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

NCT ID: NCT00068770

Last Updated: 2015-03-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-10-31
• Study Completion Date: 2006-05-31

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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

radiation therapy

Intervention Type: RADIATION

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

Celecoxib

Intervention Type: DRUG

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.

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

Group Type: ACTIVE_COMPARATOR

radiation therapy

Intervention Type: RADIATION

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

Celecoxib

Intervention Type: DRUG

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.

Interventions

radiation therapy

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

Intervention Type: RADIATION

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.

Intervention Type: DRUG

Other Intervention Names

RT; Cox2

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stuart A. Grossman, MD

Role: STUDY_CHAIR

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 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

Comprehensive Cancer Center at Wake Forest University

Winston-Salem, North Carolina, United States

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, United States

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 18287342 (View on PubMed)

Other Identifiers

U01CA062475

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NABTT-2100

Identifier Type: -

Identifier Source: secondary_id

JHOC-NABTT-2100

Identifier Type: -

Identifier Source: secondary_id

NABTT-2100 CDR0000328117

Identifier Type: -

Identifier Source: org_study_id