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

Phase 2TerminatedNCT00068770

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins35 enrolled

Overview

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.

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

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Interventions

radiation therapyRADIATION

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

CelecoxibDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (7)

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

Outcomes

Primary Outcomes

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

Time frame: First dose of celecoxib through completion of radiation, 6 weeks.

Secondary Outcomes

Overall Survival

duration of survival when celecoxib is administered concurrently with radiation in pts with newly diagnosed glioblastoma multiforme

Time frame: date pt started treatment to date pt last known alive