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Radiation Therapy With or Without Temozolomide in Treating Patients With Low-Grade Glioma

Phase 3
Active, not recruiting
Conditions
Neurotoxicity
Brain and Central Nervous System Tumors
Interventions
Radiation: 3-dimensional conformal radiation therapy
Radiation: intensity-modulated radiation therapy
Registration Number
NCT00978458
Lead Sponsor
Eastern Cooperative Oncology Group
Brief Summary

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether radiation therapy is more effective when given together with or without temozolomide in treating patients with low-grade glioma.

PURPOSE: This randomized phase III trial is studying radiation therapy so see how well it works when given together with or without temozolomide in treating patients with low-grade glioma.

Detailed Description

OBJECTIVES:

Primary

* 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.

Secondary

* 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 temozolomide.

* 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 years.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
540
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm I3-dimensional conformal radiation therapyPatients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).
Arm Iintensity-modulated radiation therapyPatients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).
Arm IIintensity-modulated radiation therapyPatients 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.
Arm II3-dimensional conformal radiation therapyPatients 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.
Arm IItemozolomidePatients 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.
Primary Outcome Measures
NameTimeMethod
Progression-free survival (PFS)
Overall survival (OS)
Secondary Outcome Measures
NameTimeMethod
Neurocognitive functioning as assessed at baseline, annually until disease progression, and at the time of disease progression
Quality of life as assessed by the FACT-BR questionnaire at baseline, annually until disease progression, and at the time of disease progression
Correlation of pre-treatment 1p and 19q levels in tumor tissue samples with PFS and OS

Trial Locations

Locations (168)

UAB Comprehensive Cancer Center

🇺🇸

Birmingham, Alabama, United States

Arizona Oncology Services Foundation

🇺🇸

Phoenix, Arizona, United States

Rebecca and John Moores UCSD Cancer Center

🇺🇸

La Jolla, California, United States

Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

🇺🇸

Orange, California, United States

Aurora Presbyterian Hospital

🇺🇸

Aurora, Colorado, United States

St. Anthony Central Hospital

🇺🇸

Denver, Colorado, United States

Porter Adventist Hospital

🇺🇸

Denver, Colorado, United States

Presbyterian - St. Luke's Medical Center

🇺🇸

Denver, Colorado, United States

St. Joseph Hospital

🇺🇸

Denver, Colorado, United States

CCOP - Colorado Cancer Research Program

🇺🇸

Denver, Colorado, United States

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UAB Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States
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