Anaplastic Glioma of Brain Clinical Trial
Official title:
A Randomized Phase 2 Study to Evaluate the Efficacy Between Only Radiotherapy Versus CCRT With Temozolomide in Newly Diagnosed Grade III Gliomas Without 1p/19q Codeletion
1. The management of anaplastic gliomas of WHO grade 3 is currently largely based on
surgery followed by radiotherapy, of which prognosis remains still dismal with the
median survival of 2-5 years. To date, the benefit of chemo for WHO grade 3 gliomas is
unclear of modest at best with conventional cytotoxic agents, and the role of
temozolomide for these entities still is not elucidated.
2. Codeletion of chromosome 1p/19q is considered the most important marker of prognostic
significance in WHO grade 3 gliomas.
3. To project a randomized phase 2 screening trial examining the efficacy of concurrent
chemoradiotherapy with temozolomide followed by adjuvant temozolomide for WHO grade 3
gliomas without codeletion of chromosome 1p/19q.
4. The prognostic significance of methylation status of MGMT and IDH1 mutation as
molecular markers will be also assessed in each arm as key secondary analysis.
The role of chemotherapy for gliomas has been recently reappraised by the advent of
temozolomide, especially for glioblastomas, and further investigation is now being directed
to unveiling its optimal indications, dosing protocols, and the most relevant prognostic
factors. Meanwhile, the management of anaplastic gliomas of WHO grade 3 (anaplastic
astrocytomas, anaplastic oligodendrogliomas, and anaplastic oligoastrocytomas) is currently
largely based on surgery followed by radiotherapy, of which prognosis remains still dismal
with the median survival of 2-5 years. To date, the benefit of chemo for WHO grade 3 gliomas
is unclear of modest at best with conventional cytotoxic agents, and the role of
temozolomide for these entities still is not elucidated. Moreover, WHO grade 3 gliomas are
now known to consist of heterogeneous groups of different histologic features, biological
behaviors, and prognoses. Accordingly, relevant molecular markers are appreciated with the
growing body of data that showing their implications on response to therapy and survival,
including codeletion of chromosome 1p/19q, methylation status of methylguanine methyl
transferase (MGMT), and isocitrate dehydrogenase (IDH) mutation.1,4-6,11 Among those,
codeletion of chromosome 1p/19q is considered the most important marker of prognostic
significance in WHO grade 3 gliomas.
One recent Korean prospective cohort study showed the potential survival benefit and safety
of concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide for WHO
grade 3 gliomas. In this study, however, the role of molecular markers such as codeletion of
chromosome 1p/19q and MGMT methylation could not be determined because of small number of
patients available. These results prompted this Korean group to project a randomized phase 2
screening trial examining the efficacy of concurrent chemoradiotherapy with temozolomide
followed by adjuvant temozolomide for WHO grade 3 gliomas without codeletion of chromosome
1p/19q. The basic concept of the present clinical trial is "a subgroup with expected worse
prognosis according to the status of chromosome 1p/19q, i.e. one without codeletion of
chromosome 1p/19q is to be managed more aggressively", to investigate the role of
temozolomide. An aggressive therapy (surgery + concurrent chemoradiotherapy with
temozolomide followed by adjuvant temozolomide) will be compared to the conventional arm
(surgery + radiotherapy only) in terms of its efficacy and safety for WHO grade 3 gliomas
without chromosome 1p/19q codeletion. The prognostic significance of methylation status of
MGMT and IDH1 mutation as molecular markers will be also assessed in each arm as key
secondary analysis. Until now, there have been no such trials examining the efficacy and
safety of temozolomide for WHO grade 3 gliomas based on prospective molecular
stratification.
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Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
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