Radiation Therapy With Concomitant and Adjuvant Temozolomide or Radiation Therapy With Adjuvant PCV or Temozolomide Alone in Treating Patients With Anaplastic Glioma
Brain and Central Nervous System Tumors
Drug: 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|
- 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 ]
- Objective tumor response [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: No ]
- Treatment-related adverse event [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: Yes ]
- Time to progression (eg, clinical progression, radiographic progression or neurocognitive progression) [ Time Frame: Up to 5 years post-registration ] [ 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. The patient has a 4-6 week treatment break. Patients receive PCV chemotherapy for 6 cycles of six to seven week-long cycles. During each cycle of PCV chemotherapy, the patient receives the three medications that compose PCV chemotherapy as follows:
59.4 GyDrug: PCV
CCNU (oral), vincristine (IV) and procarbazine (oral)
Active Comparator: Arm B - Radiotherapy + TMZ followed by TMZ
Patients receive radiotherapy five days per week. Radiation therapy is performed as 33 fractions of 1.8 Gy for a total dose of 59.4 Gy. Temozolomide is given as 75 mg/m^2 orally daily during Cycle 1 for seven days per week for about 6-7 weeks. Patients have a 4 week treatment break. Adjuvant temozolomide is given as 150 or 200 mg/m^2 orally on days 1-5 only of each cycle. Cycles are about 4 weeks long each. Temozolomide may be extended to 12 cycles if the patients shows acceptable tolerance and no evidence of progression.
Drug: temozolomide (TMZ)
Experimental: Arm C - TMZ Alone
Patients receive temozolomide 150 or 200 mg/m^2 orally on days 1-5 only for each cycle. Cycles are about 4 weeks long each.
Drug: temozolomide (TMZ)
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, 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 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
- Banking of Biospecimens To bank 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
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|Study Chair:||Kurt A. Jaeckle, MD||Mayo Clinic|