Know Cancer

forgot password

Phase III Study of Radiation Therapy With or Without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas

Phase 3
18 Years
Open (Enrolling)
Brain and Central Nervous System Tumors, Neurotoxicity

Thank you

Trial Information

Phase III Study of Radiation Therapy With or Without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas



- 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.


- 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

- 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

Inclusion Criteria


- Histologically confirmed* supratentorial low-grade glioma, including 1 of the

- Grade 2 astrocytoma

- Grade 2 oligodendroglioma

- Grade 2 oligoastrocytoma (mixed glioma containing astrocytoma and

- 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

- 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


- 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

- No other disorder that would limit life expectancy to < 5 years


- 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

- 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

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Safety Issue:


Principal Investigator

David Schiff, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Virginia



Study ID:




Start Date:

September 2009

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Neurotoxicity
  • neurotoxicity
  • adult diffuse astrocytoma
  • adult oligodendroglioma
  • recurrent adult brain tumor
  • adult mixed glioma
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Neurotoxicity Syndromes



Memorial Sloan-Kettering Cancer Center New York, New York  10021
Mayo Clinic - Jacksonville Jacksonville, Florida  32224
Mayo Clinic Cancer Center Rochester, Minnesota  55905
University of Chicago Cancer Research Center Chicago, Illinois  60637
CCOP - Upstate Carolina Spartanburg, South Carolina  29303
CCOP - Wichita Wichita, Kansas  67214-3882
Hurley Medical Center Flint, Michigan  48503
CCOP - Missouri Valley Cancer Consortium Omaha, Nebraska  68131
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
CCOP - Illinois Oncology Research Association Peoria, Illinois  61602
CCOP - Iowa Oncology Research Association Des Moines, Iowa  50309-1016
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
Aurora Presbyterian Hospital Aurora, Colorado  80012
CCOP - Colorado Cancer Research Program Denver, Colorado  80224-2522
Porter Adventist Hospital Denver, Colorado  80210
Presbyterian - St. Luke's Medical Center Denver, Colorado  80218
St. Joseph Hospital Denver, Colorado  80218
Swedish Medical Center Englewood, Colorado  80110
Sky Ridge Medical Center Lone Tree, Colorado  80124
Siouxland Hematology-Oncology Associates, LLP Sioux City, Iowa  51101
Genesys Hurley Cancer Institute Flint, Michigan  48503
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
Fairview Ridges Hospital Burnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids, Minnesota  55433
CCOP - Duluth Duluth, Minnesota  55805
Fairview Southdale Hospital Edina, Minnesota  55435
Mercy and Unity Cancer Center at Unity Hospital Fridley, Minnesota  55432
Hutchinson Area Health Care Hutchinson, Minnesota  55350
HealthEast Cancer Care at St. John's Hospital Maplewood, Minnesota  55109
Hennepin County Medical Center - Minneapolis Minneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital Minneapolis, Minnesota  55407
St. Francis Cancer Center at St. Francis Medical Center Shakopee, Minnesota  55379
Park Nicollet Cancer Center St. Louis Park, Minnesota  55416
Regions Hospital Cancer Care Center St. Paul, Minnesota  55101
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Case Comprehensive Cancer Center Cleveland, Ohio  44106-5065
Sanford Cancer Center at Sanford USD Medical Center Sioux Falls, South Dakota  57117-5039
Vanderbilt-Ingram Cancer Center Nashville, Tennessee  37232-6838
University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Madison, Wisconsin  53792-6164
Marshfield Clinic - Marshfield Center Marshfield, Wisconsin  54449
Medical College of Wisconsin Cancer Center Milwaukee, Wisconsin  53226
Marshfield Clinic - Indianhead Center Rice Lake, Wisconsin  54868
