Radiation Therapy With or Without Temozolomide in Treating Older Patients With Newly Diagnosed Glioblastoma Multiforme
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| ClinicalTrials.gov Identifier: NCT00482677 |
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Recruitment Status :
Completed
First Posted : June 5, 2007
Results First Posted : January 23, 2018
Last Update Posted : April 9, 2020
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Brain and Central Nervous System Tumors | Drug: temozolomide Genetic: DNA methylation analysis Procedure: quality-of-life assessment Radiation: Radiation | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 562 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| 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 |
| Actual Study Start Date : | May 1, 2007 |
| Actual Primary Completion Date : | March 1, 2016 |
| Actual Study Completion Date : | August 10, 2016 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Temozolomide
Temozolomide and short course radiation
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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 |
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Active Comparator: Radiation
Short course radiation alone
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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 |
- Overall Survival [ Time Frame: 7 years ]Time from date of randomization to the date of death of any causes, or censored at last known alive date.
- Progression-free Survival [ Time Frame: 7 years ]Time from date of randomization to the date of disease progression or death whichever came first, or censored at last disease assessment date.
- Adverse Events [ Time Frame: 7 years ]Evaluated according to CTCAE V3.0
- Methylation Status of the O6-methylguanine-DNA Methyltransferase Promoter [ Time Frame: 7 years ]Overall survival for patients by Methylation status of the O6-methylguanine-DNA methyltransferase promoter
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 65 Years to 120 Years (Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00482677
Show 22 study locations
| Study Chair: | 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 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Canadian Cancer Trials Group |
| ClinicalTrials.gov Identifier: | NCT00482677 |
| Obsolete Identifiers: | NCT00493207 |
| Other Study ID Numbers: |
CE6 CAN-NCIC-CE6 ( Registry Identifier: NCI US - Physician Data Query ) EORTC-26062-22061 ( Other Identifier: EORTC ) TROG 08.02 ( Other Identifier: Trans-Tasman Radiation Oncology Group ) SPRI-CAN-NCIC-CE.6 CDR0000547163 ( Other Identifier: PDQ ) |
| First Posted: | June 5, 2007 Key Record Dates |
| Results First Posted: | January 23, 2018 |
| Last Update Posted: | April 9, 2020 |
| Last Verified: | April 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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adult glioblastoma adult giant cell glioblastoma adult gliosarcoma |
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Glioblastoma Nervous System Neoplasms Central Nervous System Neoplasms Astrocytoma Glioma Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms |
Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Neoplasms by Site Nervous System Diseases Temozolomide Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents |