Phase III Trial of Anaplastic Glioma Without 1p/19q Loss of Heterozygosity (LOH)
- Conditions
- Brain and Central Nervous System Tumors
- Interventions
- Genetic: DNA methylation analysisOther: laboratory biomarker analysisRadiation: radiation therapyProcedure: quality-of-life assessmentProcedure: adjuvant therapy
- Registration Number
- NCT00626990
- Brief Summary
RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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. Giving radiation therapy together with temozolomide may kill more tumor cells. It is not yet known whether giving temozolomide during and/or after radiation therapy is more effective than radiation therapy alone in treating anaplastic glioma.
PURPOSE: This randomized phase III trial is studying giving temozolomide during and/or after radiation therapy to see how well it works compared to radiation therapy alone in treating patients with anaplastic glioma.
- Detailed Description
OBJECTIVES:
Primary
* To assess whether concurrent radiotherapy with daily temozolomide improves overall survival as compared to no daily temozolomide in patients with non-1p/19q deleted anaplastic glioma.
* To assess whether adjuvant temozolomide improves survival as compared to no adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma.
Secondary
* To assess whether concurrent and adjuvant temozolomide prolongs progression-free survival and neurological deterioration-free survival in patients with non-1p/19q deleted anaplastic glioma.
* To assess the safety of concurrent and adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma, including late effects on cognition.
* To assess the impact of concurrent and adjuvant temozolomide on the quality of life of patients with non-1p/19q deleted anaplastic glioma.
OUTLINE: This is a multicenter study. Patients are stratified according to institution, World Health Organization (WHO) performance status (0 vs \> 0), age (≤ 50 vs \> 50), presence of 1p LOH only (yes vs no), presence of oligodendroglial elements (yes vs no), and O6-methylguanine-DNA methyltransferase promoter methylation status (methylated vs unmethylated vs indeterminate). Patients are randomized to 1 of 4 treatment arms.
* Arm I: Patients undergo radiotherapy\* once daily, 5 days a week, for 6.5 weeks (total of 33 fractions).
* Arm II: Patients undergo radiotherapy\* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy).
* Arm III: Patients undergo radiotherapy\* once daily, 5 days a week for 6.5 weeks (total of 33 fractions). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.
* Arm IV: Patients undergo radiotherapy\* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.
* Patients must begin radiotherapy within 8 days after randomization and within 7 weeks after surgery.
In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.
Patients complete quality-of-life questionnaires, including EORTC core quality of life questionnaire (QLQ-C30) version 3, EORTC brain cancer module (BCM20), and the Mini Mental Status Exam at baseline, 4 weeks after the completion of radiotherapy, and then every 3 months for 5 years.
Tissue samples are collected at baseline for histology review, 1p/19q analysis, methylation status of the O6-methylguanine-DNA methyltransferase promoter, and isocitrate dehydrogenase mutation analysis.
