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

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.

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