Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous SystemPhase 3NCT00017147
S0001 RT and Carmustine With or Without O6BG in Patients With New Glioblastoma Multiforme or Gliosarcoma
A Phase 3 study testing carmustine, radiation therapy and O6-Benzylguanine in people with Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous System, run by SWOG Cancer Research Network at 163 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous System
- What is being tested?
- carmustine, radiation therapy and O6-Benzylguanine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 183 participants
- Where
- 163 sitesUnited States
- Study dates
- Sep 2001to Nov 2012
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
163 sites in 1 country.
163 sites in 1 country
United States163 sites
Saint Anthony's Hospital at Saint Anthony's Health Center
Alton, Illinois, 62002
Alaska Regional Hospital Cancer Center
Anchorage, Alaska, 99508
Piedmont Hospital
Atlanta, Georgia, 30309
CCOP - Atlanta Regional
Atlanta, Georgia, 30342
Northside Hospital Cancer Center
Atlanta, Georgia, 30342
Saint Joseph's Hospital of Atlanta
Atlanta, Georgia, 30342
WellStar Cobb Hospital
Austell, Georgia, 30106
Baton Rouge General Regional Cancer Center
Baton Rouge, Louisiana, 70806
Mary Bird Perkins Cancer Center - Baton Rouge
Baton Rouge, Louisiana, 70809
Battle Creek Health System Cancer Care Center
Battle Creek, Michigan, 49017
St. Francis Hospital and Health Centers
Beech Grove, Indiana, 46107
St. Joseph Hospital Community Cancer Center
Bellingham, Washington, 98225
Mecosta County General Hospital
Big Rapids, Michigan, 49307
CCOP - Montana Cancer Consortium
Billings, Montana, 59101
Deaconess Billings Clinic - Downtown
Billings, Montana, 59101
Hematology-Oncology Centers of the Northern Rockies - Billings
Billings, Montana, 59101
Northern Rockies Radiation Oncology Center
Billings, Montana, 59101
St. Vincent Healthcare
Billings, Montana, 59101
Deaconess Billings Clinic Cancer Center
Billings, Montana, 59107
Bozeman Deaconess Hospital
Bozeman, Montana, 59715
Internal Medicine Associates of Bozeman
Bozeman, Montana, 59715
Olympic Hematology and Oncology
Bremerton, Washington, 98310
St. James Community Hospital
Butte, Montana, 59701
St. Francis Medical Center
Cape Girardeau, Missouri, 63701
Cancer Center of Kansas - Chanute
Chanute, Kansas, 66720
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, 28233
University of Illinois at Chicago Cancer Center
Chicago, Illinois, 60612
Veterans Affairs Medical Center - Chicago Westside Hospital
Chicago, Illinois, 60612
Adena Regional Medical Center
Chillicothe, Ohio, 54601
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195
Memorial Hospital Cancer Center
Colorado Springs, Colorado, 80909
Riverside Methodist Hospital Cancer Care
Columbus, Ohio, 43214
CCOP - Columbus
Columbus, Ohio, 43215
Grant Riverside Cancer Services
Columbus, Ohio, 43215
Mount Carmel West Hospital
Columbus, Ohio, 43222
Doctors Hospital at Ohio Health
Columbus, Ohio, 43228
Danville Regional Medical Center
Danville, Virginia, 24541
Genesis Regional Cancer Center at Genesis Medical Center
Davenport, Iowa, 52803
Genesis Medical Center - West Campus
Davenport, Iowa, 52804
Grandview Hospital
Dayton, Ohio, 45405
Good Samaritan Hospital
Dayton, Ohio, 45406
David L. Rike Cancer Center at Miami Valley Hospital
Dayton, Ohio, 45409
Samaritan North Cancer Care Center
Dayton, Ohio, 45415
Veterans Affairs Medical Center - Dayton
Dayton, Ohio, 45428
CCOP - Dayton
Dayton, Ohio, 45429
Charles B. Eberhart Cancer Center at DeKalb Medical Center
Decatur, Georgia, 30033
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, 62526
Grady Memorial Hospital
Delaware, Ohio, 43015
St. Anthony Central Hospital
Denver, Colorado, 80204
University of Colorado Cancer Center at University of Colorado Health Sciences Center
Denver, Colorado, 80217-3364
Cancer Center of Kansas - Dodge City
Dodge City, Kansas, 67801
Cancer Center of Kansas, P.A. - El Dorado
El Dorado, Kansas, 67042
North Bay Cancer Center
Fairfield, California, 94533
St. Francis Hospital
Federal Way, Washington, 98003
Brooke Army Medical Center
Fort Sam Houston, Texas, 78234
Northeast Georgia Medical Center
Gainesville, Georgia, 30501
Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
Gape Girardeau, Missouri, 63701
Legacy Mount Hood Medical Center
Glesham, Oregon, 97030
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, 27534
CCOP - Grand Rapids
Grand Rapids, Michigan, 49503
Lacks Cancer Center at Saint Mary's Mercy Medical Center
Grand Rapids, Michigan, 49503
Spectrum Health Cancer Care - Butterworth Campus
Grand Rapids, Michigan, 49503
Metropolitan Hospital
Grand Rapids, Michigan, 49506
Great Falls Clinic
Great Falls, Montana, 59405
Sletten Regional Cancer Institute
Great Falls, Montana, 59405
North Colorado Medical Center
Greeley, Colorado, 80631
St. Peter's Hospital
Helena, Montana, 59601
Holland Community Hospital
Holland, Michigan, 49423
Hematology Oncology Associates of Eastern Idaho
Idaho Falls, Idaho, 83404
Community Oncology Group - Independence
Independence, Ohio, 44131
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Freeman Cancer Institute at Freeman Health System
Joplin, Missouri, 64804
Glacier Oncology, PLLC
Kalispell, Montana, 59901
Kalispell Medical Oncology
Kalispell, Montana, 59901
Veterans Affairs Medical Center - Kansas City
Kansas City, Kansas, 64128
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, 66160
CCOP - Kansas City
Kansas City, Missouri, 64131
Good Samaritan Health Systems
Kearney, Nebraska, 68847
Charles F. Kettering Memorial Hospital
Kettering, Ohio, 45429
Cancer Center of Kansas - Kingman
Kingman, Kansas, 67068
Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
Kingsport, Tennessee, 37660
Wilford Hall Medical Center
Lackland Air Force Base, Texas, 78236
Fairfield Medical Center
Lancaster, Ohio, 43130
Gwinnett Medical Center
Lawrenceville, Georgia, 30045
Southwest Medical Center
Liberal, Kansas, 67901
McKee Medical Center
Loveland, Colorado, 80539
Kennestone Cancer Center at Wellstar Kennestone Hospital
Marietta, Georgia, 30060
Strecker Cancer Center at Marietta Memorial Hospital
Marietta, Ohio, 45750
Middletown Regional Hospital
Middletown, Ohio, 45044
Eastern Montana Cancer Center
Miles City, Montana, 59301
Providence Milwaukie Hospital
Milwaukie, Oregon, 97222
Community Medical Center
Missoula, Montana, 59801
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
Missoula, Montana, 59802
Montana Cancer Specialists at Montana Cancer Center
Missoula, Montana, 59802
Good Samaritan Regional Health Center
Mount Vernon, Illinois, 62864
Skagit Valley Hospital Cancer Care Center
Mount Vernon, Washington, 98273
Hackley Hospital
Muskegon, Michigan, 49443
MBCCOP - LSU Health Sciences Center
New Orleans, Louisiana, 70112
Medical Center of Louisiana - New Orleans
New Orleans, Louisiana, 70112
Licking Memorial Cancer Care Program at Licking Memorial Hospital
Newark, Ohio, 43055
Cancer Center of Kansas - Newton
Newton, Kansas, 67114
Capital Medical Center
Olympia, Washington, 98507
Cancer Center of Kansas, P.A. - Parsons
Parsons, Kansas, 67357
West Florida Cancer Institute at West Florida Hospital - Pensacola
Pensacola, Florida, 32514
Northern Michigan Hospital
Petoskey, Michigan, 49770
Banner Good Samaritan Medical Center
Phoenix, Arizona, 85006
CCOP - Western Regional, Arizona
Phoenix, Arizona, 85006
St. Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
Banner Thunderbird Medical Center
Phoenix, Arizona, 85306
Legacy Good Samaritan Hospital & Medical Center Comprehensive Cancer Center
Portland, Oregon, 97210
Providence Cancer Center at Providence Portland Medical Center
Portland, Oregon, 97213
CCOP - Columbia River Oncology Program
Portland, Oregon, 97225
Providence St. Vincent Medical Center
Portland, Oregon, 97225
Institute of Oncology at Vilnius University
Portland, Oregon, 97227
Pratt Cancer Center of Kansas
Pratt, Kansas, 67124
Southern Regional Medical Center
Riverdale, Georgia, 30274
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, 14642
William Beaumont Hospital - Royal Oak Campus
Royal Oak, Michigan, 48073
Salem Hospital Regional Cancer Center
Salem, Oregon, 97309
Cancer Center of Kansas - Salina
Salina, Kansas, 67042
Salina Regional Health Center
Salina, Kansas, 67401
Huntsman Cancer Institute at University of Utah
Salt Lake City, Utah, 84112
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98104
Group Health Central Hospital
Seattle, Washington, 98104
