Trial Information

Phase III Intergroup Study of Radiotherapy Versus Temozolomide Alone Versus Radiotherapy With Concomitant and Adjuvant Temozolomide for Patients With 1p/ 19q Codeleted Anaplastic Glioma

OBJECTIVES:

Primary

- Determine whether there is a survival advantage for patients with newly diagnosed
1p/19q codeleted anaplastic glioma who receive concurrent temozolomide and radiotherapy
(RT) followed by adjuvant temozolomide over that observed in patients treated with RT
alone (control).

Secondary

- Determine whether there is a neurocognitive advantage in patients who receive
temozolomide alone (Arm III) vs temozolomide with concurrent RT (Arm II) over that
observed in patients treated with RT alone (Arm I).

- Determine whether there is a difference in survival based on t(1;19)(q10,p10)
translocation status and MGMT promoter hypermethylation status in these patients.

- Perform descriptive comparisons of additional secondary outcome endpoints, including
time to progression, progression free survival, and the proportion of patients free of
progression at 6, 12, and 24 months.

- Determine the toxicity of RT and concurrent/adjuvant temozolomide in these patients.

- Determine descriptively whether it is reasonable to delay RT by documenting the time to
progression and progression-free survival of patients receiving temozolomide alone.

- Determine the quality of life and neurocognitive effects in patients treated on this
protocol and correlate these results with outcome endpoints.

- Bank blood products (i.e., plasma, DNA, and buffy coat) and tumor tissue for future
scientific investigations.

OUTLINE: This is a multicenter study. 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 status (0-1 vs 2). Patients are randomized to 1 of 3 treatment
arms.

- Arm I: Patients undergo radiotherapy (RT) 5 days a week for 6 weeks in the absence of
disease progression or unacceptable toxicity.

- Arm II: Patients undergo RT as in arm I and receive oral temozolomide once daily on
days 1-7 for 6 weeks. Beginning 4 weeks after completion of concurrent
chemoradiotherapy, patients receive adjuvant oral temozolomide once daily days 1-5.
Treatment with adjuvant temozolomide repeats every 28 days for 6-12 courses in the
absence of disease progression and unacceptable toxicity.

- Arm III: Patients receive oral temozolomide once daily on days 1-5. Treatment repeats
every 28 days for 12 courses in the absence of disease progression or unacceptable
toxicity.

Patients complete neurocognitive questionnaires (i.e., the Hopkins Verbal Learning test, the
Controlled Oral Word Association test from the Multilingual Aphasia Examination, General
Mental Ability: Trail Making tests A and B, and the Recall and Recognition of Word List
encoded from the HVLT-R test) and quality of life questionnaires (i.e., EORTC QOL-C30 and
QOL-BN20) at baseline and periodically during study therapy.

Tumor tissue samples are collected during surgery and analyzed by FISH to detect t(1:19),
and for MGMT gene promoter hypermethylation status and additional known prognostic markers,
including but not limited to PTEN, EGFR, EGFRvIII, and p53.

After completion of study therapy, patients are followed periodically.