Radiation Therapy or Temozolomide in Treating Patients With Gliomas

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. 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 than temozolomide in treating gliomas. PURPOSE: This randomized phase III trial is studying radiation therapy to see how well it works compared to temozolomide in treating patients with gliomas.

Detailed Description
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OBJECTIVES: Primary Compare the progression-free survival of patients with low-grade gliomas treated with radiotherapy vs temozolomide. Secondary Compare the overall survival of patients treated with these regimens. Determine whether the incidence of late toxicity can be decreased in patients who are randomized to receive temozolomide. Compare the toxic effects of these regimens in these patients. Compare the quality of life of patients treated with these regimens. OUTLINE: This is a randomized, controlled, multicenter study. Patients are stratified according to participating center, chromosome 1p status (deleted vs normal vs undeterminable), contrast enhancement on MRI (yes vs no), age (< 40 years vs ≥ 40 years), and WHO performance status (0 or 1 vs 2). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo radiotherapy once daily, 5 days a week, for a total of 28 fractions (i.e., 5½ weeks). Arm II: Patients receive oral temozolomide once daily on days 1-21. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and then every 3 months until disease progression. After completion of study treatment, patients are followed every 6 months for survival. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A minimum of 699 patients (a total of 466 randomized [233 per treatment arm]) will be accrued for this study within 5 years.

Official Title
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Primary Chemotherapy With Temozolomide Versus Radiotherapy in Patients With Low Grade Gliomas After Stratification for Genetic 1p Loss: A Phase III Study

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: temozolomide
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed low-grade glioma, including any of the following types: Astrocytoma (gemistocytic, fibrillary, or protoplasmatic) Oligoastrocytoma Oligodendroglioma WHO grade II disease Supratentorial tumor location only RTOG neurological function 0-3 Not a candidate for surgical treatment alone Requires treatment, as determined by ≥ 1 of the following criteria: Age ≥ 40 years Radiologically-proven progressive lesion New or worsening neurological symptoms other than seizures only (e.g., focal deficits, signs of increased intracranial pressure, or mental deficits) Intractable seizures, defined by both of the following criteria: Experiences persistent seizures that interfere with everyday life activities except driving a car Failed 3 anti-epileptic drug regimens, including ≥ 1 combination regimen Tumor material (paraffin-embedded) or histopathologic slides available PATIENT CHARACTERISTICS: Age 18 and over Performance status WHO 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic No chronic hepatitis B or C infection Bilirubin ≤ 1.5 times upper limit of normal (ULN) AST or ALT ≤ 2.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Renal Creatinine ≤ 1.5 times ULN Other Not pregnant or nursing Fertile patients must use effective contraception during and for 6 months after completion of study treatment No known HIV positivity No other serious medical condition No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or nonmelanoma skin cancer No psychological, familial, sociological, or geographical condition that would preclude study participation No medical condition that would preclude receiving oral medication (e.g., frequent vomiting or partial bowel obstruction) PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent growth factors for elevating absolute neutrophil counts for the purpose of temozolomide administration No concurrent epoetin alfa No concurrent immunotherapy or biologic therapy Chemotherapy No prior chemotherapy No other concurrent chemotherapy, including adjuvant chemotherapy for patients randomized to undergo radiotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy to the brain No concurrent integrated boost with intensity-modulated radiotherapy Surgery Recovered from prior surgery No concurrent surgical tumor debulking Other No prior randomization to this study No other concurrent investigational drugs No concurrent regular use of agents known to be radiosensitizers or radioprotectors (e.g., cyclooxygenase-2 inhibitors, thalidomide, or amifostine) during study radiotherapy Occasional use of nonsteroidal anti-inflammatory drugs for pain allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: radiotherapy<br>Radiotherapy (control arm), 50.4 Gy, standard fractionation (28 x 1.8 Gy), conformal techniques | Radiation: radiation therapy<br>* 50.4 Gy, standard fractionation (28 x 1.8 Gy), conformal techniques<br>|
| Experimental: Temozolomide<br>Temozolomide 75 mg/m2 daily x 21 days, q 28 days until progression or for max. 12 cycles (experimental arm) | Drug: temozolomide<br>* Temozolomide 75 mg/m2 daily x 21 days, q 28 days until progression or for max. 12 cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 years | 
| Quality of life as measured by QLQ-C30 v3.0 and EORTC BN-20 |  | every 3 months until progression, and then every 6 months until death | 
| Mini-Mental State Examination |  | every 3 months until progression, and then every 6 months until death | 
| Adverse events as measured by CTCAE v3.0 |  | As indicated in the protocol | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult oligodendroglioma, adult diffuse astrocytoma, adult mixed glioma