Radiation Therapy With Concomitant and Adjuvant Temozolomide or Radiation Therapy With Adjuvant PCV or Temozolomide Alone in Treating Patients With Anaplastic Glioma or Low Grade Glioma
Brain and Central Nervous System Tumors
Drug: concomitant temozolomide (TMZ)
Drug: adjuvant temozolomide (TMZ)
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase III Intergroup Study of Temozolomide Alone Versus Radiotherapy With Concomitant and Adjuvant Temozolomide Versus Radiotherapy With Adjuvant PCV Chemotherapy in Patients With 1p/19q Co-deleted Anaplastic Glioma or Low Grade Glioma|
- Progression-free survival [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ]
- Objective tumor response [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ]
- Treatment-related adverse event as per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: Yes ]
- Time to progression (eg, clinical progression, radiographic progression or neurocognitive progression) [ Time Frame: Up to 5 years post-treatment ] [ Designated as safety issue: No ]
|Study Start Date:||September 2009|
|Estimated Primary Completion Date:||December 2018 (Final data collection date for primary outcome measure)|
Active Comparator: Arm A - Radiotherapy followed by PCV
Patients undergo radiotherapy (RT) 5 days per week for approximately 6-7 weeks. Patients receive a 4-week rest period. Patients receive PCV chemotherapy for 6 cycles and each cycle is about 6-7 weeks.
approximately for 6-7 weeksDrug: procarbazine
60 mg/m^2, oral administration days 8-21, for approximately 42 weeksDrug: CCNU
110 mg/m^2, oral administration on day 1 only for about 42 weeksDrug: vincristine
1.4 mg/m^2 IV administration on days 8 and 29 for about 42 weeks
Active Comparator: Arm B - Radiotherapy + TMZ followed by TMZ
Patients undergo radiotherapy (RT) and temozolomide (TMZ) treatment for 5 days per week for approximately 6-7 weeks. Patients receive a 4-week rest period. Patients receive temozolomide (TMZ) for 6 cycles and each cycle is about 4 weeks. Adjuvant cycles of temozolomide may be extended to 12 cycles at the physician's discretion.
Drug: concomitant temozolomide (TMZ)
75 mg/m^2, oral administration daily for approximately 6 weeksRadiation: radiotherapy
approximately for 6-7 weeksDrug: adjuvant temozolomide (TMZ)
150 or 200 mg/m^2, oral administration for days 1-5 for about 24 weeks
This study will be a randomized phase III for patients with newly diagnosed co-deleted 1p/19q anaplastic glioma or high risk low grade glioma. The trial will only enroll patients with 1p/19q co-deletion. This study includes two arms as described in the "Arms" section. A dynamic allocation procedure will be used to allocate an equal number of patients to different arms (Arms A:B = 1:1). This procedure will balance the marginal distributions of the stratification factors among arms. The stratification factors that will be used are cooperative groups (EORTC vs. all North American groups), age (≤ 50 vs. > 50), performance score (ECOG 0-1 vs. 2), and tumor grade (anaplastic glioma vs. low grade glioma).
The primary goal is to determine whether patients who receive radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant temozolomide (RT + TMZ --> TMZ) (Arm B) have a marginally better progression free survival (PFS) as compared with patients who receive radiotherapy followed by PCV chemotherapy (RT --> PCV)(Arm A).
- Time to Progression - To determine whether patients who receive (RT + TMZ --> TMZ) have a significantly longer time to progression (clinical or radiographic progression) as compared with patients who receive radiotherapy followed by adjuvant PCV chemotherapy (RT --> PCV).
- Correlation between exploratory biomarkers and survival - To determine whether there is a difference in survival based on t(1;19)(q10, p10) translocation status and MGMT promoter hypermethylation status.
- Descriptive Comparisons of Additional Secondary Endpoints - To perform descriptive comparisons of additional secondary outcome endpoints, including overall survival, objective tumor response, prognostic factor analysis and quality of life.
- Toxicity - To determine the toxicity of the treatment in each arm and perform descriptive comparisons.
- Neurocognitive and Quality of Life (QOL) Effects - To determine the neurocognitive and QOL effects in patients treated on this protocol and correlate these results with outcome endpoints.
- Banking of Biospecimens and Neuroimaging Studies - To store blood products (i.e., plasma, DNA and buffy coat), tumor tissue and MRI/CT images for future scientific investigations.
After completion of study therapy, patients are followed every 12 weeks for 1 year, then every 4 months for 2 years and then every 6 months until progressive disease or until the end of study participation.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00887146
|Contact: Kurt Jaeckle, MD||904-953-7102|
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|Study Chair:||Kurt Jaeckle, MD||Mayo Clinic|