N0577 (CODEL): 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

Study ID
STU 052013-059

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

Contact
Penny Currykosky
214/648-2645
penny.currykosky@utsouthwestern.edu

Principal Investigator
Edward Pan

Summary

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 (see Section 17.2) and deletion status determination. it should be initiated as soon after surgery as possible.

Randomization:
arm a
1 [?] For anaplastic glioma: 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. For low grade glioma, radiotherapy is performed as 28 fractions of 1.8 Gy for a total dose of 50.4 for approximately 6 weeks.
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

arm B
4 [?] For anaplastic glioma: 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. For low grade glioma, radiotherapy is performed as 28 fractions of 1.8 Gy for a total dose of 50.4 for approximately 6 weeks.
5 [?] For patients with anaplastic glioma, Temozolomide (TMZ) is given as 75 mg/m2 orally daily; Cycle 1 is about 6 to 7 weeks long. For patients with low grade glioma, cycle 1 is days 1 to 42.
6 [?] Cycle 2 rest period is 4 weeks long ((+-) 3 days) total.
7 [?] adjuvant temozolomide (TMZ) is given as 150 or 200 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.

Participant Eligibility

1. Age >= 18 years of age.
2. Newly diagnosed and <= 3 months from surgical diagnosis
3. Histological confirmation of anaplastic glioma or low grade glioma. Histological confirmation of anaplastic glioma or low grade glioma
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.
4. 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

* Age < 40 and subtotal resection or biopsy
5. Tumor tissue must show co-deletetion for the relevant portions of chromosomes 1p and 19q by FISH analysis, as defined by the testing laboratory.
6. 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.
7. 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
8. Negative serum or urine pregnancy test done <= 7 days prior to registration, for women of childbearing potential only.
9. Willing and able to complete neurocognitive testing without assistance and the QOL by themselves or with assistance
10. ECOG performance status (PS) of 0, 1 or 2
11. Provide informed written consent.
12. 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)
13. Patient willing to provide tissue samples for correlative research purposes

Inclusion of Women and Minorities
Both men and women of all races and ethnic groups are eligible for this study.