Clinical trial NCT00068770: Celecoxib in Patients With Newly Diagnosed GBM Who Are Receiving Anticonvulsant Drugs and Undergoing RT
Official title: A Pharmacokinetic Study of the Interaction Between Celecoxib and Anticonvulsant Drugs in Patients With Newly Diagnosed Glioblastoma Multiforme Undergoing Radiation Therapy
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Keywords: adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-09-11
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Effects of Hepatic Enzyme Inducing Drugs Such as Anticonvulsants, on the PK of Celecoxib
timeFrame: First dose of celecoxib through completion of radiation, 6 weeks.
Secondary outcomes:
measure: Overall Survival
timeFrame: date pt started treatment to date pt last known alive
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Abramson Cancer Center of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Stuart A. Grossman, MD
role: STUDY_CHAIR
References:
citation: Grossman SA, Olson J, Batchelor T, Peereboom D, Lesser G, Desideri S, Ye X, Hammour T, Supko JG; New Approaches to Brain Tumor Therapy CNS Consortium. Effect of phenytoin on celecoxib pharmacokinetics in patients with glioblastoma. Neuro Oncol. 2008 Apr;10(2):190-8. doi: 10.1215/15228517-2007-055. Epub 2008 Feb 20.