Overview

This trial is active, not recruiting.

Condition brain and central nervous system tumors
Treatments temozolomide, dna methylation analysis, quality-of-life assessment, radiation
Phase phase 3
Sponsor Canadian Cancer Trials Group
Collaborator European Organisation for Research and Treatment of Cancer - EORTC
Start date May 2007
End date March 2016
Trial size 562 participants
Trial identifier NCT00482677, CAN-NCIC-CE6, CDR0000547163, CE6, EORTC-26062-22061, NCT00493207, SPRI-CAN-NCIC-CE.6, TROG 08.02

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Active Comparator)
Temozolomide and short course radiation
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.
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
quality-of-life assessment
prior to randomization until end of study
(Active Comparator)
Short course radiation alone
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
quality-of-life assessment
prior to randomization until end of study
radiation
Short course radiotherapy

Primary Outcomes

Measure
Overall survival
time frame: 7 years

Secondary Outcomes

Measure
Progression-free survival
time frame: 7 years
Adverse events
time frame: 7 years
Quality of life
time frame: 7 years
Methylation status of the O6-methylguanine-DNA methyltransferase promoter
time frame: 7 years

Eligibility Criteria

Male or female participants from 65 years up to 120 years old.

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

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Canadian Cancer Trials Group.