Brain and Central Nervous System TumorsPhase 3NCT00978458
Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma
A Phase 3 study testing temozolomide, 3-dimensional conformal radiation therapy and intensity-modulated radiation therapy in people with Brain and Central Nervous System Tumors and Neurotoxicity, run by Eastern Cooperative Oncology Group at 168 sites in United States.
Trial summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Brain and Central Nervous System Tumors, Neurotoxicity
- What is being tested?
- temozolomide, 3-dimensional conformal radiation therapy and intensity-modulated radiation therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 540 participants
- Where
- 168 sitesUnited States
- Study dates
- 17 Nov 2009to 31 Dec 2026
- Phase
- Phase 3
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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed* supratentorial low-grade glioma, including 1 of the following:
- Grade 2 astrocytoma
- Grade 2 oligodendroglioma
- Grade 2 oligoastrocytoma (mixed glioma containing astrocytoma and oligodendroglioma)
- NOTE: *If the pathology from multiple procedures supports the diagnosis of a brain tumor, the qualifying pathology of grade 2 astrocytoma, oligodendroglioma, or oligoastrocytoma must be the most recent pathological diagnosis; no pathological diagnosis of grade 3 or 4 glioma at any time
- Paraffin-embedded tumor specimen available for submission for confirmation of pathological review and determination of 1p and 19q deletion status
- Patients must currently meet ≥ 1 of the following criteria*:
- Uncontrolled symptoms, defined as any of the following:
- Headaches associated with mass effect
- Uncontrolled seizures despite two different antiepileptic drug regimens (i.e., two antiepileptic drugs tested either sequentially or in combination)
- Focal neurological symptoms
- Cognitive symptoms or deficits
- Tumor progression by serial MRIs, defined as any of the following:
- New or progressive enhancement
- New or progressive T2 or FLAIR signal abnormality
- Age ≥ 40 years
- NOTE: *Patients < 40 years of age whose only symptom of low-grade glioma is seizures that are well-controlled on antiepileptic drugs AND who have no evidence of radiographic progression are not eligible.
- Patients who have undergone gross total resection and have no detectable residual disease are eligible
- No pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, or dysembryoplastic neuroepithelial tumors
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100%
- WBC ≥ 3,000/mm^3
- ANC ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hematocrit ≥ 30%
- Bilirubin ≤ 2 times upper limit of normal (ULN)
- AST and ALT ≤ 3 times ULN
- Creatinine ≤ 2.0 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Able to undergo MRI with and without contrast
- No other malignancy within the past 5 years, except for nonmelanoma skin cancer or cervical carcinoma in situ
- No uncontrolled infection
- No known HIV positivity
- No medical disorder that would increase risks associated with radiotherapy and temozolomide
- No other disorder that would limit life expectancy to < 5 years
PRIOR CONCURRENT THERAPY:
- No prior radiotherapy, cytotoxic chemotherapy, radiosurgery, or investigational therapy directed at the brain tumor
- Any number of prior surgical procedures for the brain tumor allowed
- No prior radiotherapy to the head unless the radiotherapy ports entirely excluded the brain
- At least 2 weeks since any prior brain surgery (e.g., stereotatic biopsy, open biopsy, or resection)
- At least 6 weeks since prior MRI and chest x-ray
- If resection is performed, an MRI after surgery is required
Trial locations and contacts
168 sites in 1 country.
168 sites in 1 country
United States168 sites
Summa Center for Cancer Care at Akron City Hospital
Akron, Ohio, 44309-2090
New York Oncology Hematology, PC at Albany Medical Center
Albany, New York, 12208
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
Allentown, Pennsylvania, 18105
Theda Care Cancer Institute
Appleton, Wisconsin, 54911
Mission Hospitals - Memorial Campus
Asheville, North Carolina, 28801
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
Aurora Presbyterian Hospital
Aurora, Colorado, 80012
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231-2410
Barberton Citizens Hospital
Barberton, Ohio, 44203
St. Luke's Cancer Network at St. Luke's Hospital
Bethlehem, Pennsylvania, 18015
Billings Clinic - Downtown
Billings, Montana, 59107-7000
UAB Comprehensive Cancer Center
Birmingham, Alabama, 35294
Illinois CancerCare - Bloomington
Bloomington, Illinois, 61701
St. Joseph Medical Center
Bloomington, Illinois, 61701
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Graham Hospital
Canton, Illinois, 61520
Illinois CancerCare - Canton
Canton, Illinois, 61520
Illinois CancerCare - Carthage
Carthage, Illinois, 62321
Memorial Hospital
Carthage, Illinois, 62321
Hollings Cancer Center at Medical University of South Carolina
Charleston, South Carolina, 29425
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, 60611-3013
John H. Stroger, Jr. Hospital of Cook County
Chicago, Illinois, 60612-3785
University of Illinois Cancer Center
Chicago, Illinois, 60612-7243
University of Chicago Cancer Research Center
Chicago, Illinois, 60637-1470
Charles M. Barrett Cancer Center at University Hospital
Cincinnati, Ohio, 45267
Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, 44195
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210-1240
Mercy and Unity Cancer Center at Mercy Hospital
Coon Rapids, Minnesota, 55433
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
Dallas, Texas, 75390
Decatur Memorial Hospital Cancer Care Institute
Decatur, Illinois, 62526
St. Anthony Central Hospital
Denver, Colorado, 80204
Porter Adventist Hospital
Denver, Colorado, 80210
Presbyterian - St. Luke's Medical Center
Denver, Colorado, 80218
St. Joseph Hospital
Denver, Colorado, 80218
CCOP - Colorado Cancer Research Program
Denver, Colorado, 80222
CCOP - Iowa Oncology Research Association
Des Moines, Iowa, 50309
Josephine Ford Cancer Center at Henry Ford Hospital
Detroit, Michigan, 48202
CCOP - Duluth
Duluth, Minnesota, 55805
Marshfield Clinic Cancer Care at Regional Cancer Center
Eau Claire, Wisconsin, 54701
Fairview Southdale Hospital
Edina, Minnesota, 55435
Elkhart General Hospital
Elkhart, Indiana, 46515
Swedish Medical Center
Englewood, Colorado, 80110
Eureka Community Hospital
Eureka, Illinois, 61530
Illinois CancerCare - Eureka
Eureka, Illinois, 61530
Evanston Hospital
Evanston, Illinois, 60201-1781
Genesys Hurley Cancer Institute
Flint, Michigan, 48503
Hurley Medical Center
Flint, Michigan, 48503
Radiation Oncology Associates Southwest
Fort Wayne, Indiana, 46804
Parkview Regional Cancer Center at Parkview Health
Fort Wayne, Indiana, 46805
Mercy and Unity Cancer Center at Unity Hospital
Fridley, Minnesota, 55432
Galesburg Clinic, PC
Galesburg, Illinois, 61401
University of Texas Medical Branch
Galveston, Texas, 77555-0361
St. Vincent Hospital Regional Cancer Center
Green Bay, Wisconsin, 54307-3508
Cancer Centers of the Carolinas - Faris Road
Greenville, South Carolina, 29605
Cancer Centers of the Carolinas - Grove Commons
Greenville, South Carolina, 29605
Cancer Centers of the Carolinas - Eastside
Greenville, South Carolina, 29615
CCOP - Greenville
Greenville, South Carolina, 29615
Cancer Centers of the Carolinas - Greer Medical Oncology
Greer, South Carolina, 29650
