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

Brain and Central Nervous System Tumors Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00482677
• Other study ID #: CE6
• Secondary ID: CAN-NCIC-CE6EORT
• Status: Completed
• Phase: Phase 3
• Start date: November 14, 2007
• Est. completion date: August 10, 2016

Study information

• Verified date: April 2020
• Source: Canadian Cancer Trials Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Other known NCT identifiers

• NCT00493207

Recruitment information / eligibility

• Status: Completed
• Enrollment: 562
• Est. completion date: August 10, 2016
• Est. primary completion date: March 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 120 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Glioblastoma
• Nervous System Neoplasms

Intervention

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

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre	Calgary	Alberta
Canada	Cross Cancer Institute	Edmonton	Alberta
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	CHUM - Hopital Notre-Dame	Montreal	Quebec
Canada	McGill University - Dept. Oncology	Montreal	Quebec
Canada	Atlantic Health Sciences Corporation	Saint John	New Brunswick
Canada	Centre hospitalier universitaire de Sherbrooke	Sherbrooke	Quebec
Canada	BCCA - Fraser Valley Cancer Centre	Surrey	British Columbia
Canada	Odette Cancer Centre	Toronto	Ontario
Canada	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario
Canada	Centre hospitalier regional de Trois-Rivieres	Trois-Rivieres	Quebec
Canada	BCCA - Vancouver Cancer Centre	Vancouver	British Columbia
Canada	BCCA - Vancouver Island Cancer Centre	Victoria	British Columbia
Canada	CancerCare Manitoba	Winnipeg	Manitoba
Germany	Klinikum Der J.W. Goethe Universitaet	Frankfurt
Germany	Universitaetsklinikum Freiburg	Freiburg
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Universitaetsklinikum Tuebingen	Tuebingen
Japan	Hiroshima University Hospital	Hiroshima
Netherlands	Maastro - Maastricht Radiation Oncology	Maastricht

Sponsors (3)

Lead Sponsor	Collaborator
Canadian Cancer Trials Group	European Organisation for Research and Treatment of Cancer - EORTC, Trans Tasman Radiation Oncology Group

Countries where clinical trial is conducted

Canada,  Germany,  Japan,  Netherlands, 

References & Publications (1)

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, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	7 years
Secondary	Adverse Events	Evaluated according to CTCAE V3.0	7 years
Secondary	Methylation Status of the O6-methylguanine-DNA Methyltransferase Promoter	Overall survival for patients by Methylation status of the O6-methylguanine-DNA methyltransferase promoter	7 years