Harborview Medical Center
Seattle, Washington, 98104
Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
Seattle, Washington, 98114
University Cancer Center at University of Washington Medical Center
Seattle, Washington, 98195
North Puget Oncology at United General Hospital
Sedro-Woolley, Washington, 98284
Welch Cancer Center
Sheridan, Wyoming, 82801
Cancer Care Northwest - Spokane South
Spokane, Washington, 99202
Regional Cancer Center at Memorial Medical Center
Springfield, Illinois, 62781-0001
St. John's Regional Health Center
Springfield, Missouri, 65804
Hulston Cancer Center at Cox Medical Center South
Springfield, Missouri, 65807
Mercy Medical Center Oncology Unit
Springfield, Ohio, 45504
Community Hospital of Springfield and Clark County
Springfield, Ohio, 45505
CCOP - St. Louis-Cape Girardeau
St Louis, Missouri, 63141
David C. Pratt Cancer Center at St. John's Mercy
St Louis, Missouri, 63141
Allenmore Hospital
Tacoma, Washington, 98405
CCOP - Northwest
Tacoma, Washington, 98405
St. Clare Hospital
Tacoma, Washington, 98499
CCOP - Scott and White Hospital
Temple, Texas, 76508
Stormont-Vail Cancer Center
Topeka, Kansas, 66604
St. Francis Comprehensive Cancer Center
Topeka, Kansas, 66606
Munson Medical Center
Traverse City, Michigan, 49684
UVMC Cancer Care Center at Upper Valley Medical Center
Troy, Ohio, 45373
Legacy Meridian Park Hospital
Tualatin, Oregon, 97062
Southwest Washington Medical Center Cancer Center
Vancouver, Washington, 98668
Cancer Center of Kansas - Wellington
Wellington, Kansas, 67152
Central Washington Hospital
Wenatchee, Washington, 98801
Wenatchee Valley Clinic
Wenatchee, Washington, 98801
Mount Carmel Cancer Services at Mount Carmel St. Ann's Hospital
Westerville, Ohio, 43081
St. Anthony North Hospital
Westminster, Colorado, 80030
Exempla Lutheran Medical Center
Wheat Ridge, Colorado, 80033
Associates in Womens Health
Wichita, Kansas, 67203
Cancer Center of Kansas, P.A.
Wichita, Kansas, 67208
Cancer Center of Kansas, P.A. - Wichita
Wichita, Kansas, 67214
CCOP - Wichita
Wichita, Kansas, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, 67214
Wesley Medical Center
Wichita, Kansas, 67214
Cancer Center of Kansas - Winfield
Winfield, Kansas, 67156
Cleveland Clinic - Wooster
Wooster, Ohio, 44691
Ruth G. McMillan Cancer Center at Greene Memorial Hospital
Xenia, Ohio, 45385
Genesis - Good Samaritan Hospital
Zanesville, Ohio, 43701
About this study
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
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.
Read the 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.
- Being tested
- carmustine, radiation therapy, O6-Benzylguanine
- Keywords
- adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
- Medical subject headings
- Glioblastoma, Gliosarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
carmustineDrug
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 therapyRadiation
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.
O6-BenzylguanineDrug
Also called O6-BG
120 mg/m^2 IV over 1 hour on day 1 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| O6-BG + BCNU + Radiation Therapy | Experimental | O6-BG: 120 mg/m^2 IV over 1 hour on day 1 of each cycle BCNU: 40 mg/m^2 IV over 1 hour on day 1 of each cycle 6 hours after O6-BG dose. 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. Receives: Drug: carmustine; Radiation: radiation therapy; Drug: O6-Benzylguanine |
| BCNU + Radiation Therapy | Active comparator | BCNU: 40 mg/m^2 IV over 1 hour on day 1 of each cycle. 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. Receives: Drug: carmustine; Radiation: radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Measured: assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5
Secondary outcomes (3)
Progression-free survival
Measured: assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5
Time to treatment failure
Measured: assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5
Toxicity
Measured: assessed weekly for 42 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startSep 2001
- Primary completionMay 2006
- Study completionNov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous SystemStudies of the same condition, open and under way.
