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

NCT00482677 | Completed Phase 3 Results DMC

• 6 other identifiers: CE6CAN-NCIC-CE6EORTC-26062-22061TROG 08.02SPRI-CAN-NCIC-CE.6CDR0000547163
• Study Type: interventional
• Target: 562
• Locations: 4 countries
• Sites: 22

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.

Conditions

Brain and Central Nervous System Tumors

Keywords

adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

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

  7 years

Secondary Outcomes (3)

• Progression-free Survival

  7 years

• Adverse Events

  7 years

• Methylation Status of the O6-methylguanine-DNA Methyltransferase Promoter

  7 years

Study Arms (2)

Temozolomide

ACTIVE COMPARATOR

Temozolomide and short course radiation

Drug: temozolomide; Genetic: DNA methylation analysis; Procedure: quality-of-life assessment

Radiation

ACTIVE COMPARATOR

Short course radiation alone

Genetic: DNA methylation analysis; Procedure: quality-of-life assessment; Radiation: Radiation

Interventions

temozolomide 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.

Temozolomide

DNA methylation analysis 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

Radiation; Temozolomide

quality-of-life assessment PROCEDURE

prior to randomization until end of study

Radiation; Temozolomide

Radiation RADIATION

Short course radiotherapy

Radiation

Eligibility Criteria

• Age: 65 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• European Organisation for Research and Treatment of Cancer - EORTC: collaborator
• Trans Tasman Radiation Oncology Group: collaborator

Study Sites (22)

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

BCCA - Vancouver Island Cancer Centre

Victoria, British Columbia, V8R 6V5, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

Atlantic Health Sciences Corporation

Saint John, New Brunswick, E2L 4L2, Canada

Location

QEII Health Sciences Centre

Halifax, Nova Scotia, B3H 1V7, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM - Hopital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Centre hospitalier regional de Trois-Rivieres

Trois-Rivières, Quebec, G8Z 3R9, Canada

Location

Klinikum Der J.W. Goethe Universitaet

Frankfurt, 60590, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitaetsklinikum Tuebingen

Tübingen, 72076, Germany

Location

Hiroshima University Hospital

Hiroshima, 734-8551, Japan

Location

Maastro - Maastricht Radiation Oncology

Maastricht, 6201, Netherlands

Location

Related Publications (3)

• 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.

  PMID: 28296618 RESULT

• 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.

  PMID: 32632894 DERIVED

• 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.

  PMID: 24117272 DERIVED

MeSH Terms

Conditions

Central Nervous System Neoplasms; Glioblastoma; Gliosarcoma

Interventions

Temozolomide; DNA Methylation; Radiation

Condition Hierarchy (Ancestors)

Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena; Physical Phenomena

Results Point of Contact

• Title: Keyue Ding
• Organization: Canadian Cancer Trials Group

kding@ctg.queensu.ca

613-5336430

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2007
• First Posted: June 5, 2007
• Study Start: November 14, 2007
• Primary Completion: March 1, 2016
• Study Completion: August 10, 2016
• Last Updated: August 22, 2023
• Results First Posted: January 23, 2018

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

JP (1); DE (4); CA (16); NL (1)