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Brain and Central Nervous System TumorsPhase 3NCT00482677

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

A Phase 3 study testing temozolomide, DNA methylation analysis and quality-of-life assessment in people with Brain and Central Nervous System Tumors, run by Canadian Cancer Trials Group at 22 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 65 to 120 years
Conditions the study is for
Brain and Central Nervous System Tumors
What is being tested?
temozolomide, DNA methylation analysis and quality-of-life assessment
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
562 participants
Where
22 sitesin 4 countries
Study dates
14 Nov 2007to 10 Aug 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 to 120 years
  • All sexes
  • No healthy volunteers
  • Older adult

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

Trial locations and contacts

22 sites in 4 countries.

22 sites in 4 countries

Canada16 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z2

  • QEII Health Sciences Centre

    Halifax, Nova Scotia, B3H 1V7

  • Juravinski Cancer Centre at Hamilton Health Sciences

    Hamilton, Ontario, L8V 5C2

  • London Regional Cancer Program

    London, Ontario, N6A 4L6

  • CHUM - Hopital Notre-Dame

    Montreal, Quebec, H2L 4M1

  • McGill University - Dept. Oncology

    Montreal, Quebec, H2W 1S6

  • Atlantic Health Sciences Corporation

    Saint John, New Brunswick, E2L 4L2

  • Centre hospitalier universitaire de Sherbrooke

    Sherbrooke, Quebec, J1H 5N4

  • BCCA - Fraser Valley Cancer Centre

    Surrey, British Columbia, V3V 1Z2

  • Odette Cancer Centre

    Toronto, Ontario, M4N 3M5

  • Univ. Health Network-Princess Margaret Hospital

    Toronto, Ontario, M5G 2M9

  • Centre hospitalier regional de Trois-Rivieres

    Trois-Rivières, Quebec, G8Z 3R9

  • BCCA - Vancouver Cancer Centre

    Vancouver, British Columbia, V5Z 4E6

  • BCCA - Vancouver Island Cancer Centre

    Victoria, British Columbia, V8R 6V5

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

Germany4 sites

  • Klinikum Der J.W. Goethe Universitaet

    Frankfurt, 60590

  • Universitaetsklinikum Freiburg

    Freiburg im Breisgau, 79106

  • Universitaetsklinikum Leipzig

    Leipzig, 04103

  • Universitaetsklinikum Tuebingen

    Tübingen, 72076

Other trials in Germany

Japan1 site

  • Hiroshima University Hospital

    Hiroshima, 734-8551

Other trials in Japan

Netherlands1 site

  • Maastro - Maastricht Radiation Oncology

    Maastricht, 6201

Other trials in Netherlands

About this study

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

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.

Read the 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.

Being tested
temozolomide, DNA methylation analysis, quality-of-life assessment, Radiation
Keywords
adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma
Medical subject headings
Central Nervous System Neoplasms, Glioblastoma, Gliosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • temozolomideDrug

    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.

  • DNA methylation analysisGenetic

    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

  • quality-of-life assessmentProcedure or surgery

    prior to randomization until end of study

  • RadiationRadiation

    Short course radiotherapy

Study groups in NCT00482677
Study groupRoleWhat they receive
TemozolomideActive comparatorTemozolomide and short course radiation
Receives: Drug: temozolomide; Genetic: DNA methylation analysis; Procedure: quality-of-life assessment
RadiationActive comparatorShort course radiation alone
Receives: Genetic: DNA methylation analysis; Procedure: quality-of-life assessment; Radiation: Radiation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival

    Time from date of randomization to the date of death of any causes, or censored at last known alive date.

    Measured: 7 years

Secondary outcomes (3)

  1. Progression-free Survival

    Time from date of randomization to the date of disease progression or death whichever came first, or censored at last disease assessment date.

    Measured: 7 years

  2. Adverse Events

    Evaluated according to CTCAE V3.0

    Measured: 7 years

  3. Methylation Status of the O6-methylguanine-DNA Methyltransferase Promoter

    Overall survival for patients by Methylation status of the O6-methylguanine-DNA methyltransferase promoter

    Measured: 7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jun 2007 (estimated)
  2. Study start14 Nov 2007
  3. Primary completion1 Mar 2016
  4. Study completion10 Aug 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
562 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00482677
Sponsor's protocol ID
CE6
Other IDs
CAN-NCIC-CE6, EORTC-26062-22061, TROG 08.02, SPRI-CAN-NCIC-CE.6, CDR0000547163
Status last verified
Apr 2020
First submitted
4 Jun 2007
Last updated
22 Aug 2023
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Perry JR, Laperriere N, O'Callaghan CJ, Brandes AA, Menten J, Phillips C, Fay M, Nishikawa R, Cairncross JG, Roa W, Osoba D, Rossiter JP, Sahgal A, Hirte H, Laigle-Donadey F, Franceschi E, Chinot O, Golfinopoulos V, Fariselli L, Wick A, Feuvret L, Back M, Tills M, Winch C, Baumert BG, Wick W, Ding K, Mason WP; Trial Investigators. Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma. N Engl J Med. 2017 Mar 16;376(11):1027-1037. doi: 10.1056/NEJMoa1611977.

    PubMed 28296618

  • Climans SA, Brandes AA, Cairncross JG, Ding K, Fay M, Laperriere N, Menten J, Nishikawa R, O'Callaghan CJ, Perry JR, Phillips C, Roa W, Wick W, Winch C, Mason WP. Temozolomide and seizure outcomes in a randomized clinical trial of elderly glioblastoma patients. J Neurooncol. 2020 Aug;149(1):65-71. doi: 10.1007/s11060-020-03573-x. Epub 2020 Jul 6.

    PubMed 32632894

  • Fiorentino A, De Bonis P, Chiesa S, Balducci M, Fusco V. Elderly patients with glioblastoma: the treatment challenge. Expert Rev Neurother. 2013 Oct;13(10):1099-105. doi: 10.1586/14737175.2013.840419.

    PubMed 24117272

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing temozolomide, DNA methylation analysis and quality-of-life assessment in people with Brain and Central Nervous System Tumors, run by Canadian Cancer Trials Group at 22 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Canada, Germany, Japan, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (time frame: 7 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00482677, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.

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