Clinical trial NCT00978458: Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma
Official title: Phase III Study of Radiation Therapy With or Without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Brain and Central Nervous System Tumors
Neurotoxicity
Keywords: neurotoxicity
adult diffuse astrocytoma
adult oligodendroglioma
recurrent adult brain tumor
adult mixed glioma
Lead sponsor: Eastern Cooperative Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-09-17
Enrollment: 540
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression-free survival (PFS)
measure: Overall survival (OS)
Secondary outcomes:
measure: Quality of life as assessed by the FACT-BR questionnaire at baseline, annually until disease progression, and at the time of disease progression
measure: Neurocognitive functioning as assessed at baseline, annually until disease progression, and at the time of disease progression
measure: Correlation of pre-treatment 1p and 19q levels in tumor tissue samples with PFS and OS
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB Comprehensive Cancer Center
state: Alabama
city: Phoenix
country: United States
facility: Arizona Oncology Services Foundation
state: Arizona
city: La Jolla
country: United States
facility: Rebecca and John Moores UCSD Cancer Center
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
state: California
city: Aurora
country: United States
facility: Aurora Presbyterian Hospital
state: Colorado
city: Denver
country: United States
facility: St. Anthony Central Hospital
state: Colorado
city: Denver
country: United States
facility: Porter Adventist Hospital
state: Colorado
city: Denver
country: United States
facility: Presbyterian - St. Luke's Medical Center
state: Colorado
city: Denver
country: United States
facility: St. Joseph Hospital
state: Colorado
city: Denver
country: United States
facility: CCOP - Colorado Cancer Research Program
state: Colorado
city: Englewood
country: United States
facility: Swedish Medical Center
state: Colorado
city: Lone Tree
country: United States
facility: Sky Ridge Medical Center
state: Colorado
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Newark
country: United States
facility: CCOP - Christiana Care Health Services
state: Delaware
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Orlando
country: United States
facility: Florida Hospital Cancer Institute at Florida Hospital Orlando
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Bloomington
country: United States
facility: Illinois CancerCare - Bloomington
state: Illinois
city: Bloomington
country: United States
facility: St. Joseph Medical Center
state: Illinois
city: Canton
country: United States
facility: Graham Hospital
state: Illinois
city: Canton
country: United States
facility: Illinois CancerCare - Canton
state: Illinois
city: Carthage
country: United States
facility: Illinois CancerCare - Carthage
state: Illinois
city: Carthage
country: United States
facility: Memorial Hospital
state: Illinois
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
city: Chicago
country: United States
facility: John H. Stroger, Jr. Hospital of Cook County
state: Illinois
city: Chicago
country: United States
facility: University of Illinois Cancer Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Cancer Research Center
state: Illinois
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Eureka
country: United States
facility: Eureka Community Hospital
state: Illinois
city: Eureka
country: United States
facility: Illinois CancerCare - Eureka
state: Illinois
city: Evanston
country: United States
facility: Evanston Hospital
state: Illinois
city: Galesburg
country: United States
facility: Galesburg Clinic, PC
state: Illinois
city: Havana
country: United States
facility: Illinois CancerCare - Havana
state: Illinois
city: Kewanee
country: United States
facility: Illinois CancerCare - Kewanee Clinic
state: Illinois
city: La Grange
country: United States
facility: La Grange Memorial Hospital
state: Illinois
city: Macomb
country: United States
facility: Illinois CancerCare - Macomb
state: Illinois
city: Macomb
country: United States
facility: McDonough District Hospital
state: Illinois
city: Monmouth
country: United States
facility: Illinois CancerCare - Monmouth
state: Illinois
city: Monmouth
country: United States
facility: OSF Holy Family Medical Center
state: Illinois
city: Normal
country: United States
facility: BroMenn Regional Medical Center
state: Illinois
city: Normal
country: United States
facility: Community Cancer Center
state: Illinois
city: Normal
country: United States
facility: Illinois CancerCare - Community Cancer Center
state: Illinois
city: Ottawa
country: United States
facility: Community Hospital of Ottawa
state: Illinois
city: Ottawa
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Ottawa
state: Illinois
city: Pekin
country: United States
facility: Cancer Treatment Center at Pekin Hospital
state: Illinois
city: Pekin
country: United States
facility: Illinois CancerCare - Pekin
state: Illinois
city: Peoria
country: United States
facility: Proctor Hospital
state: Illinois
