Protocol Summary

Protocol No.: OCR14992

Sponsor Protocol No.: N0577

Protocol Title: Radiation Therapy With Concomitant and Adjuvant Temozolomide Versus Radiation Therapy With Adjuvant PCV Chemotherapy in Patients With Anaplastic Glioma or Low Grade Glioma

Principal Investigator: Tran, David

Objective: 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 radiation with concomitant and adjuvant temozolomide versus radiation with adjuvant PCV is more effective in treating anaplastic glioma or low grade glioma.

Description: 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). Secondary Goals: 1. 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). 2. 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. 3. 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. 4. Toxicity - To determine the toxicity of the treatment in each arm and perform descriptive comparisons. 5. 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. 6. 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.

Phase: Phase III

Age Group: Adult

Age: 18 Years - N/A

Gender: All

Scope: National

Treatment:
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.
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.

Detailed Eligibility:
INCLUSION CRITERIA:
1. Ages 18 years old and older
2. Newly diagnosed and =Histological confirmation of anaplastic glioma (oligodendroglioma, mixed, or astrocytoma [WHO grade 2 or 3] or low grade glioma [WHO grade 2], as determined by pre-registration central pathology review. Note: Mixed gliomas are eligible, regardless of the degree of astrocytic or oligodendrocytic predominance, as long as the tumor is also co-deleted for 1p and 19q.
3. Patients with codeleted low grade gliomas must also be considered "high risk" by clinical criteria utilized in RTOG 9802 and must be either: age >= 40 and any surgical therapy or age 4. Tumor tissue must show co-deletion for the relevant portions of chromosomes 1p and 19q by FISH analysis, as defined by the testing laboratory.
5. Surgery (partial or gross total resection or biopsy) must be performed >= 2 weeks prior to registration. Patient must have recovered from the effects of surgery.
* Contact study team for complete eligibility details

Applicable Conditions:

  • Brain and Nervous System
  • Participation Institution:

  • UF Gainesville
  • More Information: View study listing on ClinicialTrials.gov http://www.clinicaltrials.gov/ct2/show/NCT00887146