Clinical trial NCT00482677: Radiation Therapy With or Without Temozolomide in Treating Older Patients With Newly Diagnosed Glioblastoma Multiforme
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
Collaborators: name: European Organisation for Research and Treatment of Cancer - EORTC
name: Trans Tasman Radiation Oncology Group
First posted: 2007-06-05
Enrollment: 562
Sex: ALL
Minimum age (years): 65
Maximum age (years): 120
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall Survival
timeFrame: 7 years
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 7 years
measure: Adverse Events
timeFrame: 7 years
measure: Methylation Status of the O6-methylguanine-DNA Methyltransferase Promoter
timeFrame: 7 years
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Surrey
country: Canada
facility: BCCA - Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Victoria
country: Canada
facility: BCCA - Vancouver Island Cancer Centre
state: British Columbia
city: Winnipeg
country: Canada
facility: CancerCare Manitoba
state: Manitoba
city: Saint John
country: Canada
facility: Atlantic Health Sciences Corporation
state: New Brunswick
city: Halifax
country: Canada
facility: QEII Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Juravinski Cancer Centre at Hamilton Health Sciences
state: Ontario
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Toronto
country: Canada
facility: Odette Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM - Hopital Notre-Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University - Dept. Oncology
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre hospitalier universitaire de Sherbrooke
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Centre hospitalier regional de Trois-Rivieres
state: Quebec
city: Frankfurt
country: Germany
facility: Klinikum Der J.W. Goethe Universitaet
city: Freiburg
country: Germany
facility: Universitaetsklinikum Freiburg
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Tuebingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Maastricht
country: Netherlands
facility: Maastro - Maastricht Radiation Oncology
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Normand Laperriere, MD, FRCPC
role: STUDY_CHAIR
affiliation: Toronto Sunnybrook Regional Cancer Centre
name: James R. Perry, MD, FRCPC
role: STUDY_CHAIR
affiliation: Ospedale Bellaria
name: Alba A. Brandes, MD
role: STUDY_CHAIR
affiliation: University Hospital, Gasthuisberg
name: Johan Menten, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.