Temozolomide Plus Lomustine Followed by Radiation Therapy in Treating Patients With High-Grade Malignant Glioma

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 more than one chemotherapy drug with radiation therapy may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of temozolomide plus lomustine followed by radiation therapy in treating patients who have high-grade malignant glioma.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of temozolomide when administered with lomustine in patients with high-grade malignant gliomas. Determine the dose-limiting toxic effects of this regimen in these patients. Evaluate the feasibility of radiotherapy after this treatment regimen in this patient population. Evaluate the radiographic responses in patients treated with this regimen. OUTLINE: This is a multicenter, dose-escalation study of temozolomide. Patients receive oral temozolomide on days 1-5 and oral lomustine on day 1. Treatment continues every 28 days, if blood counts have recovered, for 2 courses in the absence of disease progression or unacceptable toxicity. Patients then undergo radiotherapy on days 1-5 weekly for 6 weeks. Patients continue the same chemotherapy regimen for up to 6 more courses beginning 4 weeks after completion of radiotherapy. Cohorts of 3-6 patients receive escalating doses of temozolomide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients are followed for survival. PROJECTED ACCRUAL: A total of 3-30 patients will be accrued for this study.

Official Title
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A Phase I Study of Temozolomide and CCNU in Pediatric Patients With Newly Diagnosed Incompletely Resected Non-Brainstem High-Grade Gliomas

Conditions
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Brain Tumor, Central Nervous System Tumor

Intervention / Treatment
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* Drug: lomustine
* Drug: temozolomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed high-grade malignant glioma of one of the following subtypes: Glioblastoma Anaplastic astrocytoma Anaplastic oligoastrocytoma Gliomatosis cerebri No disseminated disease or primary spinal cord malignancies Measurable intracranial residual disease by MRI PATIENT CHARACTERISTICS: Age: 3 and over Under 22 at time of diagnosis Performance status: Karnofsky 50-100% if over 10 years of age Lansky 50-100% if 10 years of age or under Life expectancy: At least 8 weeks Hematopoietic: Absolute neutrophil count at least 1,000/mm^3 Platelet count at least 100,000/mm^3 (transfusion independent) Hemoglobin at least 8.0 g/dL (RBC transfusions allowed) Hepatic: Bilirubin no greater than 1.5 times normal for age SGPT no greater than 2.5 times normal for age Albumin at least 2 g/dL Renal: Creatinine no greater than 1.5 times normal for age OR Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal for age Pulmonary: No dyspnea at rest No exercise intolerance Pulse oximetry at least 94% Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No uncontrolled infection PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy No concurrent prophylactic hematopoietic growth factors Chemotherapy: No prior chemotherapy Endocrine therapy: Prior corticosteroid therapy allowed No concurrent corticosteroids as antiemetic Radiotherapy: No prior radiotherapy Surgery: No more than 31 days since prior maximal neurosurgical procedure Other: No concurrent phenobarbital or cimetidine

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 21 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pre and Post radiation Chemotherapy<br> | Drug: lomustine<br> <br> Drug: temozolomide<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | This trial is a phase I evaluation of temozolomide in combination with a fixed dose of CCNU with the starting dose for temozolomide | Length of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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childhood high-grade cerebral astrocytoma