Cancer Centers of the Carolinas - Greer Radiation Oncology
Greer, South Carolina, 29650
Legacy Mount Hood Medical Center
Gresham, Oregon, 97030
Illinois CancerCare - Havana
Havana, Illinois, 62644
M. D. Anderson Cancer Center at University of Texas
Houston, Texas, 77030-4009
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350
Community Regional Cancer Care at Community Hospital East
Indianapolis, Indiana, 46219
Community Regional Cancer Care at Community Hospital North
Indianapolis, Indiana, 46256
Mayo Clinic - Jacksonville
Jacksonville, Florida, 32224
West Michigan Cancer Center
Kalamazoo, Michigan, 49007-3731
Illinois CancerCare - Kewanee Clinic
Kewanee, Illinois, 61443
Howard Community Hospital
Kokomo, Indiana, 46904
Gundersen Lutheran Center for Cancer and Blood
La Crosse, Wisconsin, 54601
La Grange Memorial Hospital
La Grange, Illinois, 60525
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, 92093-0658
Center for Cancer Therapy at LaPorte Hospital and Health Services
La Porte, Indiana, 46350
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756-0002
Cancer Resource Center - Lincoln
Lincoln, Nebraska, 68510
Sky Ridge Medical Center
Lone Tree, Colorado, 80124
Louisville Oncology at Norton Cancer Institute - Louisville
Louisville, Kentucky, 40202
Norton Suburban Hospital
Louisville, Kentucky, 40207
Illinois CancerCare - Macomb
Macomb, Illinois, 61455
McDonough District Hospital
Macomb, Illinois, 61455
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, Wisconsin, 53792-6164
HealthEast Cancer Care at St. John's Hospital
Maplewood, Minnesota, 55109
Minnesota Oncology - Maplewood
Maplewood, Minnesota, 55109
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, 54449
Saint Joseph's Hospital
Marshfield, Wisconsin, 54449
Mercy Cancer Center at Mercy Medical Center - North Iowa
Mason City, Iowa, 50401
Columbia Saint Mary's Hospital - Ozaukee
Mequon, Wisconsin, 53097
Columbia-Saint Mary's Cancer Care Center
Milwaukee, Wisconsin, 53211
Medical College of Wisconsin Cancer Center
Milwaukee, Wisconsin, 53226
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
Minneapolis, Minnesota, 55407
Hennepin County Medical Center - Minneapolis
Minneapolis, Minnesota, 55415
Marshfield Clinic - Lakeland Center
Minocqua, Wisconsin, 54548
Michiana Hematology-Oncology, PC - South Bend
Mishawaka, Indiana, 46545-1470
Illinois CancerCare - Monmouth
Monmouth, Illinois, 61462
OSF Holy Family Medical Center
Monmouth, Illinois, 61462
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
Murray, Utah, 84157
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
CCOP - Christiana Care Health Services
Newark, Delaware, 19713
BroMenn Regional Medical Center
Normal, Illinois, 61761
Community Cancer Center
Normal, Illinois, 61761
Illinois CancerCare - Community Cancer Center
Normal, Illinois, 61761
Eastern Connecticut Hematology and Oncology Associates
Norwich, Connecticut, 06360
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, 68106
Methodist Estabrook Cancer Center
Omaha, Nebraska, 68114
Nebraska Medical Center
Omaha, Nebraska, 68198
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
Orange, California, 92868
Florida Hospital Cancer Institute at Florida Hospital Orlando
Orlando, Florida, 32803-1273
Community Hospital of Ottawa
Ottawa, Illinois, 61350
Oncology Hematology Associates of Central Illinois, PC - Ottawa
Ottawa, Illinois, 61350
Cancer Treatment Center at Pekin Hospital
Pekin, Illinois, 61554
Illinois CancerCare - Pekin
Pekin, Illinois, 61603
Proctor Hospital
Peoria, Illinois, 61614
OSF St. Francis Medical Center
Peoria, Illinois, 61615-7827
CCOP - Illinois Oncology Research Association
Peoria, Illinois, 61615
Oncology Hematology Associates of Central Illinois, PC - Peoria
Peoria, Illinois, 61615
Methodist Medical Center of Illinois
Peoria, Illinois, 61636
Illinois CancerCare - Peru
Peru, Illinois, 61354
Illinois Valley Community Hospital
Peru, Illinois, 61354
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
Philadelphia, Pennsylvania, 19107-5541
Arizona Oncology Services Foundation
Phoenix, Arizona, 85013
Legacy Good Samaritan Hospital & Comprehensive Cancer Center
Portland, Oregon, 97210
Illinois CancerCare - Princeton
Princeton, Illinois, 61356
Utah Valley Regional Medical Center - Provo
Provo, Utah, 84604
Rapid City Regional Hospital
Rapid City, South Dakota, 57701
Ministry Medical Group at Saint Mary's Hospital
Rhinelander, Wisconsin, 54501
Marshfield Clinic - Indianhead Center
Rice Lake, Wisconsin, 54868
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, 23298-0037
Humphrey Cancer Center at North Memorial Outpatient Center
Robbinsdale, Minnesota, 55422-2900
Mayo Clinic Cancer Center
Rochester, Minnesota, 55905
Lakeland Regional Cancer Care Center - St. Joseph
Saint Joseph, Michigan, 49085
Lakeside Cancer Specialists, PLLC
Saint Joseph, Michigan, 49085
CCOP - Metro-Minnesota
Saint Louis Park, Minnesota, 55416
Park Nicollet Cancer Center
Saint Louis Park, Minnesota, 55416
Regions Hospital Cancer Care Center
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Maine Center for Cancer Medicine and Blood Disorders - Scarborough
Scarborough, Maine, 04074
CCOP - Virginia Mason Research Center
Seattle, Washington, 98101
University Cancer Center at University of Washington Medical Center
Seattle, Washington, 98195
Cancer Centers of the Carolinas - Seneca
Seneca, South Carolina, 29672
St. Francis Cancer Center at St. Francis Medical Center
Shakopee, Minnesota, 55379
Siouxland Hematology-Oncology Associates, LLP
Sioux City, Iowa, 51101
Sanford Cancer Center at Sanford USD Medical Center
Sioux Falls, South Dakota, 57117-5039
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, 46601
Memorial Hospital of South Bend
South Bend, Indiana, 46601
CCOP - Upstate Carolina
Spartanburg, South Carolina, 29303
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
Spartanburg, South Carolina, 29303
Cancer Centers of the Carolinas - Spartanburg
Spartanburg, South Carolina, 29307
Illinois CancerCare - Spring Valley
Spring Valley, Illinois, 61362
Valley Cancer Center
Spring Valley, Illinois, 61362
Dixie Regional Medical Center - East Campus
St. George, Utah, 84770
Marshfield Clinic at Saint Michael's Hospital
Stevens Point, Wisconsin, 54481
Lakeview Hospital
Stillwater, Minnesota, 55082
SUNY Upstate Medical University Hospital
Syracuse, New York, 13210
Legacy Salmon Creek Medical Center
Vancouver, Washington, 98686
Ridgeview Medical Center
Waconia, Minnesota, 55387
Waukesha Memorial Hospital Regional Cancer Center
Waukesha, Wisconsin, 53188
Cancer Center of Kansas, PA - Wellington
Wellington, Kansas, 67152
Diagnostic and Treatment Center
Weston, Wisconsin, 54476
Marshfield Clinic - Weston Center
Weston, Wisconsin, 54476
Cancer Center of Kansas, PA - Wichita
Wichita, Kansas, 67214
CCOP - Wichita
Wichita, Kansas, 67214
Via Christi Cancer Center at Via Christi Regional Medical Center
Wichita, Kansas, 67214
Willmar Cancer Center at Rice Memorial Hospital
Willmar, Minnesota, 56201
Cancer Center of Kansas, PA - Winfield
Winfield, Kansas, 67156
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157-1096
Minnesota Oncology - Woodbury
Woodbury, Minnesota, 55125
About this study
Official title: Phase III Study of Radiation Therapy With or Without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether radiation therapy is more effective when given together with or without temozolomide in treating patients with low-grade glioma.
