Celecoxib in Patients With Newly Diagnosed GBM Who Are Receiving Anticonvulsant Drugs and Undergoing RT

Brain and Central Nervous System Tumors Clinical Trial

Official title:

A Pharmacokinetic Study of the Interaction Between Celecoxib and Anticonvulsant Drugs in Patients With Newly Diagnosed Glioblastoma Multiforme Undergoing Radiation Therapy

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00068770
• Other study ID #: NABTT-2100 CDR0000328117
• Secondary ID: U01CA062475NABTT
• Status: Terminated
• Phase: Phase 2
• First received: September 10, 2003
• Last updated: March 17, 2015
• Start date: October 2003
• Est. completion date: May 2006

Study information

• Verified date: March 2015
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: May 2006
• Est. primary completion date: May 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

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.

Locations

Country	Name	City	State
United States	Winship Cancer Institute of Emory University	Atlanta	Georgia
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Abramson Cancer Center of the University of Pennsylvania	Philadelphia	Pennsylvania
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effects of Hepatic Enzyme Inducing Drugs Such as Anticonvulsants, on the PK of Celecoxib	subjects will take one dose of celecoxib and will then have 6 hours of blood draws, day 2 subject will take 2 doses of celecoxib 8 hours apart with 2 additional blood samples, one hour apart. Subject, will continue to take 2 doses of celecoxib for 6 weeks, with a sample (PK) drawn every week prior to the first dose of the week. Comparison of Cmax of Celecoxib is reported	First dose of celecoxib through completion of radiation, 6 weeks.	No
Secondary	Overall Survival	duration of survival when celecoxib is administered concurrently with radiation in pts with newly diagnosed glioblastoma multiforme	date pt started treatment to date pt last known alive	No