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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Radiation: radiation therapy
* Drug: Celecoxib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: p450 ( +EIASD)<br>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: radiation therapy<br>* Radiation is standard treatment 6000cGy in 30 fractions. Patients will receive celecoxib 400 mg bid during RT treatment<br>* Other names: RT;Drug: Celecoxib<br>* 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.<br>* Other names: Cox2;|
| Active Comparator: nonp450 (-EIASD)<br>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: radiation therapy<br>* Radiation is standard treatment 6000cGy in 30 fractions. Patients will receive celecoxib 400 mg bid during RT treatment<br>* Other names: RT;Drug: Celecoxib<br>* 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.<br>* Other names: Cox2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, adult giant cell glioblastoma, adult gliosarcoma