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

NCT ID: NCT00482677

Last Updated: 2023-08-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 562 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-14
• Study Completion Date: 2016-08-10

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Temozolomide

Temozolomide and short course radiation

Group Type: ACTIVE_COMPARATOR

temozolomide

Intervention Type: DRUG

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 analysis

Intervention Type: GENETIC

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 assessment

Intervention Type: PROCEDURE

prior to randomization until end of study

Radiation

Short course radiation alone

Group Type: ACTIVE_COMPARATOR

DNA methylation analysis

Intervention Type: GENETIC

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 assessment

Intervention Type: PROCEDURE

prior to randomization until end of study

Radiation

Intervention Type: RADIATION

Short course radiotherapy

Interventions

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.

Intervention Type: DRUG

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

Intervention Type: GENETIC

quality-of-life assessment

prior to randomization until end of study

Intervention Type: PROCEDURE

Radiation

Short course radiotherapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: collaborator

Trans Tasman Radiation Oncology Group

OTHER

Sponsor Role: collaborator

Canadian Cancer Trials Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Normand Laperriere, MD, FRCPC

Role: STUDY_CHAIR

Princess Margaret Hospital, Canada

James R. Perry, MD, FRCPC

Role: STUDY_CHAIR

Toronto Sunnybrook Regional Cancer Centre

Alba A. Brandes, MD

Role: STUDY_CHAIR

Ospedale Bellaria

Johan Menten, MD, PhD

Role: STUDY_CHAIR

University Hospital, Gasthuisberg

Locations

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Cross Cancer Institute

Edmonton, Alberta, Canada

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, Canada

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, Canada

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Atlantic Health Sciences Corporation

Saint John, New Brunswick, Canada

QEII Health Sciences Centre

Halifax, Nova Scotia, Canada

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, Canada

London Regional Cancer Program

London, Ontario, Canada

Odette Cancer Centre

Toronto, Ontario, Canada

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, Canada

CHUM - Hopital Notre-Dame

Montreal, Quebec, Canada

McGill University - Dept. Oncology

Montreal, Quebec, Canada

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, Canada

Centre hospitalier regional de Trois-Rivieres

Trois-Rivières, Quebec, Canada

Klinikum Der J.W. Goethe Universitaet

Frankfurt, , Germany

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitaetsklinikum Leipzig

Leipzig, , Germany

Universitaetsklinikum Tuebingen

Tübingen, , Germany

Hiroshima University Hospital

Hiroshima, , Japan

Maastro - Maastricht Radiation Oncology

Maastricht, , Netherlands

Countries

Canada; Germany; Japan; Netherlands

References

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.

Reference Type: RESULT

PMID: 28296618 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32632894 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24117272 (View on PubMed)

Other Identifiers

CAN-NCIC-CE6

Identifier Type: REGISTRY

Identifier Source: secondary_id

EORTC-26062-22061

Identifier Type: OTHER

Identifier Source: secondary_id

TROG 08.02

Identifier Type: OTHER

Identifier Source: secondary_id

SPRI-CAN-NCIC-CE.6

Identifier Type: -

Identifier Source: secondary_id

CDR0000547163

Identifier Type: OTHER

Identifier Source: secondary_id

CE6

Identifier Type: -

Identifier Source: org_study_id

NCT00493207

Identifier Type: -

Identifier Source: nct_alias