Rapid City Regional Hospital Rapid City, South Dakota  57709
Methodist Medical Center of Illinois Peoria, Illinois  61636
Memorial Hospital of South Bend South Bend, Indiana  46601
CCOP - Greenville Greenville, South Carolina  29615
University of Texas Medical Branch Galveston, Texas  77555-1329
CCOP - Northern Indiana CR Consortium South Bend, Indiana  46601
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center Lebanon, New Hampshire  03756-0002
Charles M. Barrett Cancer Center at University Hospital Cincinnati, Ohio  45267-0526
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia Philadelphia, Pennsylvania  19107
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland  21231-2410
Cleveland Clinic Taussig Cancer Center Cleveland, Ohio  44195
CCOP - Virginia Mason Research Center Seattle, Washington  98101
Utah Valley Regional Medical Center - Provo Provo, Utah  84604
Rebecca and John Moores UCSD Cancer Center La Jolla, California  92093-0658
Josephine Ford Cancer Center at Henry Ford Hospital Detroit, Michigan  48202
Maine Center for Cancer Medicine and Blood Disorders - Scarborough Scarborough, Maine  04074
Waukesha Memorial Hospital Regional Cancer Center Waukesha, Wisconsin  53188
Florida Hospital Cancer Institute at Florida Hospital Orlando Orlando, Florida  32803-1273
Winship Cancer Institute of Emory University Atlanta, Georgia  30322
Via Christi Cancer Center at Via Christi Regional Medical Center Wichita, Kansas  67214
SUNY Upstate Medical University Hospital Syracuse, New York  13210
Mission Hospitals - Memorial Campus Asheville, North Carolina  28801
Wake Forest University Comprehensive Cancer Center Winston-Salem, North Carolina  27157-1096
Hollings Cancer Center at Medical University of South Carolina Charleston, South Carolina  29425
Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas Dallas, Texas  75390
St. Vincent Hospital Regional Cancer Center Green Bay, Wisconsin  54307-3508
University Cancer Center at University of Washington Medical Center Seattle, Washington  98195
University of Illinois Cancer Center Chicago, Illinois  60612-7243
M. D. Anderson Cancer Center at University of Texas Houston, Texas  77030-4009
Virginia Commonwealth University Massey Cancer Center Richmond, Virginia  23298-0037
Gundersen Lutheran Center for Cancer and Blood La Crosse, Wisconsin  54601
Methodist Estabrook Cancer Center Omaha, Nebraska  68114-4199
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center Orange, California  92868
Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago, Illinois  60611
Decatur Memorial Hospital Cancer Care Institute Decatur, Illinois  62526
Elkhart General Hospital Elkhart, Indiana  46515
Howard Community Hospital Kokomo, Indiana  46904
Lakeland Regional Cancer Care Center - St. Joseph St. Joseph, Michigan  49085
Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest Allentown, Pennsylvania  18105
St. Joseph Medical Center Bloomington, Illinois  61701
Graham Hospital Canton, Illinois  61520
Memorial Hospital Carthage, Illinois  62321
Eureka Community Hospital Eureka, Illinois  61530
McDonough District Hospital Macomb, Illinois  61455
BroMenn Regional Medical Center Normal, Illinois  61761
Community Cancer Center Normal, Illinois  61761
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
Oncology Hematology Associates of Central Illinois, PC - Peoria Peoria, Illinois  61615
OSF St. Francis Medical Center Peoria, Illinois  61637
Proctor Hospital Peoria, Illinois  61614
Illinois Valley Community Hospital Peru, Illinois  61354
Valley Cancer Center Spring Valley, Illinois  61362
Center for Cancer Therapy at LaPorte Hospital and Health Services La Porte, Indiana  46350
Legacy Mount Hood Medical Center Gresham, Oregon  97030
Dixie Regional Medical Center - East Campus Saint George, Utah  84770
St. Anthony Central Hospital Denver, Colorado  80204-1335
Mercy Cancer Center at Mercy Medical Center - North Iowa Mason City, Iowa  50401
Cancer Resource Center - Lincoln Lincoln, Nebraska  68510
UAB Comprehensive Cancer Center Birmingham, Alabama  35294
Eastern Connecticut Hematology and Oncology Associates Norwich, Connecticut  06360
Evanston Hospital Evanston, Illinois  60201-1781
Michiana Hematology-Oncology, PC - South Bend Mishawaka, Indiana  46545-1470
Cancer Center of Kansas, PA - Wellington Wellington, Kansas  67152
Cancer Center of Kansas, PA - Wichita Wichita, Kansas  67214
Cancer Center of Kansas, PA - Winfield Winfield, Kansas  67156
Lakeside Cancer Specialists, PLLC Saint Joseph, Michigan  49085
Willmar Cancer Center at Rice Memorial Hospital Willmar, Minnesota  56201
Billings Clinic - Downtown Billings, Montana  59107-7000
Summa Center for Cancer Care at Akron City Hospital Akron, Ohio  44309-2090
Barberton Citizens Hospital Barberton, Ohio  44203
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus, Ohio  43210-1240
Legacy Good Samaritan Hospital & Comprehensive Cancer Center Portland, Oregon  97210
St. Luke's Cancer Network at St. Luke's Hospital Bethlehem, Pennsylvania  18015
Jon and Karen Huntsman Cancer Center at Intermountain Medical Center Murray, Utah  84157
Legacy Salmon Creek Medical Center Vancouver, Washington  98686
Marshfield Clinic Cancer Care at Regional Cancer Center Eau Claire, Wisconsin  54701
Saint Joseph's Hospital Marshfield, Wisconsin  54449
Marshfield Clinic - Lakeland Center Minocqua, Wisconsin  54548
Ministry Medical Group at Saint Mary's Hospital Rhinelander, Wisconsin  54501
Marshfield Clinic at Saint Michael's Hospital Stevens Point, Wisconsin  54481
Marshfield Clinic - Weston Center Weston, Wisconsin  54476
Diagnostic and Treatment Center Weston, Wisconsin  54476
John H. Stroger, Jr. Hospital of Cook County Chicago, Illinois  60612-9985
Arizona Oncology Services Foundation Phoenix, Arizona  85013
Parkview Regional Cancer Center at Parkview Health Fort Wayne, Indiana  46805
Gibbs Regional Cancer Center at Spartanburg Regional Medical Center Spartanburg, South Carolina  29303
Theda Care Cancer Institute Appleton, Wisconsin  54911
Cancer Centers of the Carolinas - Grove Commons Greenville, South Carolina  29605
Cancer Centers of the Carolinas - Faris Road Greenville, South Carolina  29605
Cancer Centers of the Carolinas - Greer Medical Oncology Greer, South Carolina  29650
Cancer Centers of the Carolinas - Seneca Seneca, South Carolina  29672
Cancer Centers of the Carolinas - Spartanburg Spartanburg, South Carolina  29307
Cancer Centers of the Carolinas - Eastside Greenville, South Carolina  29601
La Grange Memorial Hospital La Grange, Illinois  60525
Louisville Oncology at Norton Cancer Institute - Louisville Louisville, Kentucky  40202
Galesburg Clinic, PC Galesburg, Illinois  61401
Illinois CancerCare - Bloomington Bloomington%, Illinois  61701
Illinois CancerCare - Canton Canton, Illinois  61520
Illinois CancerCare - Carthage Carthage, Illinois  62321
Illinois CancerCare - Eureka Eureka, Illinois  61530
Illinois CancerCare - Havana Havana, Illinois  62644
Illinois CancerCare - Kewanee Clinic Kewanee, Illinois  61443
Illinois CancerCare - Macomb Macomb, Illinois  61455
OSF Holy Family Medical Center Monmouth, Illinois  61462
Illinois CancerCare - Monmouth Monmouth, Illinois  61462
Illinois CancerCare - Community Cancer Center Normal, Illinois  61761
Illinois CancerCare - Pekin Pekin, Illinois  61603
Illinois CancerCare - Peru Peru, Illinois  61354
Illinois CancerCare - Princeton Princeton, Illinois  61356
Illinois CancerCare - Spring Valley Spring Valley, Illinois  61362
Columbia Saint Mary's Hospital - Ozaukee Mequon, Wisconsin  53097
Columbia-Saint Mary's Cancer Care Center Milwaukee, Wisconsin  53211
Cancer Centers of the Carolinas - Greer Radiation Oncology Greer, South Carolina  29650
Minnesota Oncology - Maplewood Maplewood, Minnesota  55109
Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale, Minnesota  55422-2900
Lakeview Hospital Stillwater, Minnesota  55082
Minnesota Oncology - Woodbury Woodbury, Minnesota  55125
New York Oncology Hematology, PC at Albany Medical Center Albany, New York  12208
Community Regional Cancer Care at Community Hospital North Indianapolis, Indiana  46256
Community Regional Cancer Care at Community Hospital East Indianapolis, Indiana  46219
Radiation Oncology Associates Southwest Fort Wayne, Indiana  46804
Nebraska Medical Center Omaha, Nebraska  68198
Norton Suburban Hospital Louisville, Kentucky  40207