PURPOSE: This randomized phase III trial is studying radiation therapy so see how well it works when given together with or without temozolomide in treating patients with low-grade glioma.
Read the detailed description
OBJECTIVES:
Primary
- To determine whether the addition of temozolomide to fractionated radiotherapy improves the progression-free survival (PFS) of patients with symptomatic or progressive low-grade gliomas.
- To determine whether the addition of temozolomide to fractionated radiotherapy improves the median overall survival (OS) of these patients.
Secondary
- To determine whether combination therapy with temozolomide and radiotherapy improves or maintains cognition and quality of life compared to radiotherapy alone.
- To compare the toxicities (severe or worse [≥ grade 3]) of radiotherapy with vs without temozolomide in these patients.
- To assess the impact of the presence or absence of 1p and 19q deletion on PFS and OS.
- To determine the impact of 1p and 19q status on PFS and OS of patients treated with temozolomide.
- To create a tumor and tissue bank, including plasma and germ line DNA, within the ECOG Pathology Coordinating Office.
OUTLINE: This is a multicenter study. Patients are stratified according to age (< 40 years vs ≥ 40 years), 1p and 19q status (both deleted vs either/both intact vs undeterminable), pre-operative maximum tumor diameter (< 6 cm vs ≥ 6 cm [based on T2 or FLAIR MRI]), Karnofsky performance status (60-70% vs 80-100%), and contrast enhancement on pre-treatment MRI scan (present vs absent). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).
- Arm II: Patients undergo radiotherapy as in arm I and receive concurrent oral temozolomide once daily for 5½ weeks. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
Some patients undergo quality-of-life and neurocognitive (e.g., visual scanning speed, divided attention, language, memory, and fine motor skills) assessments at baseline, annually until disease progression, and at the time of disease progression.
Tumor tissue samples are collected at baseline for confirmation of diagnosis and determination of 1p and 19q deletion status. Peripheral blood, serum, and additional tumor tissue samples may be collected for further research studies.
After completion of study treatment, patients are followed up periodically for up to 15 years.
- Being tested
- temozolomide, 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy
- Keywords
- neurotoxicity, adult diffuse astrocytoma, adult oligodendroglioma, recurrent adult brain tumor, adult mixed glioma
- Medical subject headings
- Central Nervous System Neoplasms, Neurotoxicity Syndromes, Astrocytoma, Oligodendroglioma, Brain Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
temozolomideDrug
Given orally
3-dimensional conformal radiation therapyRadiation
Given once daily 5 days a week for 5½ weeks
intensity-modulated radiation therapyRadiation
Given once daily 5 days a week for 5½ weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Active comparator | Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions). Receives: Radiation: 3-dimensional conformal radiation therapy; Radiation: intensity-modulated radiation therapy |
| Arm II | Experimental | Patients undergo radiotherapy as in arm I and receive concurrent oral temozolomide once daily for 5½ weeks. Beginning 28 days after completion of chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: temozolomide; Radiation: 3-dimensional conformal radiation therapy; Radiation: intensity-modulated radiation therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
Overall survival (OS)
Secondary outcomes (3)
Quality of life as assessed by the FACT-BR questionnaire at baseline, annually until disease progression, and at the time of disease progression
Neurocognitive functioning as assessed at baseline, annually until disease progression, and at the time of disease progression
Correlation of pre-treatment 1p and 19q levels in tumor tissue samples with PFS and OS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2009 (estimated)
- Study start17 Nov 2009
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Brain and Central Nervous System TumorsStudies of the same condition, open and under way.
- 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
- Enrolment
- 540 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eastern Cooperative Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- David Schiff, MD, Study chair, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00978458
- Sponsor's protocol ID
- E3F05
- Other IDs
- ECOG-E3F05
- Status last verified
- Oct 2026
- First submitted
- 16 Sep 2009
- Last updated
- 5 Oct 2026
- Results posted
- No