Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma

Brain and Central Nervous System Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00978458
• Other study ID #: E3F05
• Secondary ID: ECOG-E3F05
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: November 17, 2009
• Est. completion date: December 31, 2026

Study information

• Verified date: January 2024
• Source: Eastern Cooperative Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 540
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioma
• Nervous System Neoplasms
• Neurotoxicity
• Neurotoxicity Syndromes

Intervention

Drug:
• temozolomide
Given orally

Radiation:
• 3-dimensional conformal radiation therapy
Given once daily 5 days a week for 5½ weeks
• intensity-modulated radiation therapy
Given once daily 5 days a week for 5½ weeks

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Eastern Cooperative Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS)
Primary	Overall survival (OS)
Secondary	Quality of life as assessed by the FACT-BR questionnaire at baseline, annually until disease progression, and at the time of disease progression
Secondary	Neurocognitive functioning as assessed at baseline, annually until disease progression, and at the time of disease progression
Secondary	Correlation of pre-treatment 1p and 19q levels in tumor tissue samples with PFS and OS