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Peoria
country: United States
facility: CCOP - Illinois Oncology Research Association
state: Illinois
city: Peoria
country: United States
facility: Oncology Hematology Associates of Central Illinois, PC - Peoria
state: Illinois
city: Peoria
country: United States
facility: Methodist Medical Center of Illinois
state: Illinois
city: Peru
country: United States
facility: Illinois CancerCare - Peru
state: Illinois
city: Peru
country: United States
facility: Illinois Valley Community Hospital
state: Illinois
city: Princeton
country: United States
facility: Illinois CancerCare - Princeton
state: Illinois
city: Spring Valley
country: United States
facility: Illinois CancerCare - Spring Valley
state: Illinois
city: Spring Valley
country: United States
facility: Valley Cancer Center
state: Illinois
city: Elkhart
country: United States
facility: Elkhart General Hospital
state: Indiana
city: Fort Wayne
country: United States
facility: Radiation Oncology Associates Southwest
state: Indiana
city: Fort Wayne
country: United States
facility: Parkview Regional Cancer Center at Parkview Health
state: Indiana
city: Indianapolis
country: United States
facility: Community Regional Cancer Care at Community Hospital East
state: Indiana
city: Indianapolis
country: United States
facility: Community Regional Cancer Care at Community Hospital North
state: Indiana
city: Kokomo
country: United States
facility: Howard Community Hospital
state: Indiana
city: La Porte
country: United States
facility: Center for Cancer Therapy at LaPorte Hospital and Health Services
state: Indiana
city: Mishawaka
country: United States
facility: Michiana Hematology-Oncology, PC - South Bend
state: Indiana
city: South Bend
country: United States
facility: CCOP - Northern Indiana CR Consortium
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital of South Bend
state: Indiana
city: Des Moines
country: United States
facility: CCOP - Iowa Oncology Research Association
state: Iowa
city: Mason City
country: United States
facility: Mercy Cancer Center at Mercy Medical Center - North Iowa
state: Iowa
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology Associates, LLP
state: Iowa
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Louisville
country: United States
facility: Louisville Oncology at Norton Cancer Institute - Louisville
state: Kentucky
city: Louisville
country: United States
facility: Norton Suburban Hospital
state: Kentucky
city: Scarborough
country: United States
facility: Maine Center for Cancer Medicine and Blood Disorders - Scarborough
state: Maine
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Detroit
country: United States
facility: Josephine Ford Cancer Center at Henry Ford Hospital
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Kalamazoo
country: United States
facility: West Michigan Cancer Center
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeland Regional Cancer Care Center - St. Joseph
state: Michigan
city: Saint Joseph
country: United States
facility: Lakeside Cancer Specialists, PLLC
state: Michigan
city: Burnsville
country: United States
facility: Fairview Ridges Hospital
state: Minnesota
city: Coon Rapids
country: United States
facility: Mercy and Unity Cancer Center at Mercy Hospital
state: Minnesota
city: Duluth
country: United States
facility: CCOP - Duluth
state: Minnesota
city: Edina
country: United States
facility: Fairview Southdale Hospital
state: Minnesota
city: Fridley
country: United States
facility: Mercy and Unity Cancer Center at Unity Hospital
state: Minnesota
city: Hutchinson
country: United States
facility: Hutchinson Area Health Care
state: Minnesota
city: Maplewood
country: United States
facility: HealthEast Cancer Care at St. John's Hospital
state: Minnesota
city: Maplewood
country: United States
facility: Minnesota Oncology - Maplewood
state: Minnesota
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute at Abbott - Northwestern Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Hennepin County Medical Center - Minneapolis
state: Minnesota
city: Robbinsdale
country: United States
facility: Humphrey Cancer Center at North Memorial Outpatient Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Saint Louis Park
country: United States
facility: CCOP - Metro-Minnesota
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Cancer Center
state: Minnesota
city: Saint Paul
country: United States
facility: Regions Hospital Cancer Care Center
state: Minnesota
city: Saint Paul
country: United States
facility: United Hospital
state: Minnesota
city: Shakopee
country: United States
facility: St. Francis Cancer Center at St. Francis Medical Center
state: Minnesota
city: Stillwater
country: United States
facility: Lakeview Hospital
state: Minnesota
city: Waconia
country: United States
facility: Ridgeview Medical Center
state: Minnesota
city: Willmar
country: United States
facility: Willmar Cancer Center at Rice Memorial Hospital
state: Minnesota
city: Woodbury
country: United States
facility: Minnesota Oncology - Woodbury
state: Minnesota
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Lincoln
