Radiation Therapy or Temozolomide in Treating Patients With Gliomas

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00182819
Recruitment Status : Completed
First Posted : September 16, 2005
Last Update Posted : October 12, 2016
NCIC Clinical Trials Group
British Medical Research Council
Trans-Tasman Radiation Oncology Group (TROG)
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

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. It is not yet known whether radiation therapy is more effective than temozolomide in treating gliomas.

PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared to temozolomide in treating patients with gliomas.

Condition or disease Intervention/treatment Phase
Brain and Central Nervous System Tumors Drug: temozolomide Radiation: radiation therapy Phase 3

Detailed Description:



  • Compare the progression-free survival of patients with low-grade gliomas treated with radiotherapy vs temozolomide.


  • Compare the overall survival of patients treated with these regimens.
  • Determine whether the incidence of late toxicity can be decreased in patients who are randomized to receive temozolomide.
  • Compare the toxic effects of these regimens in these patients.
  • Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, chromosome 1p status (deleted vs normal vs undeterminable), contrast enhancement on MRI (yes vs no), age (< 40 years vs ≥ 40 years), and WHO performance status (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo radiotherapy once daily, 5 days a week, for a total of 28 fractions (i.e., 5½ weeks).
  • Arm II: Patients receive oral temozolomide once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline and then every 3 months until disease progression.

After completion of study treatment, patients are followed every 6 months for survival.

Peer Reviewed and Funded or Endorsed by Cancer Research UK

PROJECTED ACCRUAL: A minimum of 699 patients (a total of 466 randomized [233 per treatment arm]) will be accrued for this study within 5 years.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 709 participants
Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Primary Chemotherapy With Temozolomide Versus Radiotherapy in Patients With Low Grade Gliomas After Stratification for Genetic 1p Loss: A Phase III Study
Study Start Date : July 2005
Actual Primary Completion Date : August 2013
Actual Study Completion Date : May 2014

Arm Intervention/treatment
Radiotherapy (control arm), 50.4 Gy, standard fractionation (28 x 1.8 Gy), conformal techniques
Radiation: radiation therapy
50.4 Gy, standard fractionation (28 x 1.8 Gy), conformal techniques

Experimental: Temozolomide
Temozolomide 75 mg/m2 daily x 21 days, q 28 days until progression or for max. 12 cycles (experimental arm)
Drug: temozolomide
Temozolomide 75 mg/m2 daily x 21 days, q 28 days until progression or for max. 12 cycles

Primary Outcome Measures :
  1. Progression-free survival [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 5 years ]
  2. Quality of life as measured by QLQ-C30 v3.0 and EORTC BN-20 [ Time Frame: every 3 months until progression, and then every 6 months until death ]
  3. Mini-Mental State Examination [ Time Frame: every 3 months until progression, and then every 6 months until death ]
  4. Adverse events as measured by CTCAE v3.0 [ Time Frame: As indicated in the protocol ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed low-grade glioma, including any of the following types:

    • Astrocytoma (gemistocytic, fibrillary, or protoplasmatic)
    • Oligoastrocytoma
    • Oligodendroglioma
  • WHO grade II disease
  • Supratentorial tumor location only
  • RTOG neurological function 0-3
  • Not a candidate for surgical treatment alone
  • Requires treatment, as determined by ≥ 1 of the following criteria:

    • Age ≥ 40 years
    • Radiologically-proven progressive lesion
    • New or worsening neurological symptoms other than seizures only (e.g., focal deficits, signs of increased intracranial pressure, or mental deficits)
    • Intractable seizures, defined by both of the following criteria:

      • Experiences persistent seizures that interfere with everyday life activities except driving a car
      • Failed 3 anti-epileptic drug regimens, including ≥ 1 combination regimen
  • Tumor material (paraffin-embedded) or histopathologic slides available



  • 18 and over

Performance status

  • WHO 0-2

Life expectancy

  • Not specified


  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3


  • No chronic hepatitis B or C infection
  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN


  • Creatinine ≤ 1.5 times ULN


  • Not pregnant or nursing
  • Fertile patients must use effective contraception during and for 6 months after completion of study treatment
  • No known HIV positivity
  • No other serious medical condition
  • No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer
  • No psychological, familial, sociological, or geographical condition that would preclude study participation
  • No medical condition that would preclude receiving oral medication (e.g., frequent vomiting or partial bowel obstruction)


