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.

Condition	Treatment or Intervention	Phase
adult anaplastic astrocytoma adult anaplastic oligodendroglioma adult brain tumor adult glioblastoma Mixed Gliomas	Drug: celecoxib  Drug: cyclophosphamide  Drug: etoposide  Drug: thalidomide  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: chemosensitization/potentiation  Procedure: chemotherapy  Procedure: enzyme inhibitor therapy  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

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

Massachusetts
      Brigham and Women's Hospital, Boston,  Massachusetts,  02115,  United States
      Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston,  Massachusetts,  02115,  United States
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114,  United States

Study chairs or principal investigators

Patrick Y. Wen, MD,  Study Chair,  Dana-Farber/Harvard Cancer Center   

Study ID Numbers:  CDR0000257584; DFCI-01278; NCI-G02-2117; CELGENE-2001-P-001757/3; NCT00047281
Record last reviewed:  January 2005
Last Updated:  January 6, 2005
Record first received:  October 3, 2002
ClinicalTrials.gov Identifier:  NCT00047281
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08