Radiation Therapy With or Without Temozolomide in Treating Patients With Anaplastic Glioma
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 giving temozolomide during and/or after radiation therapy is more effective than radiation therapy alone in treating anaplastic glioma.
PURPOSE: This randomized phase III trial is studying giving temozolomide during and/or after radiation therapy to see how well it works compared to radiation therapy alone in treating patients with anaplastic glioma.
Brain and Central Nervous System Tumors
Genetic: DNA methylation analysis
Other: laboratory biomarker analysis
Procedure: adjuvant therapy
Procedure: quality-of-life assessment
Radiation: radiation therapy
|Study Design:||Allocation: Randomized
Primary Purpose: Treatment
|Official Title:||Phase III Trial on Concurrent and Adjuvant Temozolomide Chemotherapy in Non-1p/19q Deleted Anaplastic Glioma. The CATNON Intergroup Trial.|
- Overall survival as measured from the day of randomization [ Designated as safety issue: No ]
- Progression-free survival [ Designated as safety issue: No ]
- Neurological deterioration-free survival [ Designated as safety issue: No ]
- Quality of life as assessed by the EORTC Quality of Life Questionnaire (QLQ-C30) version 3 and the Brain Cancer Module-20 [ Designated as safety issue: No ]
- Toxicity as measured by CTEP Active Version of CTCAE [ Designated as safety issue: Yes ]
- Development of cognitive deterioration as measured by the Mini Mental Status Exam [ Designated as safety issue: Yes ]
|Study Start Date:||December 2007|
|Estimated Primary Completion Date:||June 2015 (Final data collection date for primary outcome measure)|
- To assess whether concurrent radiotherapy with daily temozolomide improves overall survival as compared to no daily temozolomide in patients with non-1p/19q deleted anaplastic glioma.
- To assess whether adjuvant temozolomide improves survival as compared to no adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma.
- To assess whether concurrent and adjuvant temozolomide prolongs progression-free survival and neurological deterioration-free survival in patients with non-1p/19q deleted anaplastic glioma.
- To assess the safety of concurrent and adjuvant temozolomide in patients with non-1p/19q deleted anaplastic glioma, including late effects on cognition.
- To assess the impact of concurrent and adjuvant temozolomide on the quality of life of patients with non-1p/19q deleted anaplastic glioma.
OUTLINE: This is a multicenter study. Patients are stratified according to institution, WHO performance status (0 vs > 0), age (≤ 50 vs > 50), presence of 1p LOH only (yes vs no), presence of oligodendroglial elements (yes vs no), and O6-methylguanine-DNA methyltransferase promoter methylation status (methylated vs unmethylated vs indeterminate). Patients are randomized to 1 of 4 treatment arms.
- Arm I: Patients undergo radiotherapy* once daily, 5 days a week, for 6.5 weeks (total of 33 fractions).
- Arm II: Patients undergo radiotherapy* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy).
- Arm III: Patients undergo radiotherapy* once daily, 5 days a week for 6.5 weeks (total of 33 fractions). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.
- Arm IV: Patients undergo radiotherapy* once daily, 5 days a week and receive oral temozolomide once daily for 6.5 weeks (total of 33 fractions of radiotherapy). Beginning 4 weeks after completion of radiotherapy, patients receive adjuvant oral temozolomide once daily on days 1-5. Treatment with adjuvant temozolomide repeats every 28 days for up to 12 courses.
NOTE: *Patients must begin radiotherapy within 8 days after randomization and within 7 weeks after surgery.
In all arms, treatment continues in the absence of disease progression or unacceptable toxicity.
Patients complete quality-of-life questionnaires, including QLQ-C30 version 3, BCM20, and the Mini Mental Status Exam at baseline, 4 weeks after the completion of radiotherapy, and then every 3 months for 5 years.
Tissue samples are collected at baseline for histology review, 1p/19q analysis, methylation status of the O6-methylguanine-DNA methyltransferase promoter, and isocitrate dehydrogenase mutation analysis.
After completion of study treatment, patients are followed every 3 months.
|Australia, Western Australia|
|Sir Charles Gairdner Hospital - Nedlands||Recruiting|
|Nedlands, Western Australia, Australia, 6009|
|Contact: Anna Nowak, MD 61-8-9346-3841|
|Winnipeg, Manitoba, Canada, R3E 0V9|
|Contact: David Eisenstat 204-787-1169|
|Heidelberg, Germany, 69120|
|Contact: Contact Person 49-6221-566-703|
|Daniel Den Hoed Cancer Center at Erasmus Medical Center||Recruiting|
|Rotterdam, Netherlands, 3008 AE|
|Contact: Contact Person 31-10-704-1415|
|Bristol Haematology and Oncology Centre||Recruiting|
|Bristol, England, United Kingdom, BS2 8ED|
|Contact: Contact Person 44-117-928-3074|
|Cambridge, England, United Kingdom, CB2 0QQ|
|Contact: Contact Person 44-1223-245-151|
|Gloucestershire Oncology Centre at Cheltenham General Hospital||Recruiting|
|Cheltenham, England, United Kingdom, GL53 7AN|
|Contact: Contact Person 44-8454-222-222|
|Royal Devon and Exeter Hospital||Recruiting|
|Exeter, England, United Kingdom, EX2 5DW|
|Contact: Contact Person 44-1392-411-611|
|Leeds Cancer Centre at St. James's University Hospital||Recruiting|
|Leeds, England, United Kingdom, LS9 7TF|
|Contact: Contact Person 44-113-206-6400|
|Manchester, England, United Kingdom, M20 4BX|
|Contact: Contact Person 44-845-226-3000|
|Nottingham City Hospital||Recruiting|
|Nottingham, England, United Kingdom, NG5 1PB|
|Contact: Contact Person 44-115-969-1169|
|Plymouth, England, United Kingdom, PL6 8DH|
|Contact: Contact Person 44-175-277-7111|
|Cancer Research Centre at Weston Park Hospital||Recruiting|
|Sheffield, England, United Kingdom, S10 2SJ|
|Contact: Contact Person 44-114-226-5000|
|Edinburgh Cancer Centre at Western General Hospital||Recruiting|
|Edinburgh, Scotland, United Kingdom, EH4 2XU|
|Contact: Contact Person 44-131-537-1000|
|Study Chair:||Wolfgang Wick||Universitatsklinikum Heidelberg|
|Study Chair:||Warren P. Mason, MD||Princess Margaret Hospital, Canada|
|Study Chair:||Michael A. Vogelbaum, MD, PhD||The Cleveland Clinic|
|Study Chair:||S. Erridge||Medical Research Council|
|Study Chair:||Anna Nowak, MD||Sir Charles Gairdner Hospital - Nedlands|