Clinical Trial Finder

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

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.

• - Group A: Patients treated with any of the following anticonvulsant drugs that induce hepatic metabolic enzymes: - Phenytoin.

• - Carbamazepine.

• - Phenobarbital.

• - Primidone.

• - Oxcarbazepine.

• - Group B: 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.

Arms

Active Comparator: p450 ( +EIASD)

on p450 inhibitor (Patients taking anttiseizure drugs that are known to induce the hepatic drug-metabolizing enzymes - including phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine) celecoxib and radiation therapy will be adminstered with this arm

Active Comparator: nonp450 (-EIASD)

not on p450 inhibitor (Patients either NOT taking anti-seizure drugs or ones that are known to not significantly influence the hepatic drug-metabolizing enzymes - including gabapentin, lamotrigine, valproic acid, levetiracetam, tiagabine,topiramate, zonisamide and filbamate. celecoxib and radiation therapy will be adminstered with this arm

Interventions

Radiation: - radiation therapy

Radiation is standard treatment 6000cGy in 30 fractions. Patients will receive celecoxib 400 mg bid during RT treatment

Drug: - Celecoxib

Celecoxib will begin 1 week prior to RT at 400mg bid orally. One day 1 only 1 dose will be administered. Starting on day 2 and throughout treatment until progression, 2 doses will be administered at least 12 hours apart. Celecoxib will continue throughout the 6 week course of RT.