Radiation Therapy With Concomitant and Adjuvant Temozolomide or Radiation Therapy With Adjuvant PCV or Temozolomide Alone in Treating Patients With Anaplastic Glioma
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. It is not yet known whether giving temozolomide alone, radiation followed by PCV, or temozolomide together with radiation therapy followed by temozolomide is more effective in treating anaplastic glioma.
Brain and Central Nervous System Tumors
Drug: Temozolomide (TMZ)
Drug: PCV - Procarbazine + CCNU + Vincristine
|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|
- Progression-free survival [ Time Frame: Up to 2 years post-registration ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: No ]
- Time to progression (i.e., clinical progression, neurocognitive progression, and radiographic progression) [ Time Frame: Up to 2 years post-registration ] [ Designated as safety issue: No ]
- Objective tumor response [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: No ]
- Treatment-related adverse events according to NCI CTCAE v. 3 [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 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 in Cycle 1. The patient undergoes a rest period for approximately 4 weeks in Cycle 2. For Cycles 3-8, patients are administered PCV chemotherapy for about 6 - 7 weeks for each cycle in the absence of disease progression and unacceptable toxicity.
Patients undergo radiotherapy performed as 33 fractions of 1.8 Gy for a total dose of 59.4 Gy.Drug: PCV - Procarbazine + CCNU + Vincristine
Patients receive PCV chemotherapy. On Day 1, CCNU 110 mg/m2 is administered orally. On Days 8 and 29, vincristine 1.4 mg/m2 is administered intravenously. And on Days 8-21, procarbazine 60 mg/m2 is administered orally. The course of treatment is repeated for a total of 6 cycles.
Experimental: Arm B - Radiotherapy + TMZ followed by TMZ
Patients undergo radiation and temozolomide treatment daily for Cycle 1 for approximately 6-7 weeks. Patients receive temozolomide 75 mg/m2 orally. There is a rest period for approximately 4 weeks during Cycle 2. For Cycles 3-8, patients undergo adjuvant temozolomide 150 or 1200 mg/m2 orally on Days 1-5 of each cycle. Each cycle is approximately 4 weeks in duration. Temozolomide may be extended to 12 cycles if there is acceptable tolerance and no evidence of progression.
Drug: Temozolomide (TMZ)
Patients receive oral temozolomide.Radiation: Radiotherapy
Patients undergo radiotherapy performed as 33 fractions of 1.8 Gy for a total dose of 59.4 Gy.
Experimental: Arm C - TMZ
Patients receive oral temozolomide 150 or 1200 mg/m2 once daily on days 1-5 of each cycle. Each cycle is approximately 4 weeks. Patients undergo treatment for a total of 12 cycles in the absence of disease progression or unacceptable toxicity.
Drug: Temozolomide (TMZ)
Patients receive oral temozolomide.
This research study is a Phase III clinical trial. The purpose of this study is to compare the effectiveness of radiotherapy with temozolomide followed by temozolomide chemotherapy versus radiotherapy followed by PCV chemotherapy versus temozolomide chemotherapy alone in the treatment of anaplastic glioma. Patients are stratified according to cooperative group (EORTC vs North American groups [NCCTG, RTOG, CTSU, and NCIC CTG]), age (≤ 50 years vs > 50 years), and ECOG performance score (0 or 1 vs 2). Patients are randomized to 1 of 3 treatment arms. Please see the "Arms" section below for more detailed information. The primary and secondary objectives are summarized below.
To determine whether patients who receive radiotherapy with concomitant temozolomide (TMZ) followed by adjuvant temozolomide (RT + TMZ --> TMZ) have a marginally better progression free survival (PFS) than patients who receive radiotherapy followed by PCV chemotherapy (RT --> PCV).
- Time to Progression - To determine whether patients who receive temozolomide (TMZ) alone have a significantly longer time to progression (neurocognitive, clinical or radiographic progression) than patients who receive radiotherapy with concomitant TMZ followed by adjuvant TMZ (RT + TMZ --> TMZ) or radiotherapy followed by PCV chemotherapy (RT --> PCV).
- Survival Difference - Determine whether there is a difference in survival based on translocation status and MGMT promoter hypermethylation status.
- Descriptive Comparisons of Additional Secondary Endpoints - Perform descriptive comparisons of additional secondary outcome endpoints, including overall survival, objective tumor response, prognostic factor analysis and quality of life.
- Toxicity - Determine the toxicity of the treatment in each arm and perform descriptive comparisons.
- Descriptive Determination of Timing of RT - Determine descriptively whether it is reasonable to delay RT in this patient cohort by documenting the time to progression and progression free survival of patients receiving temozolomide alone
- Neurocognitive and Quality of Life (QOL) Effects - Determine the neurocognitive and QOL effects in patients treated on this protocol and correlate these results with outcome endpoints
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.
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|Study Chair:||Kurt A. Jaeckle, MD||Mayo Clinic|