RATIONALE: Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. It is not yet known whether the effectiveness of celecoxib in treating glioblastoma multiforme is decreased in patients who are receiving anticonvulsant drugs and undergoing radiation therapy.

PURPOSE: Phase II trial to study the effectiveness of celecoxib in treating patients who are receiving anticonvulsant drugs and undergoing radiation therapy for newly diagnosed glioblastoma multiforme.

Condition	Treatment or Intervention	Phase
adult glioblastoma adult giant cell glioblastoma adult gliosarcoma	Drug: celecoxib  Procedure: enzyme inhibitor therapy  Procedure: radiation therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the effects of hepatic enzyme-inducing drugs, such as anticonvulsants, on the pharmacokinetics of celecoxib in patients with newly diagnosed glioblastoma multiforme undergoing radiotherapy.
• Determine the effects of steroids on the pharmacokinetics of celecoxib in these patients.

Secondary

• Determine the safety of celecoxib in these patients.
• Determine the duration of survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients are assigned to 1 of 2 groups based on anticonvulsant therapy.

• Patients treated with any of the following anticonvulsant drugs that induce hepatic metabolic enzymes:
• Phenytoin
• Carbamazepine
• Phenobarbital
• Primidone
• Oxcarbazepine
• Patients treated with any of the following anticonvulsant drugs that cause modest or no induction of hepatic metabolic enzymes OR no anticonvulsant drug:
• Gabapentin
• Lamotrigine
• Valproic acid
• Levetiracetam
• Tiagabine
• Topiramate
• Zonisamide
• Felbamate
• Induction therapy: Patients in both groups receive oral celecoxib twice* daily on weeks 1-11 and undergo radiotherapy 5 days a week on weeks 2-7.
• Maintenance therapy: Patients receive oral celecoxib twice daily. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. NOTE: *Patients receive only 1 dose on the first day of celecoxib administration.

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 44 patients (22 per group) will be accrued for this study within approximately 8 months.

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

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed glioblastoma multiforme
• Supratentorial
• Grade IV astrocytoma

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• Karnofsky 60-100%

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 9.0 g/dL

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• Transaminases no greater than 4 times upper limit of normal

Renal

• Creatinine no greater than 1.7 mg/dL
• Creatinine clearance at least 60 mL/min
• No prior renal toxicity with nonsteroidal anti-inflammatory drugs

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Mini mental score at least 15
• No history of peptic disease
• No serious concurrent infection
• No other medical illness that would preclude study participation
• No other malignancy within the past 5 years except curatively treated carcinoma in situ or basal cell skin cancer
• No allergy to sulfonamides
• Able to tolerate cyclo-oxygenase-2 (COX-2) inhibitors

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy or biologic agents for the malignancy, including any of the following:
• Immunotoxins
• Immunoconjugates
• Antisense agents
• Peptide receptor antagonists
• Interferons
• Interleukins
• Tumor-infiltrating lymphocytes
• Lymphokine-activated killer cells
• Gene therapy
• No concurrent prophylactic growth factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])

Chemotherapy

• No prior chemotherapy for the malignancy

Endocrine therapy

• No prior hormonal therapy for the malignancy
• Prior glucocorticoid therapy allowed
• Concurrent corticosteroids allowed provided there has been no dose increase within the past 5 days

Radiotherapy

• No prior radiotherapy for the malignancy

Surgery

• Recovered from prior surgery

Other

• At least 1 week since prior fluconazole
• More than 10 days since prior anticonvulsant drugs that induce hepatic metabolic enzymes (Group A)
• No other prior therapy for the malignancy
• No concurrent enrollment in another therapeutic clinical trial
• No concurrent fluconazole

Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States
Georgia
      Winship Cancer Institute of Emory University, Atlanta,  Georgia,  30322,  United States
Maryland
      Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore,  Maryland,  21231-2410,  United States
Massachusetts
      Massachusetts General Hospital Cancer Center, Boston,  Massachusetts,  02114-2617,  United States
North Carolina
      Comprehensive Cancer Center at Wake Forest University, Winston Salem,  North Carolina,  27157-1030,  United States
Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States
Pennsylvania
      Abramson Cancer Center of the University of Pennsylvania, Philadelphia,  Pennsylvania,  19104-4283,  United States

Study chairs or principal investigators

Stuart A. Grossman, MD,  Study Chair,  Sidney Kimmel Cancer Center   

Study ID Numbers:  CDR0000328117; NABTT-2100; JHOC-NABTT-2100; NCT00068770
Record last reviewed:  January 2005
Last Updated:  January 7, 2005
Record first received:  September 10, 2003
ClinicalTrials.gov Identifier:  NCT00068770
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08