Radiation Therapy With or Without Temozolomide in Treating Older Patients With Newly Diagnosed Glioblastoma Multiforme

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
European Organisation for Research and Treatment of Cancer - EORTC
Trans-Tasman Radiation Oncology Group (TROG)
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00482677
First received: June 4, 2007
Last updated: February 19, 2014
Last verified: February 2014
  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. Giving radiation therapy together with temozolomide may kill more tumor cells. It is not yet known whether radiation therapy and temozolomide are more effective than radiation therapy alone in treating glioblastoma multiforme.

PURPOSE: This randomized phase III trial is studying radiation therapy and temozolomide to see how well they work compared with radiation therapy alone in treating patients with newly diagnosed glioblastoma multiforme.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: temozolomide
Genetic: DNA methylation analysis
Procedure: quality-of-life assessment
Radiation: Radiation
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase III Study of Temozolomide and Short-Course Radiation Versus Short-Course Radiation Alone In The Treatment of Newly Diagnosed Glioblastoma Multiforme in Elderly Patients

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 7 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 7 years ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 7 years ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: 7 years ] [ Designated as safety issue: No ]
  • Methylation status of the O6-methylguanine-DNA methyltransferase promoter [ Time Frame: 7 years ] [ Designated as safety issue: No ]

Enrollment: 562
Study Start Date: May 2007
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Temozolomide
Temozolomide and short course radiation
Drug: temozolomide
Temozolomide (concurrent with radiation) 75 mg/m2 PO 3 weeks once a day, daily, from the first day to the last day of radiotherapy, but for no longer than 28 days
Genetic: DNA methylation analysis
A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms
Procedure: quality-of-life assessment
prior to randomization until end of study
Active Comparator: Radiation
Short course radiation alone
Genetic: DNA methylation analysis
A stratified log-rank test, adjusting for the stratification factors (except centre) plus MGMT promoter methylation status, will be used as the primary method to compare the overall survival between the two arms
Procedure: quality-of-life assessment
prior to randomization until end of study
Radiation: Radiation
Short course radiotherapy

Detailed Description:

OBJECTIVES:

Primary

  • Compare overall survival rates in older patients with newly diagnosed glioblastoma multiforme treated with short-course radiotherapy with or without temozolomide.

Secondary

  • Compare progression-free survival of patients treated with these regimens.
  • Compare the nature, severity, and frequency of adverse events in patients treated with these regimens.
  • Compare the quality of life of patient treated with these regimens.
  • Determine the methylation status of the O6-methylguanine-DNA methyltransferase promoter.

OUTLINE: This is a multicenter, randomized study. Patients are stratified according to center, age (65-70 years vs 71-75 years vs ≥ 76 years), ECOG performance status (0-1 vs 2), and extent of resection at surgery (biopsy only vs complete or incomplete resection). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients undergo radiotherapy once daily on days 1-5, 8-12, and 15-19 in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients undergo radiotherapy as in arm I and receive oral temozolomide once daily on days 1-21.

Beginning 4 weeks after completion of radiotherapy and temozolomide, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with temozolomide alone repeats every 28 days for up to 12 months in the absence of disease progression or unacceptable toxicity.

Patients complete quality of life questionnaires at baseline and periodically during study treatment.

Tissue samples are collected at baseline and analyzed for methylation status of the O6-methylguanine-DNA methyltransferase promoter.

After completion of study treatment, patients are followed every 3 months.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histopathologically confirmed glioblastoma multiforme

    • Grade IV disease by WHO classification
    • Newly diagnosed disease
  • Initial diagnostic surgery or biopsy performed within the past 4 weeks
  • Not a candidate for standard radiotherapy (60Gy/30 fractions over 6 weeks) in combination with temozolomide

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Absolute granulocyte count ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • Bilirubin ≤ 1.5 times ULN
  • ALT and AST < 2.5 times ULN
  • No known hypersensitivity to temozolomide or compounds with similar chemical composition to temozolomide
  • No history of other malignancies except adequately treated nonmelanoma skin cancer, curatively treated in situ cancer of the cervix, or other curatively treated solid tumors with no evidence of disease for at least 5 years
  • No serious active infection (e.g., wound infection requiring parenteral antibiotics) or other serious underlying medical conditions that would preclude study treatment
  • No other condition (e.g., psychological or geographical) that would preclude study compliance

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy
  • No prior radiotherapy
  • No prior or concurrent investigational therapy
  • No concurrent surgical procedures for tumor debulking
  • No concurrent stereotactic boost radiotherapy
  • No other concurrent chemotherapy, immunotherapy, or biological therapy
  • No concurrent epoetin alfa
  • Concurrent corticosteroids allowed provided the patient has been on a stable or decreasing dose for at least 14 days
  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: NCT00482677

Locations
Canada, Alberta
Tom Baker Cancer Centre
Calgary, Alberta, Canada, T2N 4N2
Canada, British Columbia
BCCA - Fraser Valley Cancer Centre
Surrey, British Columbia, Canada, V3V 1Z2
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
BCCA - Vancouver Island Cancer Centre
Victoria, British Columbia, Canada, V8R 6V5
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
Atlantic Health Sciences Corporation
Saint John, New Brunswick, Canada, E2L 4L2
Canada, Nova Scotia
QEII Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Juravinski Cancer Centre at Hamilton Health Sciences
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Odette Cancer Centre
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
CHUM - Hopital Notre-Dame
Montreal, Quebec, Canada, H2L 4M1
McGill University - Dept. Oncology
Montreal, Quebec, Canada, H2W 1S6
Centre hospitalier universitaire de Sherbrooke
Sherbrooke, Quebec, Canada, J1H 5N4
Centre hospitalier regional de Trois-Rivieres
Trois-Rivieres, Quebec, Canada, G8Z 3R9
Germany
Klinikum Der J.W. Goethe Universitaet
Frankfurt, Germany, 60590
Universitaetsklinikum Freiburg
Freiburg, Germany, 79106
Universitaetsklinikum Leipzig
Leipzig, Germany, 04103
Universitaetsklinikum Tuebingen
Tuebingen, Germany, 72076
Japan
Hiroshima University Hospital
Hiroshima, Japan, 734-8551
Netherlands
Maastro - Maastricht Radiation Oncology
Maastricht, Netherlands, 6201
Sponsors and Collaborators
NCIC Clinical Trials Group
European Organisation for Research and Treatment of Cancer - EORTC
Trans-Tasman Radiation Oncology Group (TROG)
Investigators
Study Chair: Normand Laperriere, MD, FRCPC Princess Margaret Hospital, Canada
Study Chair: James R. Perry, MD, FRCPC Edmond Odette Cancer Centre at Sunnybrook
Study Chair: Alba A. Brandes, MD Ospedale Bellaria
Study Chair: Johan Menten, MD, PhD U.Z. Gasthuisberg
  More Information

Additional Information:
No publications provided by NCIC Clinical Trials Group

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00482677     History of Changes
Obsolete Identifiers: NCT00493207
Other Study ID Numbers: CE6, CAN-NCIC-CE6, EORTC-26062-22061, TROG 08.02, SPRI-CAN-NCIC-CE.6, CDR0000547163
Study First Received: June 4, 2007
Last Updated: February 19, 2014
Health Authority: Canada: NCIC Clinical Trials Group

Keywords provided by NCIC Clinical Trials Group:
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Glioblastoma
Nervous System Neoplasms
Central Nervous System Neoplasms
Astrocytoma
Glioma
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 August 27, 2014