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

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ClinicalTrials.gov Identifier: NCT00978458

Recruitment Status : Active, not recruiting

First Posted : September 17, 2009

Last Update Posted : December 14, 2017

Sponsor:

Collaborator:

National Cancer Institute (NCI)

Information provided by (Responsible Party):

Eastern Cooperative Oncology Group

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Brain and Central Nervous System Tumors Neurotoxicity	Drug: temozolomide Radiation: 3-dimensional conformal radiation therapy Radiation: intensity-modulated radiation therapy	Phase 3

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.

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	540 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Primary Purpose:	Treatment
Official Title:	Phase III Study of Radiation Therapy With or Without Temozolomide for Symptomatic or Progressive Low-Grade Gliomas
Study Start Date :	September 2009
Estimated Primary Completion Date :	December 31, 2021
Estimated Study Completion Date :	December 31, 2026

Resource links provided by the National Library of Medicine

Drug Information available for: Temozolomide

Genetic and Rare Diseases Information Center resources: Glioma Oligodendroglioma Neurotoxicity Syndromes Brain Tumor, Adult Diffuse Astrocytoma Neuroepithelioma

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Arm I Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily 5 days a week for 5½ weeks (28 fractions).	Radiation: 3-dimensional conformal radiation therapy Given once daily 5 days a week for 5½ weeks Radiation: intensity-modulated radiation therapy Given once daily 5 days a week for 5½ weeks
Experimental: 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.	Drug: temozolomide Given orally Radiation: 3-dimensional conformal radiation therapy Given once daily 5 days a week for 5½ weeks Radiation: intensity-modulated radiation therapy Given once daily 5 days a week for 5½ weeks

Outcome Measures

Primary Outcome Measures :

Progression-free survival (PFS)
Overall survival (OS)

Secondary Outcome Measures :

Quality of life as assessed by the FACT-BR questionnaire at baseline, annually until disease progression, and at the time of disease progression
Neurocognitive functioning as assessed 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

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 120 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed* supratentorial low-grade glioma, including 1 of the following:
- Grade 2 astrocytoma
- Grade 2 oligodendroglioma
- Grade 2 oligoastrocytoma (mixed glioma containing astrocytoma and oligodendroglioma)
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 combination)
  - 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

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

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 brain
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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00978458

Show 168 Study Locations

Sponsors and Collaborators

Eastern Cooperative Oncology Group

National Cancer Institute (NCI)

Investigators


Study Chair:	David Schiff, MD	University of Virginia

More Information


Responsible Party:	Eastern Cooperative Oncology Group
ClinicalTrials.gov Identifier:	NCT00978458 History of Changes
Other Study ID Numbers:	CDR0000654697 ECOG-E3F05
First Posted:	September 17, 2009 Key Record Dates
Last Update Posted:	December 14, 2017
Last Verified:	December 2017

Keywords provided by Eastern Cooperative Oncology Group:


neurotoxicity adult diffuse astrocytoma adult oligodendroglioma recurrent adult brain tumor adult mixed glioma

Additional relevant MeSH terms:


Glioma Nervous System Neoplasms Central Nervous System Neoplasms Neurotoxicity Syndromes Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue	Neoplasms by Site Nervous System Diseases Poisoning Chemically-Induced Disorders Temozolomide Dacarbazine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents

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