Radiation Therapy with or without Temozolomide in Treating Patients with Low-Grade Glioma
Basic Trial Information
|Phase III||Biomarker/Laboratory analysis, Supportive care, Treatment||18 and over||E3F05|
NCI-2011-01971, CDR0000654697, ECOG-E3F05, NCT00978458
This randomized phase III trial studies radiation therapy to see how well it works with or without temozolomide in treating patients with low-grade glioma. 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. Temozolomide is a drug used in chemotherapy that may work to stop the growth of tumor cells by killing the cells. It is not yet known whether radiation therapy is more effective with or without temozolomide in treating patients with low-grade glioma.
Further Study Information
I. To determine whether the addition of temozolomide to fractionated radiotherapy improves the progression-free survival (PFS) of patients requiring treatment for low-grade gliomas.
II. To determine whether the addition of temozolomide to fractionated radiotherapy improves the median overall survival (OS) of patients with low-grade gliomas requiring treatment.
I. To determine whether combination therapy with temozolomide and radiotherapy improves or maintains cognition and quality of life (QOL) compared to radiotherapy alone.
II. To compare the severe or worse toxicities (>= grade 3) of patients receiving radiation therapy alone or radiation therapy plus temozolomide chemotherapy.
III. To assess the impact of the presence or absence of 1p and 19q deletion on PFS and OS, and to determine the impact of 1p and 19q status on PFS and OS in patients receiving chemotherapy.
V. To create a tumor and tissue bank, including plasma and germ line deoxyribonucleic acid (DNA), within the Eastern Cooperative Oncology Group (ECOG)-American College of Radiology Imaging Network (ACRIN) Central Biorepository and Pathology Facility (CBPF).
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients undergo 3-dimensional conformal or intensity-modulated radiotherapy once daily (QD) 5 days a week for 5½ weeks (28 fractions).
ARM II: Patients undergo radiotherapy as in Arm I and receive concurrent temozolomide orally (PO) QD for 5½ weeks. Beginning 28 days after completion of chemoradiotherapy, patients receive temozolomide alone PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up periodically for up to 15 years.
The patient must currently have at least one of the following:
Uncontrolled symptoms, defined as any of the following:
- Headaches associated with mass effect
- Uncontrolled seizures despite 2 different antiepileptic drug regimens (i.e., 2 antiepileptic drugs tested either sequentially or in combination)
- Focal neurological symptoms
- Cognitive symptoms or deficits OR
Tumor progression by serial magnetic resonance imaging (MRIs), defined as any of the following:
- New or progressive enhancement
- New or progressive T2 or fluid attenuated inversion recovery (FLAIR) signal abnormality OR
Age >= 40 years
- NOTE: Patients aged less than 40 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 ineligible
Patient must be able to undergo MRI with and without contrast; patients who are unable to undergo MRI are ineligible
MRI and chest x-ray within 6 weeks prior to pre-registration; a postoperative MRI is required for all patients who underwent open biopsy, or resection, but is not mandatory following stereotactic biopsy
Karnofsky performance status >= 60%
Bilirubin =< 2 x upper limit of normal (ULN)
Patient must be at least two weeks post any brain surgery (whether stereotactic biopsy, open biopsy or resection) at the time of randomization
No previous radiation, cytotoxic chemotherapy, radio surgery, or investigational treatment directed at the brain tumor at any time; no limit on number of previous surgical procedures of this tumor
Aspartate aminotransferase (AST) =< 3 x ULN (serum glutamic oxaloacetic transaminase [SGOT])
Women must not be pregnant or breast-feeding
All females of childbearing potential must have a blood test or urine study within 2 weeks prior to randomization to rule out pregnancy
No medical disorder that increases risks of radiation or temozolomide (TMZ) chemotherapy; no uncontrolled infection; no known positivity for human immunodeficiency virus (HIV); no other disorder limiting expected survival to < 5 years
Hematocrit >= 30%
1p/19q deletion status assessment as determined by the Mayo Cytogenetics Laboratory has been received
No other diagnosed malignancy (except non-melanoma skin cancer or cervical carcinoma in situ, which are allowable), unless the patient has been disease-free for at least 5 years
Tumors must be supratentorially located
Pathological diagnosis of astrocytoma grade 2, oligodendroglioma grade 2, or oligoastrocytoma grade 2 (mixed glioma containing astrocytoma and oligodendroglioma); pilocytic astrocytoma, ganglioglioma, pleomorphic xanthoastrocytoma, or dysembryoplastic neuroepithelial tumors are not eligible
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, and a pathological diagnosis of a grade 3 or grade 4 glioma must not have been made at any time
No previous radiation treatment to the head (unless the ports for that radiation entirely excluded the brain) for any condition
Platelet >= 100,000/mm^3
Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception
White blood count (WBC) >= 3,000/mm^3
Absolute neutrophil count (ANC) >= 1,500/mm^3
Patients must have paraffin-embedded tumor specimen available for submission for pathological review and determination of 1p/19q deletion status
NOTE: it is recommended that patients not be pre-registered until the required tumor specimens are on hand and ready for submission; if submission of tissue will be submitted more than 5 working days after pre-registration, immediately notify the Mayo Clinic Cytogenetics Laboratory via email
Creatinine =< 2.0 x ULN
Patients who have undergone gross total resection and have no detectable residual disease are eligible
Must be able to start treatment with radiation therapy (RT) within 2 weeks or 10 working days at a qualified center (to be defined by the Radiation Oncology chair) and to start TMZ prescribed at a participating center within 2 weeks or 10 working days of randomization
Alanine aminotransferase (ALT) =< 3 x ULN (serum glutamate pyruvate transaminase [SGPT])
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
ECOG-ACRIN Cancer Research Group
- National Cancer Institute
Northern Indiana Cancer Research Consortium CCOP
Tufts Medical Center
John Scott Nystrom
John Scott Nystrom
AnMed Health Hospital
Charles E. Bowers
Charles E. Bowers
Mayo Clinic Health System Eau Claire Hospital - Luther Campus
Daniel P. Burns
Daniel P. Burns
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00978458
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.