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Trial record 1 of 1 for:    NCT00482677
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Radiation Therapy With or Without Temozolomide in Treating Older Patients With Newly Diagnosed Glioblastoma Multiforme

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ClinicalTrials.gov Identifier: NCT00482677
Recruitment Status : Completed
First Posted : June 5, 2007
Results First Posted : January 23, 2018
Last Update Posted : July 23, 2019
Sponsor:
Collaborators:
European Organisation for Research and Treatment of Cancer - EORTC
Trans-Tasman Radiation Oncology Group (TROG)
Information provided by (Responsible Party):
Canadian Cancer Trials Group

Tracking Information
First Submitted Date  ICMJE June 4, 2007
First Posted Date  ICMJE June 5, 2007
Results First Submitted Date  ICMJE February 14, 2017
Results First Posted Date  ICMJE January 23, 2018
Last Update Posted Date July 23, 2019
Study Start Date  ICMJE May 2007
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 18, 2018)
Overall Survival [ Time Frame: 7 years ]
Time from date of randomization to the date of death of any causes, or censored at last known alive date.
Original Primary Outcome Measures  ICMJE
 (submitted: June 4, 2007)
Overall Survival
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 18, 2018)
  • Progression-free Survival [ Time Frame: 7 years ]
    Time from date of randomization to the date of disease progression or death whichever came first, or censored at last disease assessment date.
  • Adverse Events [ Time Frame: 7 years ]
    Evaluated according to CTCAE V3.0
  • Methylation Status of the O6-methylguanine-DNA Methyltransferase Promoter [ Time Frame: 7 years ]
    Overall survival for patients by Methylation status of the O6-methylguanine-DNA methyltransferase promoter
Original Secondary Outcome Measures  ICMJE
 (submitted: June 4, 2007)
  • Progression-free Survival
  • Adverse Events
  • Quality of life
  • Methylation Status of the O6-methylguanine-DNA Methyltransferase Promoter
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Radiation Therapy With or Without Temozolomide in Treating Older Patients With Newly Diagnosed Glioblastoma Multiforme
Official Title  ICMJE 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
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. 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.

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 1-25.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Brain and Central Nervous System Tumors
Intervention  ICMJE
  • 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, and then adjuvantly for up to 12 cycles (150 mg/m2 for the first 5 days of each cycle). Adjuvant TMZ may be escalated to 200mg/m2 in C2 onward if appropriate.
  • 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
Study Arms  ICMJE
  • Active Comparator: Temozolomide
    Temozolomide and short course radiation
    Interventions:
    • Drug: temozolomide
    • Genetic: DNA methylation analysis
    • Procedure: quality-of-life assessment
  • Active Comparator: Radiation
    Short course radiation alone
    Interventions:
    • Genetic: DNA methylation analysis
    • Procedure: quality-of-life assessment
    • Radiation: Radiation
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 10, 2013)
562
Original Enrollment  ICMJE
 (submitted: June 4, 2007)
560
Actual Study Completion Date  ICMJE August 2016
Actual Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years to 120 Years   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Germany,   Japan,   Netherlands
Removed Location Countries Australia,   Italy
 
Administrative Information
NCT Number  ICMJE NCT00482677
Other Study ID Numbers  ICMJE CE6
CAN-NCIC-CE6 ( Registry Identifier: NCI US - Physician Data Query )
EORTC-26062-22061
TROG 08.02 ( Other Identifier: Trans-Tasman Radiation Oncology Group )
SPRI-CAN-NCIC-CE.6
CDR0000547163 ( Other Identifier: PDQ )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Canadian Cancer Trials Group
Study Sponsor  ICMJE Canadian Cancer Trials Group
Collaborators  ICMJE
  • European Organisation for Research and Treatment of Cancer - EORTC
  • Trans-Tasman Radiation Oncology Group (TROG)
Investigators  ICMJE
Study Chair: Normand Laperriere, MD, FRCPC Princess Margaret Hospital, Canada
Study Chair: James R. Perry, MD, FRCPC Toronto Sunnybrook Regional Cancer Centre
Study Chair: Alba A. Brandes, MD Ospedale Bellaria
Study Chair: Johan Menten, MD, PhD University Hospital, Gasthuisberg
PRS Account Canadian Cancer Trials Group
Verification Date April 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP