Radiation Therapy or Temozolomide in Treating Patients With Gliomas

NCT00182819 | Completed Phase 3

• 5 other identifiers: EORTC-22033-260332004-002714-11CAN-NCIC-CE5TROG 06.01MRC-BR13
• Study Type: interventional
• Target: 709
• Locations: 18 countries
• Sites: 88

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult oligodendroglioma; adult diffuse astrocytoma; adult mixed glioma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  5 years

Secondary Outcomes (4)

• Overall survival

  5 years

• Quality of life as measured by QLQ-C30 v3.0 and EORTC BN-20

  every 3 months until progression, and then every 6 months until death

• Mini-Mental State Examination

  every 3 months until progression, and then every 6 months until death

• Adverse events as measured by CTCAE v3.0

  As indicated in the protocol

Study Arms (2)

radiotherapy

OTHER

Radiotherapy (control arm), 50.4 Gy, standard fractionation (28 x 1.8 Gy), conformal techniques

Radiation: radiation therapy

Temozolomide

EXPERIMENTAL

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

Drug: temozolomide

Interventions

temozolomide DRUG

Temozolomide 75 mg/m2 daily x 21 days, q 28 days until progression or for max. 12 cycles

Temozolomide

radiation therapy RADIATION

50.4 Gy, standard fractionation (28 x 1.8 Gy), conformal techniques

radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * 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 PATIENT CHARACTERISTICS: Age * 18 and over Performance status * WHO 0-2 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 Hepatic * 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 Renal * Creatinine ≤ 1.5 times ULN Other * 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) PRIOR CONCURRENT THERAPY: 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 Chemotherapy * No prior chemotherapy * No other concurrent chemotherapy, including adjuvant chemotherapy for patients randomized to undergo radiotherapy Endocrine therapy * Not specified Radiotherapy * No prior radiotherapy to the brain * No concurrent integrated boost with intensity-modulated radiotherapy Surgery * Recovered from prior surgery * No concurrent surgical tumor debulking Other * 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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead
• NCIC Clinical Trials Group: collaborator
• British Medical Research Council: collaborator
• Trans Tasman Radiation Oncology Group: collaborator

Study Sites (89)

Prince of Wales Private Hospital

Randwick, New South Wales, 2031, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Sydney Cancer Centre at Royal Prince Alfred Hospital

Sydney, New South Wales, 2050, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Mater Adult Hospital

South Brisbane, Queensland, 4101, Australia

Location

Peter MacCallum Cancer Centre

East Melbourne, Victoria, 3002, Australia

Location

Austin and Repatriation Medical Centre

Heidelberg West, Victoria, 3084, Australia

Location

Alfred Hospital

Prahran, Victoria, 3181, Australia

Location

Sir Charles Gairdner Hospital - Nedlands

Nedlands, Western Australia, 6009, Australia

Location

Liverpool Hospital

Liverpool, BC NSW 1871, Australia

Location

Medical University Vienna - General Hospital AKH

Vienna, 1090, Austria

Location

Hopital Universitaire Erasme

Brussels, 1070, Belgium

Location

Universitair Ziekenhuis Brussel

Brussels, 1090, Belgium

Location

U.Z. Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Saint John Regional Hospital

Saint John, New Brunswick, E2L 4L2, Canada

Location

Nova Scotia Cancer Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Margaret and Charles Juravinski Cancer Centre

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program at London Health Sciences Centre

London, Ontario, N6A 4L6, Canada

Location

Edmond Odette Cancer Centre at Sunnybrook

Toronto, Ontario, M4N 3M5, Canada

Location

Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

Hopital Notre-Dame du CHUM

Montreal, Quebec, H2L 4M1, Canada

Location

Mcgill University Health Centre - Gerald Bronfman Centre - Dept Of Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Allan Blair Cancer Centre at Pasqua Hospital

Regina, Saskatchewan, S4T 7T1, Canada

Location

BC Cancer Agency

Vancouver, V5Z4E9, Canada

Location

National Cancer Institute of Egypt

Cairo, Egypt

Location

CHU de Bordeaux - Groupe Hospitalier Saint-André - Hopital Saint-Andre

Bordeaux, 33075, France

Location

Institut Bergonie

Bordeaux, 33076, France

Location

CHU de Grenoble - Hopital de la Tronche

Grenoble, 38043, France

Location

CHU de la Timone

Marseille, 13385, France

Location

Centre Regional Rene Gauducheau

Nantes-Saint Herblain, 44805, France

Location

Assistance Publique - Hopitaux de Paris - La Pitie Salpetriere

Paris, 75651, France

Location

Centre Eugene Marquis

Rennes, 35042, France

Location

Centre Paul Strauss

Strasbourg, 67085, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitatsklinikum Heidelberg