Biologic therapy

  • No concurrent growth factors for elevating absolute neutrophil counts for the purpose of temozolomide administration
  • No concurrent epoetin alfa
  • No concurrent immunotherapy or biologic therapy


  • No prior chemotherapy
  • No other concurrent chemotherapy, including adjuvant chemotherapy for patients randomized to undergo radiotherapy

Endocrine therapy

  • Not specified


  • No prior radiotherapy to the brain
  • No concurrent integrated boost with intensity-modulated radiotherapy


  • Recovered from prior surgery
  • No concurrent surgical tumor debulking


  • No prior randomization to this study
  • No other concurrent investigational drugs
  • No concurrent regular use of agents known to be radiosensitizers or radioprotectors (e.g., cyclooxygenase-2 inhibitors, thalidomide, or amifostine) during study radiotherapy

    • Occasional use of nonsteroidal anti-inflammatory drugs for pain allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00182819

  Hide Study Locations
Australia, New South Wales
Prince of Wales Private Hospital
Randwick, New South Wales, Australia, 2031
Royal North Shore Hospital
St. Leonards, New South Wales, Australia, 2065
Sydney Cancer Centre at Royal Prince Alfred Hospital
Sydney, New South Wales, Australia, 2050
Calvary Mater Newcastle
Waratah, New South Wales, Australia, 2298
Australia, Queensland
Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia, 4029
Princess Alexandra Hospital
Brisbane, Queensland, Australia, 4102
Mater Adult Hospital
South Brisbane, Queensland, Australia, 4101
Australia, Victoria
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia, 3002
Austin and Repatriation Medical Centre
Heidelberg West, Victoria, Australia, 3084
Alfred Hospital
Prahran, Victoria, Australia, 3181
Australia, Western Australia
Sir Charles Gairdner Hospital - Nedlands
Nedlands, Western Australia, Australia, 6009
Liverpool Hospital
Liverpool, Australia, BC NSW 1871
Medical University Vienna - General Hospital AKH
Vienna, Austria, 1090
Hopital Universitaire Erasme
Brussels, Belgium, 1070
Universitair Ziekenhuis Brussel
Brussels, Belgium, 1090
U.Z. Leuven - Campus Gasthuisberg
Leuven, Belgium, 3000
Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
Saint John Regional Hospital
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Nova Scotia
Nova Scotia Cancer Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Edmond Odette Cancer Centre at Sunnybrook
Toronto, Ontario, Canada, M4N 3M5
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Hopital Notre-Dame du CHUM
Montreal, Quebec, Canada, H2L 4M1
Mcgill University Health Centre - Gerald Bronfman Centre - Dept Of Oncology
Montreal, Quebec, Canada, H2W 1S6
Canada, Saskatchewan
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada, S4T 7T1
BC Cancer Agency
Vancouver, Canada, V5Z4E9
National Cancer Institute of Egypt
Cairo, Egypt
CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre
Bordeaux, France, 33075
Institut Bergonie
Bordeaux, France, 33076
CHU de Grenoble - Hopital de la Tronche
Grenoble, France, 38043
CHU de la Timone
Marseille, France, 13385
Centre Regional Rene Gauducheau
Nantes-Saint Herblain, France, 44805
Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere
Paris, France, 75651
Centre Eugene Marquis
Rennes, France, 35042
Centre Paul Strauss
Strasbourg, France, 67085
Institut Claudius Regaud
Toulouse, France, 31059
Gustave Roussy
Villejuif, France, 94805
Universitatsklinikum Heidelberg
Heidelberg, Germany, D-69120
Universitaetsklinikum Leipzig
Leipzig, Germany, 04103
Universitaetskliniken Regensburg
Regensburg, Germany, 93053
Universitaetsklinikum Tuebingen
Tuebingen, Germany, 72076
National Institute Of Neurosurgery
Budapest, Hungary, 1145
Rambam Health Care Campus, Oncology Institute
Haifa, Israel, 31096
Ospedale Bellaria
Bologna, Italy, I-40139
Ospedale San Raffaele
Milano, Italy, 20132
Istituto Regina Elena / Istituti Fisioterapici Ospitalieri
Roma, Italy, 00144
Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
Turin, Italy, 10126
Centre Francois Baclesse
Esch / Alzette, Luxembourg, 4240
Vrije Universiteit Medisch Centrum
Amsterdam, Netherlands, 1007MB
Academisch Medisch Centrum - Universiteit van Amsterdam
Amsterdam, Netherlands, 1105 AZ
Medisch Centrum Haaglanden - Westeinde
Den Haag, Netherlands, 2501 CK
University Medical Center Groningen
Groningen, Netherlands, 9713 GZ
Maastro Clinic - Maastricht Radiation Oncology
Maastricht, Netherlands, 6201 BN
Radboud University Medical Center Nijmegen
Nijmegen, Netherlands, 6500 HB
Erasmus MC Cancer Institute - location Daniel den Hoed
Rotterdam, Netherlands, 3008 AE
Dr. Bernard Verbeeten Instituut
Tilburg, Netherlands, 5042 SB
New Zealand
Canterbury Health Laboratories
Christchurch, New Zealand
Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, SA
Lisbon, Portugal, 1099-023 Codex
National University of Singapore
Singapore, Singapore, 119228
ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)
Badalona - (Barcelona), Spain, 08916
Hospital General Vall D'Hebron
Barcelona, Spain, 08035
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital Clinico Universitario de Barcelona
Barcelona, Spain, 08036
ICO Girona - Hospital Doctor Josep Trueta (Institut Catala D'Oncologia)
Girona, Spain, 17007
ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)
L'Hospitalet de Llobregat, Spain, 08907
University Hospital of Linkoping
Linkoping, Sweden, S-581 85
Skane University Hospital
Lund, Sweden, SE-22185
Umea Universitet
Umea, Sweden, SE-901 87
Uppsala University Hospital
Uppsala, Sweden, SE-75185
Oncology Institute of Southern Switzerland - Ospedale Regionale Bellinzona e Valli
Bellinzona, Switzerland, 6500
Centre Hospitalier Universitaire Vaudois - Lausanne
Lausanne, Switzerland, 1011
UniversitaetsSpital Zurich
Zurich, Switzerland, 8091
United Kingdom
University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre
Bristol, Avon, United Kingdom, BS2 8ED
Clatterbridge Centre for Oncology
Bebington, Wirral, England, United Kingdom, CH63 4JY
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 0QQ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
University College Hospital
London, England, United Kingdom, NW1 2PG
Royal Marsden - London
London, England, United Kingdom, SW3 6JJ
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
James Cook University Hospital
Middlesbrough, England, United Kingdom, TS4 3BW
Cancer Research Centre at Weston Park Hospital
Sheffield, England, United Kingdom, S10 2SJ
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Gloucestershire Hospital NHS Foundation Trust - Cheltenham General Hospital
Cheltenham, United Kingdom, GL53 7AN
Western General Hospital
Edinburgh, United Kingdom, EH4 2XU
Royal Free Hospital
London, United Kingdom, NW3 2QG
Oxford University Hospitals NHS Trust - Churchill Hospital
Oxford, United Kingdom, OX3 7LE
Lancashire Teaching Hospitals NHS Foundation Trust - Royal Preston Hospital
Preston, United Kingdom, PR2 9HT
Sponsors and Collaborators
European Organisation for Research and Treatment of Cancer - EORTC
NCIC Clinical Trials Group
British Medical Research Council
Trans-Tasman Radiation Oncology Group (TROG)
Study Chair: Brigitta Baumert, MD, PhD Maastricht University Medical Center
Study Chair: Roger Stupp, MD Centre Hospitalier Universitaire Vaudois

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC Identifier: NCT00182819     History of Changes
Other Study ID Numbers: EORTC-22033-26033
2004-002714-11 ( EudraCT Number )
TROG 06.01
First Posted: September 16, 2005    Key Record Dates
Last Update Posted: October 12, 2016
Last Verified: October 2016

Keywords provided by European Organisation for Research and Treatment of Cancer - EORTC:
adult oligodendroglioma
adult diffuse astrocytoma
adult mixed glioma

Additional relevant MeSH terms:
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms by Site
Nervous System Diseases
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents