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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

Phase 2
18 Years
75 Years
Not Enrolling
Anaplastic Glioma of Brain, Loss of Chromosomes 1p/19q

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Trial Information

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

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

Inclusion Criteria

Inclusion criteria:

- Newly diagnosed histologically proven supratentorial anaplastic gliomas.The
histological diagnosis must be obtained from a neurosurgical resection or biopsy of a
tumor including an open biopsy or stereotactic biopsy.

- Absence of chromosome 1p/19q co-deletion

- Age 18 years

- Eastern Cooperative Oncology Group performance status of 0-1

- Stable or decreasing dose of steroids for 5 days prior to randomization

- Meets 1 of the following RPA classifications:class III-V

- Adequate hematologic, renal, and hepatic function

- Written informed consent

Exclusion criteria:

- Prior chemotherapy within last 5 years

- Prior radiotherapy of the head and neck area

- Receiving concurrent investigational agents or has received an investigational agent
within 30 days prior to randomization

- Planned surgery for other diseases (e.g. dental extraction)

- History of malignancy. Subjects with curatively treated cervical carcinoma in situ or
basal cell carcinoma of the skin, or subjects who have been free of other
malignancies for 5 years are eligible for this study

- Pregnant or lactating women

- Subject who disagree to follow acceptable methods of contraception

- Concurrent illness including unstable heart disease despite appropriate treatment,
history of myocardial infarction within 6 months, serious neurological or
psychological disease, and uncontrolled infection

- Subject unable to undergo Gd-MRI

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

2-year progression free survival(PFS)

Outcome Description:

Final primary end-point: 2 year PFS. Progression free survival(PFS) is defined as the time from randomization to progressive disease or death, which ever occurs earlier.

Outcome Time Frame:

Assessed and followed for the duration of hospital stay, an expected average of 3 months

Safety Issue:


Principal Investigator

Jeong Hoon Kim, Professor

Investigator Role:

Principal Investigator

Investigator Affiliation:

Asan Medical Center


Korea: Food and Drug Administration

Study ID:




Start Date:

March 2012

Completion Date:

January 2016

Related Keywords:

  • Anaplastic Glioma of Brain
  • Loss of Chromosomes 1p/19q
  • Glioma