Heidelberg, D-69120, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitaetskliniken Regensburg

Regensburg, 93053, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

National Institute Of Neurosurgery

Budapest, 1145, Hungary

Location

Rambam Health Care Campus, Oncology Institute

Haifa, 31096, Israel

Location

Ospedale Bellaria

Bologna, I-40139, Italy

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Istituto Regina Elena / Istituti Fisioterapici Ospitalieri

Roma, 00144, Italy

Location

Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino

Turin, 10126, Italy

Location

Centre Francois Baclesse

Esch / Alzette, 4240, Luxembourg

Location

Vrije Universiteit Medisch Centrum

Amsterdam, 1007MB, Netherlands

Location

Academisch Medisch Centrum - Universiteit van Amsterdam

Amsterdam, 1105 AZ, Netherlands

Location

University Medical Center Groningen

Groningen, 9713 GZ, Netherlands

Location

Maastro Clinic - Maastricht Radiation Oncology

Maastricht, 6201 BN, Netherlands

Location

Radboud University Medical Center Nijmegen

Nijmegen, 6500 HB, Netherlands

Location

Erasmus MC Cancer Institute - location Daniel den Hoed

Rotterdam, 3008 AE, Netherlands

Location

Medisch Centrum Haaglanden - Westeinde

The Hague, 2501 CK, Netherlands

Location

Dr. Bernard Verbeeten Instituut

Tilburg, 5042 SB, Netherlands

Location

Canterbury Health Laboratories

Christchurch, New Zealand

Location

Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, SA

Lisbon, 1099-023 Codex, Portugal

Location

National University of Singapore

Singapore, 119228, Singapore

Location

ICO Badalona - Hospital Germans Trias i Pujol (Institut Catala D'Oncologia)

Badalona - (Barcelona), 08916, Spain

Location

Hospital General Vall D'Hebron

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital Clinico Universitario de Barcelona

Barcelona, 08036, Spain

Location

ICO Girona - Hospital Doctor Josep Trueta (Institut Catala D'Oncologia)

Girona, 17007, Spain

Location

ICO L'Hospitalet - Hospital Duran i Reynals (Institut Catala D'Oncologia)

L'Hospitalet de Llobregat, 08907, Spain

Location

University Hospital of Linkoping

Linköping, S-581 85, Sweden

Location

Skane University Hospital

Lund, SE-22185, Sweden

Location

Umea Universitet

Umeå, SE-901 87, Sweden

Location

Uppsala University Hospital

Uppsala, SE-75185, Sweden

Location

Oncology Institute of Southern Switzerland - Ospedale Regionale Bellinzona e Valli

Bellinzona, 6500, Switzerland

Location

Centre Hospitalier Universitaire Vaudois - Lausanne

Lausanne, 1011, Switzerland

Location

UniversitaetsSpital Zurich

Zurich, 8091, Switzerland

Location

University Hospitals Bristol NHS Foundation Trust - Bristol Haematology And Oncology Centre

Bristol, Avon, BS2 8ED, United Kingdom

Location

Clatterbridge Centre for Oncology

Bebington, Wirral, England, CH63 4JY, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, England, CB2 0QQ, United Kingdom

Location

Leeds Cancer Centre at St. James's University Hospital

Leeds, England, LS9 7TF, United Kingdom

Location

University College Hospital

London, England, NW1 2PG, United Kingdom

Location

Royal Marsden - London

London, England, SW3 6JJ, United Kingdom

Location

Christie Hospital

Manchester, England, M20 4BX, United Kingdom

Location

James Cook University Hospital

Middlesbrough, England, TS4 3BW, United Kingdom

Location

Cancer Research Centre at Weston Park Hospital

Sheffield, England, S10 2SJ, United Kingdom

Location

Royal Marsden - Surrey

Sutton, England, SM2 5PT, United Kingdom

Location

Gloucestershire Hospital NHS Foundation Trust - Cheltenham General Hospital

Cheltenham, GL53 7AN, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Oxford University Hospitals NHS Trust - Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Lancashire Teaching Hospitals NHS Foundation Trust - Royal Preston Hospital