- More trials run by SWOG Cancer Research NetworkThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 183 participants (actual)
Sponsor and investigators
- Lead sponsor
- SWOG Cancer Research Network
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Deborah T. Blumenthal, MD, Study chair, University of UtahAlexander M. Spence, MD, Study chair, University of WashingtonKeith J. Stelzer, MD, PhD, Study chair, Celilo Cancer Center at Mid-Columbia Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00017147
- Sponsor's protocol ID
- CDR0000068656
- Other IDs
- S0001, U10CA032102
- Status last verified
- Jan 2013
- First submitted
- 6 Jun 2001
- Last updated
- 30 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 16033132Blumenthal DT, Rankin C, Stelzer KJ, Spence AM, Sloan AE, Moore DF Jr, Padula GD, Schulman SB, Wade ML, Rushing EJ. A Phase III study of radiation therapy (RT) and O(6)-benzylguanine + BCNU versus RT and BCNU alone and methylation status in newly diagnosed glioblastoma and gliosarcoma: Southwest Oncology Group (SWOG) study S0001. Int J Clin Oncol. 2015 Aug;20(4):650-8. doi: 10.1007/s10147-014-0769-0. Epub 2014 Nov 19.
PubMed 25407559
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00017147
- Acronym / sponsor ID
- CDR0000068656
- Keywords
- adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 183 participants (actual)
- Lead sponsor
- SWOG Cancer Research NetworkResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2001
- Primary completion
- May 2006 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 27 Jan 2003 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| O6-BG + BCNU + Radiation Therapy | Experimental | Drug: carmustine, Radiation: radiation therapy, Drug: O6-BenzylguanineO6-BG: 120 mg/m^2 IV over 1 hour on day 1 of each cycle BCNU: 40 mg/m^2 IV over 1 hour on day 1 of each cycle 6 hours after O6-BG dose. 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. |
| BCNU + Radiation Therapy | Active comparator | Drug: carmustine, Radiation: radiation therapyBCNU: 40 mg/m^2 IV over 1 hour on day 1 of each cycle. 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| carmustine40 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. | Drug | BCNU + Radiation Therapy, O6-BG + BCNU + Radiation Therapy |
| radiation therapy5 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. | Radiation | BCNU + Radiation Therapy, O6-BG + BCNU + Radiation Therapy |
| O6-BenzylguanineAlso: O6-BG120 mg/m^2 IV over 1 hour on day 1 of each cycle | Drug | O6-BG + BCNU + Radiation Therapy |
Primary outcome
Survival
Time frame: assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5
3 secondary outcomes
Progression-free survival
Time frame: assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5
Time to treatment failure
Time frame: assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5
Toxicity
Time frame: assessed weekly for 42 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2013.
- Results publicationBlumenthal 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.
- Results publication: PubMed 16033132Quezado 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.
- Derived from this study: PubMed 25407559Blumenthal DT, Rankin C, Stelzer KJ, Spence AM, Sloan AE, Moore DF Jr, Padula GD, Schulman SB, Wade ML, Rushing EJ. A Phase III study of radiation therapy (RT) and O(6)-benzylguanine + BCNU versus RT and BCNU alone and methylation status in newly diagnosed glioblastoma and gliosarcoma: Southwest Oncology Group (SWOG) study S0001. Int J Clin Oncol. 2015 Aug;20(4):650-8. doi: 10.1007/s10147-014-0769-0. Epub 2014 Nov 19.
Related trials for Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous System
Active, not recruitingPhase 2
Single Versus Multifraction Salvage Spine Stereotactic Radiosurgery for Previously Irradiated Spinal Metastases
Malignant Neoplasms of Eye Brain and Other Parts of Central Nervous System
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deborah T. Blumenthal, MD study chair
University of Utah
Alexander M. Spence, MD study chair
University of Washington
Keith J. Stelzer, MD, PhD study chair
Celilo Cancer Center at Mid-Columbia Medical Center
163 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing carmustine, radiation therapy and O6-Benzylguanine in people with Malignant Neoplasms of Eye, Brain and Other Parts of Central Nervous System, run by SWOG Cancer Research Network at 163 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 163 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival (time frame: assessed every 6 weeks for 42 weeks, then every 4 months for one year, followed by every 6 months for years 2 through 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00017147, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2013.