Radiation Therapy With or Without Chemotherapy in Treating Patients With Anaplastic Oligodendroglioma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining chemotherapy with radiation therapy may kill more tumor cells. PURPOSE: Randomized phase III trial to compare the effectiveness of radiation therapy with or without chemotherapy in treating patients who have anaplastic oligodendroglioma.

Detailed Description
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OBJECTIVES: Compare the overall survival and time to tumor progression in patients with unifocal or multifocal, supratentorial, pure or mixed anaplastic oligodendroglioma treated with radiotherapy with or without procarbazine, lomustine, and vincristine (PCV). Compare the toxic effects of these 2 regimens in these patients. Compare the quality of life and neurologic function of patients treated with these 2 regimens. OUTLINE: This is a randomized study. Patients are stratified by age (under 50 vs 50 and over), Karnofsky performance status (60-70% vs 80-100%), and tumor grade (moderately vs highly anaplastic). Within 8 weeks after diagnostic surgery, patients are randomized to 1 of 2 treatment arms. Arm I: Within 2 weeks after randomization, patients receive oral lomustine on day 1, oral procarbazine on days 8-21, and vincristine IV on days 8 and 29 (PCV). Treatment continues every 6 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Beginning within 6 weeks after day 29 of course 4, patients undergo radiotherapy 5 days a week for 5.6 weeks followed by boost radiotherapy 5 days a week for 1 week. Arm II: Within 2 weeks after randomization, patients undergo radiotherapy as in arm I. Quality of life is assessed at baseline; at time of CT or MRI scans during study; and every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter after completion of study therapy. Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 292 patients (146 per arm) will be accrued for this study within 5.4 years.

Official Title
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Phase III Intergroup Randomized Comparison of Radiation Alone vs. Pre-Radiation Chemotherapy for Pure and Mixed Anaplastic Oligodendrogliomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: lomustine
* Drug: procarbazine hydrochloride
* Drug: vincristine sulfate
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven unifocal or multifocal, supratentorial, pure or mixed anaplastic oligodendroglioma Prior suspected or proven low-grade glioma allowed if current histologic proof of pure or mixed anaplastic oligodendroglioma Tumor must contain an unequivocal (at least 25%) oligodendroglial element and have 2 or more anaplastic features, 1 of which must be frequent mitoses or endothelial proliferation For mixed tumors, the non-oligodendroglial element must be astrocytic and the oligodendroglial or astroglial component may be anaplastic No evidence of spinal drop metastasis or spread to noncontiguous meninges MRI of spine not required for asymptomatic patients and patients not excluded based on pathologic evidence of local meningeal infiltration by underlying tumor No tumor that is predominantly located in the posterior fossa (i.e., brainstem or cerebellum) No spinal cord tumors PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 150,000/mm^3 Hepatic: Bilirubin no greater than 2 times normal Serum glutamate oxaloacetate transaminase (SGOT) no greater than 2 times normal Alkaline phosphatase no greater than 2 times normal Renal: Creatinine no greater than 1.5 times normal Pulmonary: No chronic lung disease unless diffusion capacity of lung for carbon monoxide (DLCO) is at least 60% predicted Other: No active infection No other malignancy within the past 5 years except nonmelanomatous skin cancer or carcinoma in situ of the cervix Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: No concurrent steroids as antiemetics Concurrent steroids allowed to control central nervous system (CNS) symptoms due to tumor-associated or radiotherapy-associated cerebral edema Radiotherapy: No prior radiotherapy to brain or head/neck Surgery: Prior surgery 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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Radiation therapy (RT) alone<br>Radiation therapy (RT) alone - External Beam RT 59.4 Gy (1.8 Gy x 33 fractions, 5 days a week) to MR defined tumor volume. | Radiation: radiation therapy<br> <br> |
| Experimental: Intensive pre-treatment chemotherapy and radiation therapy<br>Intensive pre-treatment chemotherapy (Day 1 CCNU 130 mg/m2 p.o., Day 8 - Vincristine 1.4 mg/m2 i.v., Days 8-21 - Procarbazine 75 mg/m2 p.o., Day 29 - Vincristine 1.4 mg/m2 i.v.) followed by radiation therapy (External Beam RT 59.4 Gy (1.8 Gy x 33 fractions, 5 days a week) to MR defined tumor volume). | Drug: lomustine<br> <br> Drug: procarbazine hydrochloride<br> <br> Drug: vincristine sulfate<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to tumor progression |  | From randomization to date of progression or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. | 
| Frequency of severe (>= Grade 3) toxicities |  | From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 3 years. | 

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