Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma
|Brain and Central Nervous System Tumors||Drug: concomitant temozolomide (TMZ) Radiation: radiotherapy Drug: procarbazine Drug: adjuvant temozolomide (TMZ) Drug: CCNU Drug: vincristine||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||Phase III Intergroup Study of 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 ]
- Overall survival [ Time Frame: Up to 5 years post-treatment ]
- Objective tumor response [ Time Frame: Up to 5 years post-treatment ]
- 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 ]
- Time to progression (eg, clinical progression, radiographic progression or neurocognitive progression) [ Time Frame: Up to 5 years post-treatment ]
|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 about 6-7 weeks. (Cycle 1 is about 6 to 7 weeks)
Cycle 2 rest period is about 4 weeks.
Patients receive PCV chemotherapy for about 6-7 weeks, a total of 6 cycles.
Days 8-21: 60 mg/m^2 orallyDrug: CCNU
Day 1: 110 mg/m^2 orallyDrug: vincristine
Days 8 and 29: 1.4 mg/m^2 IV
Active Comparator: Arm B - Radiotherapy + TMZ followed by TMZ
Patients undergo radiotherapy (RT) and temozolomide (TMZ) treatment for 5 days per week for about 6-7 weeks (Cycle 1).
Cycle 2 rest period is about 4 weeks.
Patients receive adjuvant temozolomide for about 4 weeks, a total of 6 cycles. TMZ may be extended to 12 cycles if the patient shows acceptable tolerance and no evidence of progression.
Drug: concomitant temozolomide (TMZ)
75 mg/m^2, orally dailyRadiation: radiotherapy Drug: adjuvant temozolomide (TMZ)
150 or 200 mg/m^2 orally
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 treatment, 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|