Clinical trial NCT00068770
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma adult giant cell glioblastoma adult gliosarcoma
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Start date: 2003-10-01; Completion date: 2006-05-01
Enrollment: 35 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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: arm 1: 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 arm 2: 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: intervention 1: radiation therapy intervention 2: Celecoxib
Intervention descriptions: intervention 1: Radiation is standard treatment 6000cGy in 30 fractions. Patients will receive celecoxib 400 mg bid during RT treatment intervention 2: 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.

Protocol documents: