Thalidomide, Celecoxib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Malignant Glioma

Study Overview
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Brief Summary
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RATIONALE: Thalidomide and celecoxib may stop the growth of tumor cells by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining thalidomide and celecoxib with etoposide and cyclophosphamide may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining thalidomide and celecoxib with etoposide and cyclophosphamide in treating patients who have relapsed or refractory malignant glioma.

Detailed Description
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OBJECTIVES: Determine the efficacy of thalidomide, celecoxib, etoposide, and cyclophosphamide, in terms of 6-month progression-free survival, in patients with relapsed or refractory malignant glioma. Determine the overall survival of patients treated with this regimen. Determine the toxic effects of this regimen in these patients. Determine the radiographic response in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive oral thalidomide once daily and oral celecoxib twice daily on days 1-42, oral etoposide once daily on days 1-21, and oral cyclophosphamide once daily on days 22-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months. PROJECTED ACCRUAL: A total of 48 patients (32 with glioblastoma multiforme and 16 with anaplastic glioma) will be accrued for this study within 2 years.

Official Title
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Trial Of Oral Thalidomide, Celecoxib, Etoposide And Cyclophosphamide In Adult Patients With Relapsed Or Progressive Malignant Gliomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: celecoxib
* Drug: cyclophosphamide
* Drug: etoposide
* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed intracranial malignant glioma, including glioblastoma multiforme, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed oligoastrocytoma, or malignant astrocytoma not otherwise specified Unequivocal evidence of relapsed or refractory disease by MRI or CT scan and/or tumor resection Steroid therapy prior to MRI or CT scan must have been at a stable dose for at least 5 days Failed prior radiotherapy Must have confirmation of true progression rather than radiation necrosis if previously treated with interstitial brachytherapy or stereotactic radiosurgery PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 60-100% Life expectancy More than 2 months Hematopoietic Absolute neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hemoglobin greater than 9 g/dL No history of bleeding disorder Hepatic Bilirubin less than 1.5 mg/dL SGPT less than 2.5 times normal Alkaline phosphatase less than 2.5 times normal Renal Creatinine less than 1.5 times upper limit of normal (ULN) OR BUN less than 1.5 times ULN Cardiovascular No deep vein thrombosis within the past 3 weeks (must be clinically stable) Pulmonary No pulmonary embolism within the past 3 weeks (must be clinically stable) Other No peripheral neuropathy grade 2 or greater No active infection No other serious concurrent medical illness No concurrent illness that may obscure toxicity or dangerously alter drug metabolism No other malignancy within the past 3 years except nonmelanoma skin cancer or carcinoma in situ of the cervix Must participate in the System for Thalidomide Education and Prescribing Safety program Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 forms of effective contraception for 1 month before, during, and for 1 month after study PRIOR CONCURRENT THERAPY: Biologic therapy No prior oral thalidomide or celecoxib for more than 2 months duration Chemotherapy No prior oral etoposide or cyclophosphamide for more than 2 months duration Prior standard-dose IV etoposide and cyclophosphamide allowed Endocrine therapy See Disease Characteristics Concurrent steroids allowed Radiotherapy See Disease Characteristics At least 4 weeks since prior radiotherapy Surgery See Disease Characteristics Prior surgery for relapsed or refractory disease allowed Recovered from prior surgery No concurrent surgery Other No other concurrent investigational agents or treatment No other concurrent anticancer therapy Concurrent antiseizure medications allowed

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: celecoxib|nan|
|Drug: cyclophosphamide|nan|
|Drug: etoposide|nan|
|Drug: thalidomide|nan|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult anaplastic astrocytoma, adult anaplastic oligodendroglioma, adult glioblastoma, adult mixed glioma, recurrent adult brain tumor, adult giant cell glioblastoma, adult gliosarcoma