After completion of study treatment, patients are followed every 3 months.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 751
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Radiotherapy (RT) alone radiation therapy radiation therapy alone RT & Concurrent CT DNA methylation analysis Radiotherapy and concurrent temozolomide chemotherapy Radiotherapy (RT) alone DNA methylation analysis radiation therapy alone RT + Adjuvant CT radiation therapy Radiotherapy plus adjuvant temozolomide chemotherapy RT & Concurrent CT laboratory biomarker analysis Radiotherapy and concurrent temozolomide chemotherapy RT & Concurrent CT radiation therapy Radiotherapy and concurrent temozolomide chemotherapy RT & Concurrent CT quality-of-life assessment Radiotherapy and concurrent temozolomide chemotherapy Radiotherapy (RT) alone laboratory biomarker analysis radiation therapy alone Radiotherapy (RT) alone quality-of-life assessment radiation therapy alone RT & Concurrent CT + adjuvant CT DNA methylation analysis Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy RT + Adjuvant CT DNA methylation analysis Radiotherapy plus adjuvant temozolomide chemotherapy RT + Adjuvant CT laboratory biomarker analysis Radiotherapy plus adjuvant temozolomide chemotherapy RT + Adjuvant CT adjuvant therapy Radiotherapy plus adjuvant temozolomide chemotherapy RT + Adjuvant CT quality-of-life assessment Radiotherapy plus adjuvant temozolomide chemotherapy RT & Concurrent CT + adjuvant CT laboratory biomarker analysis Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy RT & Concurrent CT + adjuvant CT adjuvant therapy Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy RT & Concurrent CT + adjuvant CT quality-of-life assessment Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy RT & Concurrent CT + adjuvant CT radiation therapy Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy RT & Concurrent CT temozolomide Radiotherapy and concurrent temozolomide chemotherapy RT + Adjuvant CT temozolomide Radiotherapy plus adjuvant temozolomide chemotherapy RT & Concurrent CT + adjuvant CT temozolomide Radiotherapy and concurrent chemotherapy plus adjuvant temozolomide chemotherapy
- Primary Outcome Measures
Name Time Method Overall Survival as Measured From the Day of Randomization from date from enrollment till the date of death (time till death is up to 10.9 years after patient enrollment in the study) The duration of survival is the time interval between randomization and the date of death due to any cause. Patients not reported dead or lost to follow up will be censored at the date of the last follow up examination.
- Secondary Outcome Measures
Name Time Method Progression-free Survival from randomization till the date of disease progression or death (time till death is up to 10.9 years after patient enrollment in the study) Disease progression is defined as radiological or neurological/clinical progression (whichever occurs first); progression free survival (PFS) is the time interval between the date of randomization and the date of disease progression or death whichever occurs first. If neither event has been observed, the patient is censored at the date of the last follow up examination. Radiological progression was defined as increase of contrast enhancing area on MRI or CT scans of more than 25% as measured by two perpendicular diameters compared to the smallest measurements ever recorded for the same lesion by the same technique. The appearance of new lesions with or without contrast enhancement Neurological/clinical progression was defined as:decrease in WHO performance status,deterioration of neurological functions,appearance of signs/symptoms of increased intracranial pressure,and/or start of corticosteroid or increase of corticosteroid dosage by 50% for control of neurological symptoms.
Neurological Deterioration Free Survival within 2 weeks of randomization; during radiotherapy at week 4 and 6; 4 weeks after the end of radiotherapy; Six monthly after the end of radiotherapy; Prior to each cycle of adjuvant therapy; Every six months after the documentation of first progression. Neurological deterioration is defined as a decrease in WHO performance status as follows:
decrease in WHO performance status
