Celecoxib in Patients With Newly Diagnosed GBM Who Are Receiving Anticonvulsant Drugs and Undergoing RT
A Pharmacokinetic Study of the Interaction Between Celecoxib and Anticonvulsant Drugs in Patients With Newly Diagnosed Glioblastoma Multiforme Undergoing Radiation Therapy
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.
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612-9497
- H. Lee Moffitt Cancer Center and Research Institute
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Winship Cancer Institute of Emory University
-
-
Maryland
-
Baltimore, Maryland, United States, 21231-2410
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
-
-
Massachusetts
-
Boston, Massachusetts, United States, 02114-2617
- Massachusetts General Hospital Cancer Center
-
-
North Carolina
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Winston-Salem, North Carolina, United States, 27157-1030
- Comprehensive Cancer Center at Wake Forest University
-
-
Ohio
-
Cleveland, Ohio, United States, 44195
- Cleveland Clinic Taussig Cancer Center
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104-4283
- Abramson Cancer Center of the University of Pennsylvania
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
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 |
Radiation is standard treatment 6000cGy in 30 fractions.
Patients will receive celecoxib 400 mg bid during RT treatment
Other Names:
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.
Other Names:
|
|
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 |
Radiation is standard treatment 6000cGy in 30 fractions.
Patients will receive celecoxib 400 mg bid during RT treatment
Other Names:
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Effects of Hepatic Enzyme Inducing Drugs Such as Anticonvulsants, on the PK of Celecoxib
Time Frame: First dose of celecoxib through completion of radiation, 6 weeks.
|
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.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall Survival
Time Frame: date pt started treatment to date pt last known alive
|
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
|
Collaborators and Investigators
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Neoplasms
- Neoplasms by Site
- Nervous System Neoplasms
- Central Nervous System Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anti-Inflammatory Agents, Non-Steroidal
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Cyclooxygenase Inhibitors
- Cyclooxygenase 2 Inhibitors
- Celecoxib
Other Study ID Numbers
- NABTT-2100 CDR0000328117
- U01CA062475 (U.S. NIH Grant/Contract)
- NABTT-2100
- JHOC-NABTT-2100
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