Combination Chemotherapy Following Radiation Therapy in Treating Patients With Malignant Glioma

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug may kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of combination chemotherapy following radiation therapy in treating patients who have malignant glioma.

Detailed Description
-----------------
OBJECTIVES: Determine the safety and efficacy of extended low-dose temozolomide when combined with carmustine after radiotherapy in patients with malignant glioma. Determine the maximum tolerated dose of this combination in this patient population. Determine time to progression as measured from baseline gadolinium-enhanced magnetic resonance imaging in patients treated with this regimen. OUTLINE: This is a dose-escalation study of temozolomide. Patients receive oral temozolomide once daily on days 1-28 and carmustine IV over 1-3 hours beginning within 72 hours after starting temozolomide. Courses repeat every 8 weeks for up to 1 year in the absence of unacceptable toxicity or disease progression. 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 6 patients experience dose-limiting toxicity. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 3-24 patients will be accrued for this study within 1-2 years.

Official Title
-----------------
A Phase I Study of Extended Low Dose Temozolomide (SCH 52365, Temodar (R)) and Carmustine (BCNU) in the Treatment of Malignant Gliomas After Radiation Therapy

Conditions
-----------------
Brain and Central Nervous System Tumors

Intervention / Treatment
-----------------
* Drug: carmustine
* Drug: temozolomide


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed malignant glioma Glioblastoma Gliosarcoma High-grade glioma Anaplastic astrocytoma Anaplastic mixed oligoastrocytoma Anaplastic oligodendroglioma Anaplastic ependymoma Must have completed radiotherapy PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life expectancy: More than 3 months Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 10 g/dL Hepatic: Bilirubin less than 1.5 times upper limit of normal (ULN) SGOT/SGPT less than 3 times ULN Alkaline phosphatase less than 2 times ULN Renal: BUN less than 1.5 times ULN Creatinine less than 1.5 times ULN Pulmonary: Pulmonary function test with diffusion greater than 50 OR Clearance by the pulmonary service Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception HIV negative No AIDS-related illness No nonmalignant systemic disease that would preclude study No acute infection requiring IV antibiotics No psychiatric condition that would preclude study compliance No frequent vomiting or medical condition that would interfere with oral medication intake (e.g., partial bowel obstruction) No other prior or concurrent malignancy except surgically cured carcinoma in situ of the cervix or basal cell or squamous cell skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy No prior biologic therapy Chemotherapy: No prior chemotherapy Endocrine therapy: Not specified Radiotherapy: See Disease Characteristics At least 2 weeks since prior radiotherapy Surgery: Not specified

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carmustine|nan|
|Drug: temozolomide|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adult glioblastoma, adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult mixed glioma, adult giant cell glioblastoma, adult gliosarcoma, adult anaplastic ependymoma