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

Dana-Farber Cancer Institute

Status and phase

Completed

Phase 2

Conditions

Brain and Central Nervous System Tumors

Treatments

Drug: celecoxib

Drug: cyclophosphamide

Drug: thalidomide

Drug: etoposide

Study type

Interventional

Funder types

Other

Industry

NIH

Identifiers

NCT00047281

CDR0000257584

P30CA006516 (U.S. NIH Grant/Contract)

CELGENE-2001-P-001757/3

01-278

NCI-G02-2117

Details and patient eligibility

About

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.

Full description

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.

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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