Observation or Radiation Therapy With or Without Combination Chemotherapy in Treating Patients With Low-Grade Glioma

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known whether radiation therapy combined with chemotherapy is more effective than radiation therapy alone in treating patients with low-grade glioma. PURPOSE: Phase II/III trial to evaluate observation and to compare the effectiveness of radiation therapy with or without combination chemotherapy in treating patients with low-grade glioma.

Detailed Description
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OBJECTIVES: Identify the overall survival of low-risk adult patients with supratentorial low-grade glioma who are observed postoperatively. Compare the overall survival of high-risk adult patients with supratentorial low-grade glioma who receive postoperative external beam radiotherapy with or without procarbazine, lomustine, and vincristine (PCV) chemotherapy. Compare the toxic effects of postoperative radiotherapy with or without PCV chemotherapy in patients with unfavorable low-grade glioma. OUTLINE: This is a randomized study. Patients are stratified according to tumor subtype (astrocytoma [mixed-astro dominant or equal astro/oligo mix] vs oligodendroglioma [mixed-oligo dominant]), age (younger than 40 vs at least 40), Karnofsky performance status (60-80% vs 90-100%), and contrast enhancement on preoperative scan (present vs absent). Patients with low-risk disease (younger than 40 years old whose tumors have been surgically removed) are assigned to arm I. Patients with high-risk disease (at least 40 years old or who have had incomplete tumor removal) are randomized to arm II or III. Arm I (low-risk patients): Patients are observed. Patients may receive treatment if tumor recurs. Arm II (high-risk patients): Patients receive daily external beam radiotherapy 5 days a week for 6 weeks. Arm III (high-risk patients): Patients receive radiotherapy as in arm II followed by chemotherapy 1 month later. Chemotherapy consists of oral lomustine on day 1, vincristine IV on days 8 and 29, and oral procarbazine on days 8-21. Each course of chemotherapy lasts 8 weeks. Patients may receive up to 6 courses of chemotherapy. Patients are followed every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter. PROJECTED ACCRUAL: Approximately 252 patients will be accrued within 5.25 years.

Official Title
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A Phase II Study of Observation in Favorable Low-Grade Glioma and a Phase II Study of Radiation With or Without PCV Chemotherapy in Unfavorable Low-Grade Glioma

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 confirmed unifocal or multifocal supratentorial WHO grade II astrocytoma (diffuse fibrillary, protoplasmic, or gemistocytic), oligodendroglioma, or oligoastrocytoma Patients with neurofibromatosis are eligible No other low-grade histologies, including: Pilocytic astrocytoma Subependymal giant cell astrocytoma of tuberous sclerosis Subependymoma Pleomorphic xanthoastrocytoma Presence of a neuronal element such as ganglioglioma Dysneuroembryoplastic epithelial tumor No presence of any high-grade glioma, including: Anaplastic astrocytoma Glioblastoma multiforme Anaplastic oligodendroglioma Anaplastic oligoastrocytoma No tumors in nonsupratentorial or other locations including optic chiasm, optic nerve(s), pons, medulla, cerebellum, or spinal cord No evidence of spread to spinal meninges or noncontiguous cranial meninges (i.e., leptomeningeal gliomatosis) No gliomatosis cerebri PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Hematopoietic: For high-risk patients: Granulocyte count at least 1,500/mm^3 Platelet count normal Hepatic: Bilirubin no greater than 2 times normal SGOT or SGPT no greater than 4 times normal Alkaline phosphatase no greater than 2 times normal Renal: Creatinine no greater than 2 times normal Pulmonary: No chronic lung disease (unless DLCO at least 60%) Neurological: Neurologic function score no greater than 3 Other: Not pregnant or nursing Fertile patients must use effective contraception No other malignancy within the past 5 years except carcinoma in situ of the cervix or nonmelanoma skin cancer No active infection PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: No prior radiotherapy to the head or neck (unless brain is clearly excluded, such as radiotherapy for localized vocal cord cancer) Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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 |
| --- | --- |
| No Intervention: Observation<br>Observation only. | |
| Experimental: Radiation therapy<br>Radiation therapy only. | Radiation: radiation therapy<br> <br> |
| Experimental: Radiation plus PCV chemotherapy<br>Radiation and Procarbazine/CCNU/Vincristine (PCV) chemotherapy | 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 5 years or 80 deaths have been reported. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival |  | From randomization to the date of progression, death or last follow-up. Analysis ours at the same time as the primary outcome analysis. | 
| The severe or worse toxicities (>= grade 3) of unfavorable patients |  | From start of treatment to end of follow-up | 

 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 pilocytic astrocytoma