Radiation Therapy or Temozolomide in Treating Patients With Gliomas

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by European Organisation for Research and Treatment of Cancer - EORTC.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
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
ClinicalTrials.gov Identifier:
NCT00182819
First received: September 15, 2005
Last updated: February 6, 2012
Last verified: February 2012
  Purpose

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 Intervention Phase
Brain and Central Nervous System Tumors
Drug: temozolomide
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: 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

Resource links provided by NLM:


Further study details as provided by European Organisation for Research and Treatment of Cancer - EORTC:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Mini-Mental State Examination [ Time Frame: every 3 months until progression, and then every 6 months until death ] [ Designated as safety issue: No ]
  • Adverse events as measured by CTCAE v3.0 [ Time Frame: As indicated in the protocol ] [ Designated as safety issue: Yes ]

Enrollment: 709
Study Start Date: July 2005
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00182819

  Hide Study Locations
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, 2310
Australia, Queensland
Princess Alexandra Hospital
Brisbane, Queensland, Australia, 4102
Royal Brisbane and Women's Hospital
Brisbane, Queensland, Australia, 4029
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, 3081
Alfred Hospital
Melbourne, Victoria, Australia, 3004
Australia, Western Australia
Sir Charles Gairdner Hospital - Nedlands
Nedlands, Western Australia, Australia, 6009
Belgium
Hopital Universitaire Erasme
Brussels, Belgium, 1070
Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Canada, British Columbia
British Columbia Cancer Agency - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
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
Ontario Cancer Institute at Princess Margaret Hospital
Toronto, Ontario, Canada, M4X 1K9
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Hopital Notre-Dame du CHUM
Montreal, Quebec, Canada, H2L 4M1
McGill Cancer Centre at McGill University
Montreal, Quebec, Canada, H2W 1S6
Canada, Saskatchewan
Allan Blair Cancer Centre at Pasqua Hospital
Regina, Saskatchewan, Canada, S4T 7T1
Egypt
National Cancer Institute of Egypt
Cairo, Egypt
France
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
Centre Eugene Marquis
Rennes, France, 35042
Centre Paul Strauss
Strasbourg, France, 67065
Institut Claudius Regaud
Toulouse, France, 31052
Germany
Universitatsklinikum Heidelberg
Heidelberg, Germany, D-69115
Italy
Ospedale Bellaria
Bologna, Italy, I-40139
Istituto Regina Elena
Rome, Italy, 00161
Azienda Sanitaria Ospedale San Giovanni Battista Molinette di Torino
Turin, Italy, 10126
Netherlands
Dr. Bernard Verbeeten Instituut
Tilburg, Netherlands, 5042 SB
New Zealand
Canterbury Health Laboratories
Christchurch, New Zealand
Portugal
Instituto Portugues de Oncologia de Francisco Gentil - Centro Regional de Oncologia de Lisboa, SA
Lisbon, Portugal, 1099-023 Codex
Singapore
National University of Singapore
Singapore, Singapore, 119260
Spain
Hospital Clinic de Barcelona
Barcelona, Spain, 08036
Hospital Clinico Universitario de Barcelona
Barcelona, Spain, 08036
Hospital Universitario La Fe
Valencia, Spain, 46009
Sweden
University Hospital of Linkoping
Linkoping, Sweden, S-581 85
Lund University Hospital
Lund, Sweden, SE-22185
Umea Universitet
Umea, Sweden, SE-901 87
Uppsala University Hospital
Uppsala, Sweden, SE-75185
Switzerland
UniversitaetsSpital Zuerich
Zurich, Switzerland, CH-8091
United Kingdom
Bristol Haematology and Oncology Centre
Bristol, England, United Kingdom, BS2 8ED
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Leeds Cancer Centre at St. James's University Hospital
Leeds, England, United Kingdom, LS9 7TF
University College Hospital
London, England, United Kingdom, NW1 2BU
UCL Cancer Institute
London, England, United Kingdom, WC1E 6DD
Royal Marsden - London
London, England, United Kingdom, SW3 6JJ
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
Clatterbridge Centre for Oncology
Merseyside, England, United Kingdom, CH63 4JY
James Cook University Hospital
Middlesbrough, England, United Kingdom, TS4 3BW
Cancer Research Centre at Weston Park Hospital
Sheffield, England, United Kingdom, S1O 2SJ
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
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)
Investigators
Study Chair: Brigitta Baumert, MD, PhD Maastricht University Medical Center
Study Chair: Roger Stupp, MD Centre Hospitalier Universitaire Vaudois
  More Information

Additional Information:
Publications:
Responsible Party: European Organisation for Research and Treatment of Cancer - EORTC
ClinicalTrials.gov Identifier: NCT00182819     History of Changes
Other Study ID Numbers: EORTC-22033-26033, 2004-002714-11, CAN-NCIC-CE5, TROG 06.01, MRC-BR13
Study First Received: September 15, 2005
Last Updated: February 6, 2012
Health Authority: Canada: Health Canada
European Union: European Medicines Agency

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

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

ClinicalTrials.gov processed this record on July 24, 2014