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

This study has been terminated.
(EORTC trail showed TMZ & RT conferred significant survivial in this population)
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00068770
First received: September 10, 2003
Last updated: March 17, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Radiation: radiation therapy
Drug: Celecoxib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pharmacokinetic Study of the Interaction Between Celecoxib and Anticonvulsant Drugs in Patients With Newly Diagnosed Glioblastoma Multiforme Undergoing Radiation Therapy

Resource links provided by NLM:


Further study details as provided by Sidney Kimmel Comprehensive Cancer Center:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Overall Survival [ Time Frame: date pt started treatment to date pt last known alive ] [ Designated as safety issue: No ]
    duration of survival when celecoxib is administered concurrently with radiation in pts with newly diagnosed glioblastoma multiforme


Enrollment: 35
Study Start Date: October 2003
Study Completion Date: May 2006
Primary Completion Date: May 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: radiation therapy
Radiation is standard treatment 6000cGy in 30 fractions. Patients will receive celecoxib 400 mg bid during RT treatment
Other Name: RT
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.
Other Name: Cox2
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: radiation therapy
Radiation is standard treatment 6000cGy in 30 fractions. Patients will receive celecoxib 400 mg bid during RT treatment
Other Name: RT
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.
Other Name: Cox2

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00068770

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612-9497
United States, Georgia
Winship Cancer Institute of Emory University
Atlanta, Georgia, United States, 30322
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore, Maryland, United States, 21231-2410
United States, Massachusetts
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States, 02114-2617
United States, North Carolina
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1030
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Study Chair: Stuart A. Grossman, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Sidney Kimmel Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00068770     History of Changes
Other Study ID Numbers: NABTT-2100 CDR0000328117, U01CA062475, NABTT-2100, JHOC-NABTT-2100
Study First Received: September 10, 2003
Results First Received: November 19, 2012
Last Updated: March 17, 2015
Health Authority: United States: Federal Government

Keywords provided by Sidney Kimmel Comprehensive Cancer Center:
adult glioblastoma
adult giant cell glioblastoma
adult gliosarcoma

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms
Neoplasms by Site
Nervous System Diseases
Anticonvulsants
Celecoxib
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 29, 2015