. Chromogenic in situ hybridization accurately identifies EGFR amplification in small cell glioblastoma multiforme, a common subtype of primary GBM. Clin Neuropathol. 2005 Jul-Aug;24(4):163-9.

Study ID Numbers: CDR0000068656, SWOG-S0001
Study First Received: June 6, 2001
Last Updated: February 6, 2009
ClinicalTrials.gov Identifier: NCT00017147     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Glioblastoma
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Astrocytoma
Antineoplastic Agents
Carmustine
Nervous System Diseases
Neoplasms, Nerve Tissue
Enzyme Inhibitors
Central Nervous System Neoplasms
Pharmacologic Actions
Neuroectodermal Tumors
Neoplasms
Neoplasms by Site
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
O(6)-benzylguanine
Antineoplastic Agents, Alkylating
Glioma
Gliosarcoma
Neoplasms, Neuroepithelial
Alkylating Agents
Nervous System Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 22, 2009