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