S0001 RT and Carmustine With or Without O6BG in Patients With New Glioblastoma Multiforme or Gliosarcoma

Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous System Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00017147
• Other study ID #: CDR0000068656
• Secondary ID: S0001U10CA032102
• Status: Completed
• Phase: Phase 3
• First received: June 6, 2001
• Last updated: January 28, 2013
• Start date: September 2001
• Est. completion date: November 2012

Study information

• Verified date: January 2013
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 183
• Est. completion date: November 2012
• Est. primary completion date: May 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Eye Neoplasms
• Glioblastoma
• Gliosarcoma
• Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous System
• Neoplasms

Intervention

Drug:
• carmustine
40 mg/m^2 IV over 1 hour on day 1 of each cycle 6 hours after O6-BG dose for experimental arm with O6=BG. 200 mg/m^2 IV over 1 hour on day 2 of each cycle for the active comparator arm.

Radiation:
• radiation therapy
5 days/week using one fraction per day and a dose of 180 cGy per fraction. Initial target volume is dose of 5040 cGy in 28 fractions with boost target volume of 1080 cGy in 6 fractions.

Drug:
• O6-Benzylguanine
120 mg/m^2 IV over 1 hour on day 1 of each cycle

Locations

Country	Name	City	State
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	Alaska Regional Hospital Cancer Center	Anchorage	Alaska
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	WellStar Cobb Hospital	Austell	Georgia
United States	Baton Rouge General Regional Cancer Center	Baton Rouge	Louisiana
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	St. Francis Hospital and Health Centers	Beech Grove	Indiana
United States	St. Joseph Hospital Community Cancer Center	Bellingham	Washington
United States	Mecosta County General Hospital	Big Rapids	Michigan
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Deaconess Billings Clinic - Downtown	Billings	Montana
United States	Deaconess Billings Clinic Cancer Center	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare	Billings	Montana
United States	Bozeman Deaconess Hospital	Bozeman	Montana
United States	Internal Medicine Associates of Bozeman	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	St. James Community Hospital	Butte	Montana
United States	St. Francis Medical Center	Cape Girardeau	Missouri
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	University of Illinois at Chicago Cancer Center	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago Westside Hospital	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Memorial Hospital Cancer Center	Colorado Springs	Colorado
United States	CCOP - Columbus	Columbus	Ohio
United States	Doctors Hospital at Ohio Health	Columbus	Ohio
United States	Grant Riverside Cancer Services	Columbus	Ohio
United States	Mount Carmel West Hospital	Columbus	Ohio
United States	Riverside Methodist Hospital Cancer Care	Columbus	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Genesis Medical Center - West Campus	Davenport	Iowa
United States	Genesis Regional Cancer Center at Genesis Medical Center	Davenport	Iowa
United States	CCOP - Dayton	Dayton	Ohio
United States	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio
United States	Good Samaritan Hospital	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Samaritan North Cancer Care Center	Dayton	Ohio
United States	Veterans Affairs Medical Center - Dayton	Dayton	Ohio
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Grady Memorial Hospital	Delaware	Ohio
United States	St. Anthony Central Hospital	Denver	Colorado
United States	University of Colorado Cancer Center at University of Colorado Health Sciences Center	Denver	Colorado
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Cancer Center of Kansas, P.A. - El Dorado	El Dorado	Kansas
United States	North Bay Cancer Center	Fairfield	California
United States	St. Francis Hospital	Federal Way	Washington
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Gape Girardeau	Missouri
United States	Legacy Mount Hood Medical Center	Glesham	Oregon
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Mercy Medical Center	Grand Rapids	Michigan
United States	Metropolitan Hospital	Grand Rapids	Michigan
United States	Spectrum Health Cancer Care - Butterworth Campus	Grand Rapids	Michigan
United States	Great Falls Clinic	Great Falls	Montana
United States	Sletten Regional Cancer Institute	Great Falls	Montana
United States	North Colorado Medical Center	Greeley	Colorado
United States	St. Peter's Hospital	Helena	Montana
United States	Holland Community Hospital	Holland	Michigan
United States	Hematology Oncology Associates of Eastern Idaho	Idaho Falls	Idaho
United States	Community Oncology Group - Independence	Independence	Ohio
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	Freeman Cancer Institute at Freeman Health System	Joplin	Missouri
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology	Kalispell	Montana
United States	CCOP - Kansas City	Kansas City	Missouri
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Veterans Affairs Medical Center - Kansas City	Kansas City	Kansas
United States	Good Samaritan Health Systems	Kearney	Nebraska
United States	Charles F. Kettering Memorial Hospital	Kettering	Ohio
United States	Cancer Center of Kansas - Kingman	Kingman	Kansas
United States	Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center	Kingsport	Tennessee
United States	Wilford Hall Medical Center	Lackland AFB	Texas
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	Southwest Medical Center	Liberal	Kansas
United States	McKee Medical Center	Loveland	Colorado
United States	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia
United States	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio
United States	Middletown Regional Hospital	Middletown	Ohio
United States	Eastern Montana Cancer Center	Miles City	Montana
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
United States	Community Medical Center	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Good Samaritan Regional Health Center	Mt. Vernon	Illinois
United States	Skagit Valley Hospital Cancer Care Center	Mt. Vernon	Washington
United States	Hackley Hospital	Muskegon	Michigan
United States	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana
United States	Medical Center of Louisiana - New Orleans	New Orleans	Louisiana
United States	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Capital Medical Center	Olympia	Washington
United States	Cancer Center of Kansas, P.A. - Parsons	Parsons	Kansas
United States	West Florida Cancer Institute at West Florida Hospital - Pensacola	Pensacola	Florida
United States	Northern Michigan Hospital	Petoskey	Michigan
United States	Banner Good Samaritan Medical Center	Phoenix	Arizona
United States	Banner Thunderbird Medical Center	Phoenix	Arizona
United States	CCOP - Western Regional, Arizona	Phoenix	Arizona
United States	St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Institute of Oncology at Vilnius University	Portland	Oregon
United States	Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Pratt Cancer Center of Kansas	Pratt	Kansas
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	William Beaumont Hospital - Royal Oak Campus	Royal Oak	Michigan
United States	Salem Hospital Regional Cancer Center	Salem	Oregon
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Salina Regional Health Center	Salina	Kansas
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	North Puget Oncology at United General Hospital	Sedro-Wooley	Washington
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Community Hospital of Springfield and Clark County	Springfield	Ohio
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	Mercy Medical Center Oncology Unit	Springfield	Ohio
United States	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois
United States	St. John's Regional Health Center	Springfield	Missouri
United States	CCOP - St. Louis-Cape Girardeau	St. Louis	Missouri
United States	David C. Pratt Cancer Center at St. John's Mercy	St. Louis	Missouri
United States	Allenmore Hospital	Tacoma	Washington
United States	CCOP - Northwest	Tacoma	Washington
United States	St. Clare Hospital	Tacoma	Washington
United States	CCOP - Scott and White Hospital	Temple	Texas
United States	St. Francis Comprehensive Cancer Center	Topeka	Kansas
United States	Stormont-Vail Cancer Center	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio
United States	Legacy Meridian Park Hospital	Tualatin	Oregon
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Central Washington Hospital	Wenatchee	Washington
United States	Wenatchee Valley Clinic	Wenatchee	Washington
United States	Mount Carmel Cancer Services at Mount Carmel St. Ann's Hospital	Westerville	Ohio
United States	St. Anthony North Hospital	Westminster	Colorado
United States	Exempla Lutheran Medical Center	Wheat Ridge	Colorado
United States	Associates in Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas, P.A.	Wichita	Kansas
United States	Cancer Center of Kansas, P.A. - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	Cleveland Clinic - Wooster	Wooster	Ohio
United States	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio
United States	Genesis - Good Samaritan Hospital	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

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.

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( — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival		assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5	No
Secondary	Progression-free survival		assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5	No
Secondary	Time to treatment failure		assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5	No
Secondary	Toxicity		assessed weekly for 42 weeks	Yes