Radiation Therapy or Temozolomide in Treating Patients With Gliomas

October 11, 2016 updated by: European Organisation for Research and Treatment of Cancer - EORTC

Primary Chemotherapy With Temozolomide Versus Radiotherapy in Patients With Low Grade Gliomas After Stratification for Genetic 1p Loss: A Phase III Study

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

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

Secondary

  • 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

Enrollment (Actual)

709

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: radiotherapy
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival
Time Frame: 5 years
5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival
Time Frame: 5 years
5 years
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
every 3 months until progression, and then every 6 months until death
Mini-Mental State Examination
Time Frame: every 3 months until progression, and then every 6 months until death
every 3 months until progression, and then every 6 months until death
Adverse events as measured by CTCAE v3.0
Time Frame: As indicated in the protocol
As indicated in the protocol

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC

Collaborators

NCIC Clinical Trials Group
Trans Tasman Radiation Oncology Group
British Medical Research Council

Investigators

  • Study Chair: Brigitta Baumert, MD, PhD, Maastricht University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2005

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

May 1, 2014

Study Registration Dates

First Submitted

September 15, 2005

First Submitted That Met QC Criteria

September 15, 2005

First Posted (Estimate)

September 16, 2005

Study Record Updates

Last Update Posted (Estimate)

October 12, 2016

Last Update Submitted That Met QC Criteria

October 11, 2016

Last Verified

October 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EORTC-22033-26033
  • 2004-002714-11 (EudraCT Number)
  • CAN-NCIC-CE5
  • TROG 06.01
  • MRC-BR13

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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