Preston, PR2 9HT, United Kingdom

Location

Related Publications (5)

• Musat E, Roelofs E, Bar-Deroma R, Fenton P, Gulyban A, Collette L, Stupp R, Weber DC, Bernard Davis J, Aird E, Baumert BG. Dummy run and conformity indices in the ongoing EORTC low-grade glioma trial 22033-26033: First evaluation of quality of radiotherapy planning. Radiother Oncol. 2010 May;95(2):218-24. doi: 10.1016/j.radonc.2010.03.005. Epub 2010 Apr 6.

  PMID: 20378192 BACKGROUND

• Fairchild A, Weber DC, Bar-Deroma R, Gulyban A, Fenton PA, Stupp R, Baumert BG. Quality assurance in the EORTC 22033-26033/CE5 phase III randomized trial for low grade glioma: the digital individual case review. Radiother Oncol. 2012 Jun;103(3):287-92. doi: 10.1016/j.radonc.2012.04.002. Epub 2012 May 3.

  PMID: 22560713 BACKGROUND

• Gao Y, Weenink B, van den Bent MJ, Erdem-Eraslan L, Kros JM, Sillevis Smitt P, Hoang-Xuan K, Brandes AA, Vos M, Dhermain F, Enting R, Ryan GF, Chinot O, Ben Hassel M, van Linde ME, Mason WP, Gijtenbeek JMM, Balana C, von Deimling A, Gorlia T, Stupp R, Hegi ME, Baumert BG, French PJ. Expression-based intrinsic glioma subtypes are prognostic in low-grade gliomas of the EORTC22033-26033 clinical trial. Eur J Cancer. 2018 May;94:168-178. doi: 10.1016/j.ejca.2018.02.023. Epub 2018 Mar 20.

  PMID: 29571083 DERIVED

• Baumert BG, Hegi ME, van den Bent MJ, von Deimling A, Gorlia T, Hoang-Xuan K, Brandes AA, Kantor G, Taphoorn MJB, Hassel MB, Hartmann C, Ryan G, Capper D, Kros JM, Kurscheid S, Wick W, Enting R, Reni M, Thiessen B, Dhermain F, Bromberg JE, Feuvret L, Reijneveld JC, Chinot O, Gijtenbeek JMM, Rossiter JP, Dif N, Balana C, Bravo-Marques J, Clement PM, Marosi C, Tzuk-Shina T, Nordal RA, Rees J, Lacombe D, Mason WP, Stupp R. Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016 Nov;17(11):1521-1532. doi: 10.1016/S1470-2045(16)30313-8. Epub 2016 Sep 27.

  PMID: 27686946 DERIVED

• Reijneveld JC, Taphoorn MJB, Coens C, Bromberg JEC, Mason WP, Hoang-Xuan K, Ryan G, Hassel MB, Enting RH, Brandes AA, Wick A, Chinot O, Reni M, Kantor G, Thiessen B, Klein M, Verger E, Borchers C, Hau P, Back M, Smits A, Golfinopoulos V, Gorlia T, Bottomley A, Stupp R, Baumert BG. Health-related quality of life in patients with high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. Lancet Oncol. 2016 Nov;17(11):1533-1542. doi: 10.1016/S1470-2045(16)30305-9. Epub 2016 Sep 27.

  PMID: 27686943 DERIVED

MeSH Terms

Conditions

Central Nervous System Neoplasms; Oligodendroglioma; Astrocytoma; Glioma

Interventions

Temozolomide; Radiotherapy

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Brigitta Baumert, MD, PhD

  Maastricht University Medical Center

  STUDY CHAIR

• Roger Stupp, MD

  Centre Hospitalier Universitaire Vaudois

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2005
• First Posted: September 16, 2005
• Study Start: July 1, 2005
• Primary Completion: August 1, 2013
• Study Completion: May 1, 2014
• Last Updated: October 12, 2016

Record last verified: 2016-10

Locations

NL (8); SE (4); CA (12); PT (1); HU (1); IT (4); AU (12); SG (1); LU (1); BE (3); CH (3); FR (10); EG (1); IL (1); DE (4); GB (15); ES (6); NZ (1)