Phase III Intergroup Study of Radiotherapy versus Temozolomide Alone versus Radiotherapy with Concomitant and Adjuvant Temozolomide for Patients with 1p/19q Co-deleted Anaplastic Glioma
Central pathology review submission:
This review is mandatory prior to registration to confirm eligibility. Patients must be willing to submit tissue samples for mandatory central pathology review submission and deletion status determination. It should be initiated as soon after surgery as possible.
1 = Radiotherapy is performed as 33 fractions of 1.8 Gy for a total dose of 59.4 Gy. One fraction is given daily five days per week for about 6 to 7 weeks. Cycle 1 is about 6 to 7 weeks long total.
2 = Cycle 2 rest period is 4 weeks long ((+-) 2 weeks) total.
3 = Cycles 3 to 8 are PCV chemotherapy, cycles are about 6 to 7 weeks long each.
Day 1: CCNU 110 mg/m2 orally;
Days 8 and 29: vincristine 1.4 mg/m2 IV;
Days 8 to 21: procarbazine 60 mg/m2 orally;
4 = Radiation therapy is performed as 33 fractions of 1.8 Gy for a total dose of 59.4 Gy. One fraction is given daily five days per week for about 6 to 7 weeks. Cycle 1 is about 6 to 7 weeks long total.
5 = Temozolomide (TMZ) is given as 75 mg/m2 orally daily; Cycle 1 is about 6 to 7 weeks long total.
6 = Cycle 2 rest period is 4 weeks long ((+-) 3 days) total.
7 = Adjuvant temozolomide (TMZ) is given as 150 or 1200 mg/m2 orally on days 1 to 5 only of each cycle. Cycles are about 4 weeks long each. TMZ may be extended to 12 cycles if the patient shows acceptable tolerance and no evidence of progression. Note: If patient does not complete optional cycles, they should proceed to observation phase until PD.
8 = Temozolomide is given as 150 or 1200 mg/m2 orally on days 1 to 5 only of each cycle. Cycles are about 4 weeks long each.
1. Age >= 18 years of age.
2. Newly diagnosed and <= 3 months from surgical diagnosis
3. Histological confirmation of anaplastic glioma (oligodendroglioma, mixed, or astrocytoma [WHO grade III]), 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.
4. Tumor is co-deleted for 1p and 19q.
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.
6. The following laboratory values obtained <= 21 days prior to registration:
* Absolute neutrophil count (ANC) >=1500 /mm3
* Platelet (PLTs) count >=100,000 / mm3
* Hemoglobin (Hgb) > 9.0 g/dL
* Total bilirubin <= 1.5 x institutional upper limit of normal (ULN)
* SGOT (AST) <= 3 x ULN
* Creatinine <= 1.5 x ULN
7. Negative serum or urine pregnancy test done <= 7 days prior to registration, for women of childbearing potential only.
8. Willing and able to complete neurocognitive testing without assistance and the QOL by themselves or with assistance (see Section 4.4).
9. ECOG performance status (PS) of 0, 1 or 2 (See Appendix I).
10. Provide informed written consent.
11. Willing to return to enrolling institution for follow-up during the Active Monitoring Phase (that is, the active treatment and observation portion) of the study)
12. Patient willing to provide tissue samples for correlative research purposes