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Phase III Study of Radiation Therapy With or Without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas

Phase 3
18 Years
Open (Enrolling)
Brain and Central Nervous System Tumors, Neurotoxicity

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Trial Information

Phase III Study of Radiation Therapy With or Without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas



- To determine whether the addition of temozolomide to fractionated radiotherapy improves
the progression-free survival (PFS) of patients with symptomatic or progressive
low-grade gliomas.

- To determine whether the addition of temozolomide to fractionated radiotherapy improves
the median overall survival (OS) of these patients.


- To determine whether combination therapy with temozolomide and radiotherapy improves or
maintains cognition and quality of life compared to radiotherapy alone.

- To compare the toxicities (severe or worse [≥ grade 3]) of radiotherapy with vs without
temozolomide in these patients.

- To assess the impact of the presence or absence of 1p and 19q deletion on PFS and OS.

- To determine the impact of 1p and 19q status on PFS and OS of patients treated with

- To create a tumor and tissue bank, including plasma and germ line DNA, within the ECOG
Pathology Coordinating Office.

OUTLINE: This is a multicenter study. Patients are stratified according to age (< 40 years
vs ≥ 40 years), 1p and 19q status (both deleted vs either/both intact vs undeterminable),
pre-operative maximum tumor diameter (< 6 cm vs ≥ 6 cm [based on T2 or FLAIR MRI]),
Karnofsky performance status (60-70% vs 80-100%), and contrast enhancement on pre-treatment
MRI scan (present vs absent). Patients are randomized to 1 of 2 treatment arms.

- Arm I: Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy
once daily 5 days a week for 5½ weeks (28 fractions).

- Arm II: Patients undergo radiotherapy as in arm I and receive concurrent oral
temozolomide once daily for 5½ weeks. Beginning 28 days after completion of
chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5.
Treatment with temozolomide repeats every 28 days for 12 courses in the absence of
disease progression or unacceptable toxicity.

Some patients undergo quality-of-life and neurocognitive (e.g., visual scanning speed,
divided attention, language, memory, and fine motor skills) assessments at baseline,
annually until disease progression, and at the time of disease progression.

Tumor tissue samples are collected at baseline for confirmation of diagnosis and
determination of 1p and 19q deletion status. Peripheral blood, serum, and additional tumor
tissue samples may be collected for further research studies.

After completion of study treatment, patients are followed up periodically for up to 15

Inclusion Criteria


- Histologically confirmed* supratentorial low-grade glioma, including 1 of the

- Grade 2 astrocytoma

- Grade 2 oligodendroglioma

- Grade 2 oligoastrocytoma (mixed glioma containing astrocytoma and

- NOTE: *If the pathology from multiple procedures supports the diagnosis of a brain
tumor, the qualifying pathology of grade 2 astrocytoma, oligodendroglioma, or
oligoastrocytoma must be the most recent pathological diagnosis; no pathological
diagnosis of grade 3 or 4 glioma at any time

- Paraffin-embedded tumor specimen available for submission for confirmation of
pathological review and determination of 1p and 19q deletion status

- Patients must currently meet ≥ 1 of the following criteria*:

- Uncontrolled symptoms, defined as any of the following:

- Headaches associated with mass effect

- Uncontrolled seizures despite two different antiepileptic drug regimens
(i.e., two antiepileptic drugs tested either sequentially or in

- Focal neurological symptoms

- Cognitive symptoms or deficits

- Tumor progression by serial MRIs, defined as any of the following:

- New or progressive enhancement

- New or progressive T2 or FLAIR signal abnormality

- Age ≥ 40 years

- NOTE: *Patients < 40 years of age whose only symptom of low-grade glioma is seizures
that are well-controlled on antiepileptic drugs AND who have no evidence of
radiographic progression are not eligible.

- Patients who have undergone gross total resection and have no detectable residual
disease are eligible

- No pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, or
dysembryoplastic neuroepithelial tumors


- Karnofsky performance status 60-100%

- WBC ≥ 3,000/mm^3

- ANC ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- Hematocrit ≥ 30%

- Bilirubin ≤ 2 times upper limit of normal (ULN)

- AST and ALT ≤ 3 times ULN

- Creatinine ≤ 2.0 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Able to undergo MRI with and without contrast

- No other malignancy within the past 5 years, except for nonmelanoma skin cancer or
cervical carcinoma in situ

- No uncontrolled infection

- No known HIV positivity

- No medical disorder that would increase risks associated with radiotherapy and

- No other disorder that would limit life expectancy to < 5 years


- No prior radiotherapy, cytotoxic chemotherapy, radiosurgery, or investigational
therapy directed at the brain tumor

- Any number of prior surgical procedures for the brain tumor allowed

- No prior radiotherapy to the head unless the radiotherapy ports entirely excluded the

- At least 2 weeks since any prior brain surgery (e.g., stereotatic biopsy, open
biopsy, or resection)

- At least 6 weeks since prior MRI and chest x-ray

- If resection is performed, an MRI after surgery is required

Type of Study:


Study Design:

Allocation: Randomized, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS)

Safety Issue:


Principal Investigator

David Schiff, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of Virginia



Study ID:




Start Date:

September 2009

Completion Date:

Related Keywords:

  • Brain and Central Nervous System Tumors
  • Neurotoxicity
  • neurotoxicity
  • adult diffuse astrocytoma
  • adult oligodendroglioma
  • recurrent adult brain tumor
  • adult mixed glioma
  • Glioma
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Neurotoxicity Syndromes



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