* for patients with baseline WHO performance status 0: deterioration to WHO performance status 2 or worse for which no other explanation is present, and which is maintained for at least three months
* for patients with baseline WHO performance status 1 or 2: deterioration to WHO performance status 3 or worse for which no other explanation is present and which is maintained for at least three months
The date of neurological deterioration will be the first date the persistent decrease in performance status was diagnosed. Neurological deterioration free progression is the time interval between the date of randomization and the date of neurological deterioration or death whichever occurs first. If neither event has been observed, the patient is censored at the date of the last follow up examinationQuality of Life of the Patient from 14 days prior to randomization till five years or death (time till death is up to 10.9 years after patient enrollment in the study) Quality of life was assessed by the EORTC Quality of Life Questionnaire (QLQ-C30) version 3 and the Brain Cancer Module-20
Trial Locations
- Locations (132)
Boston Medical Center
🇺🇸Boston, Massachusetts, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
Massachussets General Hospital Cancer Center
🇺🇸Boston, Massachusetts, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Parkview Hospital
🇺🇸Fort Wayne, Indiana, United States
University of Rochester - James P. Wilmot Cancer Center
🇺🇸Rochester, New York, United States
McFarland Clinic
🇺🇸Ames, Iowa, United States
Northwestern University
🇺🇸Chicago, Illinois, United States
Dixie Medical Center Regional Cancer Center
🇺🇸Saint George, Utah, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
State University of New York Upstate Medical University
🇺🇸New York, New York, United States
Royal Prince Alfred Hospital
🇦🇺Sydney, New South Wales, Australia
St Vincent'S Hospital
🇦🇺Melbourne, Australia
Intermountain Medical Center
🇺🇸Murray, Utah, United States
Cancer Treatment Center
🇺🇸Wooster, Ohio, United States
Highland Hospital
🇺🇸Rochester, New York, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Centre Eugene Marquis
🇫🇷Rennes, France
Addenbrookes Hospital
🇬🇧Cambridge, United Kingdom
Clatterbridge Centre for Oncology NHS Trust
🇬🇧Wirral, United Kingdom
Universitaetsklinikum Bonn
🇩🇪Bonn, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Germany
Austin-Repatriation Medical Centre
🇦🇺Heidelberg, Australia
Princess Alexandra Hospital
🇦🇺Brisbane, Queensland, Australia
Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Nottingham University Hospitals NHS Trust - City Hospital campus
🇬🇧Nottingham, United Kingdom
Derriford Hospital
🇬🇧Plymouth, United Kingdom
Cancercare Manitoba
🇨🇦Winnipeg, Canada
Royal North Shore Hospital
🇦🇺St. Leonards, New South Wales, Australia
Sir Charles Gairdner Hospital
🇦🇺Nedlands, Australia
Alfred Hospital
🇦🇺Prahran, Australia
ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
🇪🇸Barcelona, Spain
Assistance Publique - Hôpitaux de Marseille - C.H.U. De La Timone
🇫🇷Marseille, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom
University Health Network - Oci / Princess Margaret Hospital
🇨🇦Toronto, Canada
Universitaetskliniken Regensburg
🇩🇪Regensburg, Germany
Royal Hobart Hospital
🇦🇺Hobart, Australia
Hospital Clinic Universitari
🇪🇸Barcelona, Spain
Academisch Medisch Centrum - Universiteit van Amsterdam
🇳🇱Amsterdam, Netherlands
C.H.U. de Nancy - Hopital St Julien
🇫🇷Nancy, France
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
🇬🇧Bristol, United Kingdom
St. James'S University Hospital
🇬🇧Leeds, United Kingdom
Tom Baker Cancer Centre
🇨🇦Calgary, Canada
London Regional Cancer Center
🇨🇦London, Canada
Chu Pitie-Salpetriere AP-HP
🇫🇷Paris, France
Universitaetsklinikum Tuebingen
🇩🇪Tuebingen, Germany
Klinikum Bamberg
🇩🇪Bamberg, Germany
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
University of Florida
🇺🇸Gainesville, Florida, United States
LDS Hospital
🇺🇸Salt Lake City, Utah, United States
UCSF University of California San Francisco Medical Center-Mount Zion
🇺🇸San Francisco, California, United States
University Of Utah - Huntsman Cancer Institute
🇺🇸Salt Lake City, Utah, United States
Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
Via Christi Regional Medical Center
🇺🇸Wichita, Kansas, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Memorial Health University Medical Center
🇺🇸Savannah, Georgia, United States
Saint Vincent Oncology Center
🇺🇸Indianapolis, Indiana, United States
Mayo Clinic in Florida
🇺🇸Jacksonville, Florida, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
Oncology Associates PC
🇺🇸Fort Wayne, Indiana, United States
Wesley Medical Center
🇺🇸Wichita, Kansas, United States
St John's Mercy Medical Center
🇺🇸Saint Louis, Missouri, United States
Western Reserve University
🇺🇸Cleveland, Ohio, United States
Cancer Care Center, Incorporated
🇺🇸Salem, Ohio, United States
UHHS-Chagrin Highlands Medical Center
🇺🇸Orange Village, Ohio, United States
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
Cancer Centers of the Carolinas - Eastside
🇺🇸Greenville, South Carolina, United States
Utah Valley Regional Medical Center
🇺🇸Provo, Utah, United States
Gundersen Lutheran
🇺🇸La Crosse, Wisconsin, United States
Flinders Medical Centre
🇦🇺Bedford Park, Australia
Allan Blair Cancer Centre
🇨🇦Saskatoon, Canada
Institut Gustave Roussy
🇫🇷Villejuif, France
UniversitaetsKlinikum Heidelberg
🇩🇪Heidelberg, Germany
Hopital Cantonal Universitaire De Geneve
🇨🇭Geneve, Switzerland
Cheltenham General Hospital
🇬🇧Cheltenham, United Kingdom
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Weston Park Hospital
🇬🇧Sheffield, United Kingdom
Royal Devon And Exeter Hospital
🇬🇧Exeter, United Kingdom
Ospedale Bellaria
🇮🇹Bologna, Italy
Istituto Scientifico H.S. Raffaele
🇮🇹Milano, Italy
Azienda Ospedaliera San Giovanni Battista Di Torino-Universita Di Torino
🇮🇹Torino, Italy
Arizona Oncology Services Foundation
🇺🇸Phoenix, Arizona, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
June E. Nylen Cancer Center
🇺🇸Sioux City, Iowa, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Summa Barberton Hospital
🇺🇸Barberton, Ohio, United States
Akron City Hospital - Summa Health System
🇺🇸Akron, Ohio, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Southwest General Health Center Ireland Cancer Center
🇺🇸Middleburg Heights, Ohio, United States
UHHS - Westlake Medical Center
🇺🇸Westlake, Ohio, United States
Penn State M.S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Reading Hospital and Medical Center
🇺🇸West Reading, Pennsylvania, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Methodist Hospital
🇺🇸Houston, Texas, United States
Virginia Mason CCOP
🇺🇸Seattle, Washington, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Saint Joseph Mercy Hospital
🇺🇸Ann Arbor, Michigan, United States
Methodist Estabrook Cancer Center
🇺🇸Omaha, Nebraska, United States
Froedtert and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Florida Hospital
🇺🇸Orlando, Florida, United States
Maine Medical Center
🇺🇸Scarborough, Maine, United States
ZNA Middelheim
🇧🇪Antwerpen, Belgium
Cliniques Universitaires St. Luc
🇧🇪Brussels, Belgium
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Medisch Centrum Haaglanden - Westeinde
🇳🇱Den Haag, Netherlands
Radboud University Nijmegen Medical Centre
🇳🇱Nijmegen, Netherlands
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Saint Vincent Hospital
🇺🇸Green Bay, Wisconsin, United States
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Cancer Centers of the Carolinas - Seneca
🇺🇸Seneca, South Carolina, United States
Maastro Clinic - Maastricht Radiation Oncology
🇳🇱Maastricht, Netherlands
Erasmus MC - Daniel den Hoed Cancer Center
🇳🇱Rotterdam, Netherlands
Dartmouth Hitchcock Medical Center
🇺🇸Lebanon, New Hampshire, United States
University Of Wisconsin Comprehensive Cancer Center
🇺🇸Madison, Wisconsin, United States
Cancer Centers of the Carolinas - Greer Radiation Oncology
🇺🇸Greer, South Carolina, United States
Vrije Universiteit Medisch Centrum
🇳🇱Amsterdam, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Saint Mary's Hospital
🇺🇸Green Bay, Wisconsin, United States
West Michigan Cancer Center
🇺🇸Kalamazoo, Michigan, United States
Universitair Ziekenhuis Brussel
🇧🇪Brussels, Belgium
Clinique Notre-Dame
🇧🇪Charleroi, Belgium
Algemeen Ziekenhuis Sint Lucas
🇧🇪Gent, Belgium
U.Z. Gasthuisberg
🇧🇪Leuven, Belgium
Universitaetsspital
🇨🇭Zurich, Switzerland
Spartanburg Regional Medical Center
🇺🇸Spartanburg, South Carolina, United States
Waukesha Memorial Hospital
🇺🇸Waukesha, Wisconsin, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
Cancer Centers of the Carolinas - Faris Road
🇺🇸Greenville, South Carolina, United States
UPMC - Heritage Valley Health System - The Medical Center
🇺🇸Beaver, Pennsylvania, United States