country: United States
facility: Cancer Resource Center - Lincoln
state: Nebraska
city: Omaha
country: United States
facility: CCOP - Missouri Valley Cancer Consortium
state: Nebraska
city: Omaha
country: United States
facility: Methodist Estabrook Cancer Center
state: Nebraska
city: Omaha
country: United States
facility: Nebraska Medical Center
state: Nebraska
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Albany
country: United States
facility: New York Oncology Hematology, PC at Albany Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University Hospital
state: New York
city: Asheville
country: United States
facility: Mission Hospitals - Memorial Campus
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest University Comprehensive Cancer Center
state: North Carolina
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Barberton
country: United States
facility: Barberton Citizens Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
state: Ohio
city: Gresham
country: United States
facility: Legacy Mount Hood Medical Center
state: Oregon
city: Portland
country: United States
facility: Legacy Good Samaritan Hospital & Comprehensive Cancer Center
state: Oregon
city: Allentown
country: United States
facility: Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
state: Pennsylvania
city: Bethlehem
country: United States
facility: St. Luke's Cancer Network at St. Luke's Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center at Thomas Jefferson University - Philadelphia
state: Pennsylvania
city: Charleston
country: United States
facility: Hollings Cancer Center at Medical University of South Carolina
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Faris Road
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Grove Commons
state: South Carolina
city: Greenville
country: United States
facility: Cancer Centers of the Carolinas - Eastside
state: South Carolina
city: Greenville
country: United States
facility: CCOP - Greenville
state: South Carolina
city: Greer
country: United States
facility: Cancer Centers of the Carolinas - Greer Medical Oncology
state: South Carolina
city: Greer
country: United States
facility: Cancer Centers of the Carolinas - Greer Radiation Oncology
state: South Carolina
city: Seneca
country: United States
facility: Cancer Centers of the Carolinas - Seneca
state: South Carolina
city: Spartanburg
country: United States
facility: CCOP - Upstate Carolina
state: South Carolina
city: Spartanburg
country: United States
facility: Gibbs Regional Cancer Center at Spartanburg Regional Medical Center
state: South Carolina
city: Spartanburg
country: United States
facility: Cancer Centers of the Carolinas - Spartanburg
state: South Carolina
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Sioux Falls
country: United States
facility: Sanford Cancer Center at Sanford USD Medical Center
state: South Dakota
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Murray
country: United States
facility: Jon and Karen Huntsman Cancer Center at Intermountain Medical Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center - East Campus
state: Utah
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Seattle
country: United States
facility: CCOP - Virginia Mason Research Center
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Vancouver
country: United States
facility: Legacy Salmon Creek Medical Center
state: Washington
city: Appleton
country: United States
facility: Theda Care Cancer Institute
state: Wisconsin
city: Eau Claire
country: United States
facility: Marshfield Clinic Cancer Care at Regional Cancer Center
state: Wisconsin
city: Green Bay
country: United States
facility: St. Vincent Hospital Regional Cancer Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Center for Cancer and Blood
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
state: Wisconsin
city: Marshfield
country: United States
facility: Marshfield Clinic - Marshfield Center
state: Wisconsin
city: Marshfield
country: United States
facility: Saint Joseph's Hospital
state: Wisconsin
city: Mequon
country: United States
facility: Columbia Saint Mary's Hospital - Ozaukee
state: Wisconsin
city: Milwaukee
country: United States
facility: Columbia-Saint Mary's Cancer Care Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Minocqua
country: United States
facility: Marshfield Clinic - Lakeland Center
state: Wisconsin
city: Rhinelander
country: United States
facility: Ministry Medical Group at Saint Mary's Hospital
state: Wisconsin
city: Rice Lake
country: United States
facility: Marshfield Clinic - Indianhead Center
state: Wisconsin
city: Stevens Point
country: United States
facility: Marshfield Clinic at Saint Michael's Hospital
state: Wisconsin
city: Waukesha
country: United States
facility: Waukesha Memorial Hospital Regional Cancer Center
state: Wisconsin
city: Weston
country: United States
facility: Diagnostic and Treatment Center
state: Wisconsin
city: Weston
country: United States
facility: Marshfield Clinic - Weston Center
state: Wisconsin
Study officials:
affiliation: University of Virginia
name: David Schiff, MD
role: STUDY_CHAIR
References: