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Trial record 84 of 106 for:    PHENYTOIN

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

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ClinicalTrials.gov Identifier: NCT00068770
Recruitment Status : Terminated (EORTC trail showed TMZ & RT conferred significant survivial in this population)
First Posted : September 11, 2003
Results First Posted : March 18, 2015
Last Update Posted : March 18, 2015
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Brain and Central Nervous System Tumors
Interventions Radiation: radiation therapy
Drug: Celecoxib
Enrollment 35
Recruitment Details pts were enrolled on this study from October 2003 to September 2004. Pts were enrolled in an outpatient clinical setting
Pre-assignment Details pts were assigned to an arm at the time of enrollment
Arm/Group Title nonp450 p450
Hide Arm/Group Description

not on p450 inhibitor

celecoxib :

radiation therapy :

on p450 inhibitor

celecoxib :

radiation therapy :

Period Title: Overall Study
Started 13 22
Completed 13 22
Not Completed 0 0
Arm/Group Title p450 ( +EIASD) nonp450 (-EIASD) Total
Hide Arm/Group Description on p450 inhibitor (Patients taking anttiseizure drugs that are known to induce the hepatic drug-metabolizing enzymes - including phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine) 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. Total of all reporting groups
Overall Number of Baseline Participants 22 13 35
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 22 participants 13 participants 35 participants
58  (12) 56  (17) 57  (26)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 22 participants 13 participants 35 participants
Female
8
  36.4%
7
  53.8%
15
  42.9%
Male
14
  63.6%
6
  46.2%
20
  57.1%
Karnofsky Perfomance Status (KPS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 22 participants 13 participants 35 participants
88  (11) 83  (9) 86  (10)
[1]
Measure Description: 100 normal no complaints no disease 90 capable of normal activity few symptoms/disease 80 normal activity with some difficulty some symptoms or signs 70 caring for self not capable of normal activity or work 60 requiring some help can take care of most personal requirements 50 requires help often requires frequent medical care 40 disabled requires special care and help 30 severely disabled hospital admission indicated but no risk of death 20 very ill urgently requiring admission requires supportive measures or treatment 10 moribund rapidly progressive fatal disease processes 0 death
Mini Mental State Exam Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 22 participants 13 participants 35 participants
28  (4) 28  (3) 28  (3)
[1]
Measure Description: The mini–mental state examination (MMSE) is a 30-point questionnaire test used to screen for cognitive impairment. Commonly used to screen for dementia. It is also used to estimate the severity of cognitive impairment and to follow the course of cognitive changes in an individual over time. The MMSE test includes simple questions and problems in a number of areas: the time and place of the test, repeating lists of words, arithmetic such as the serial sevens, language use and comprehension, and basic motor skills. The Higher your score, the higher your function.
Corticosteroid therapy   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 22 participants 13 participants 35 participants
Yes 18 11 29
No 4 2 6
[1]
Measure Description: Patients on corticpsteroid therapy
Prior Surgery   [1] 
Measure Type: Number
Unit of measure:  Participant
Number Analyzed 22 participants 13 participants 35 participants
Craniotomy 21 10 31
Biopsy 1 3 4
[1]
Measure Description: Whether pt had Craniotomy or Biopsy
1.Primary Outcome
Title Effects of Hepatic Enzyme Inducing Drugs Such as Anticonvulsants, on the PK of Celecoxib
Hide Description 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.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description

pts who had PK data for the first dose of celecoxib. observations were excluded if sample was not collected within 12 +/- 2h after taking prior dose, was drawn after dosing on same day or determine to be outlier by dixon's test.

PK data was available for 15 pts in the +EIASD group and 12 pts in the -EIASD group

Arm/Group Title nonp450 p450
Hide Arm/Group Description:

not on p450 inhibitor

celecoxib :

radiation therapy :

on p450 inhibitor

celecoxib :

radiation therapy :

Overall Number of Participants Analyzed 12 15
Geometric Mean (Standard Deviation)
Unit of Measure: (ng/ml)
1752  (550) 1813  (813)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection nonp450, p450
Comments two independent group comparisons
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.82
Comments not adjusted
Method t-test, 2 sided
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.5
Confidence Interval (2-Sided) 95%
1.5 to 5.5
Parameter Dispersion
Type: Standard Deviation
Value: 1
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Overall Survival
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
latest survial data was obtained on May 30, 2006. 31/35 pts had died (89%) 21 in the +EIASD group and 10 in -EIASD group
Arm/Group Title p450 ( +EIASD) nonp450 (-EIASD)
Hide Arm/Group Description:

on p450 inhibitor (Patients taking anttiseizure drugs that are known to induce the hepatic drug-metabolizing enzymes - including phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine)

latest survial data was obtained on May 30, 2006. 31/35 pts had died (89%) 21 in the +EIASD group and 10 in -EIASD group

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.

latest survial data was obtained on May 30, 2006. 31/35 pts had died (89%) 21 in the +EIASD group and 10 in -EIASD group

Overall Number of Participants Analyzed 21 10
Mean (95% Confidence Interval)
Unit of Measure: months
11.5
(8 to 16)
16
(6 to 18)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection p450 ( +EIASD), nonp450 (-EIASD)
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments equivalence analysis
Statistical Test of Hypothesis P-Value 0.11
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
1.1 to 6.3
Parameter Dispersion
Type: Standard Deviation
Value: 1.8
Estimation Comments [Not Specified]
Time Frame until pts progressed off treatment - in this study approximately avg 117 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title P450 ARM Non P450 ARM
Hide Arm/Group Description on p450 inhibitor (Patients taking anttiseizure drugs that are known to induce the hepatic drug-metabolizing enzymes - including phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine) NOT on p450 inhibitor *non P450 ARM (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, Keppra.
All-Cause Mortality
P450 ARM Non P450 ARM
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
P450 ARM Non P450 ARM
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/22 (0.00%)      0/13 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
P450 ARM Non P450 ARM
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   22/22 (100.00%)      13/13 (100.00%)    
Blood and lymphatic system disorders     
Hemoglobin / anemia  1  6/22 (27.27%)  8 2/13 (15.38%)  3
Ear and labyrinth disorders     
Auditory/Hearing  1 [1]  1/22 (4.55%)  2 0/13 (0.00%)  0
vision - blurred vision  1  1/22 (4.55%)  1 0/13 (0.00%)  0
Endocrine disorders     
cushingoid appearance  1  5/22 (22.73%)  6 5/13 (38.46%)  7
Salivary Gland Changes  1  0/22 (0.00%)  0 1/13 (7.69%)  1
Eye disorders     
tearing  1  1/22 (4.55%)  1 1/13 (7.69%)  1
Gastrointestinal disorders     
abdominal pain or cramping  1  1/22 (4.55%)  2 1/13 (7.69%)  1
constipation  1  4/22 (18.18%)  5 1/13 (7.69%)  1
dyspepsia/heartburn  1  4/22 (18.18%)  5 5/13 (38.46%)  5
gastritis  1  1/22 (4.55%)  1 0/13 (0.00%)  0
dry mouth  1  1/22 (4.55%)  1 0/13 (0.00%)  0
nausea  1  5/22 (22.73%)  5 4/13 (30.77%)  4
vomiting  1  1/22 (4.55%)  1 1/13 (7.69%)  1
General disorders     
edema  1  5/22 (22.73%)  6 1/13 (7.69%)  1
fatigue  1  7/22 (31.82%)  8 6/13 (46.15%)  7
Infections and infestations     
infection without neutropenia  1  0/22 (0.00%)  0 1/13 (7.69%)  1
Injury, poisoning and procedural complications     
radiation dermatitis  1  1/22 (4.55%)  1 0/13 (0.00%)  0
Investigations     
weight gain  1  1/22 (4.55%)  1 0/13 (0.00%)  0
alkaline phosphatase  1  5/22 (22.73%)  11 1/13 (7.69%)  1
Platelets  1  3/22 (13.64%)  4 4/13 (30.77%)  5
Activated partial thromboplastin time prolonged  1  1/22 (4.55%)  1 0/13 (0.00%)  0
Asoartate aminotransferase (SGOT)  1  2/22 (9.09%)  2 1/13 (7.69%)  1
alanine aminotransferase (SGPT)  1  3/22 (13.64%)  6 2/13 (15.38%)  5
bilirubin  1  2/22 (9.09%)  2 1/13 (7.69%)  1
white blood count  1  4/22 (18.18%)  6 0/13 (0.00%)  0
Metabolism and nutrition disorders     
anorexia  1  5/22 (22.73%)  5 4/13 (30.77%)  4
dehydration  1  0/22 (0.00%)  0 1/13 (7.69%)  1
Hyperglycemia  1  7/22 (31.82%)  15 2/13 (15.38%)  4
Hyperkalemia  1  1/22 (4.55%)  2 3/13 (23.08%)  3
hypernatremia  1  1/22 (4.55%)  1 0/13 (0.00%)  0
Hypocalcemia  1  3/22 (13.64%)  5 1/13 (7.69%)  1
hypoglycemia  1  2/22 (9.09%)  4 1/13 (7.69%)  1
hypokalemia  1  2/22 (9.09%)  2 0/13 (0.00%)  0
hypomagnesemia  1  2/22 (9.09%)  4 0/13 (0.00%)  0
hyponatremia  1  2/22 (9.09%)  2 0/13 (0.00%)  0
Musculoskeletal and connective tissue disorders     
muscle weakness (not due to neuropathy)  1  4/22 (18.18%)  4 2/13 (15.38%)  2
Nervous system disorders     
ataxia  1  3/22 (13.64%)  3 1/13 (7.69%)  1
Dizziness/lightheadedness  1  5/22 (22.73%)  6 0/13 (0.00%)  0
headache  1  6/22 (27.27%)  7 4/13 (30.77%)  5
memory loss  1  0/22 (0.00%)  0 1/13 (7.69%)  1
neurology -cranial  1  2/22 (9.09%)  2 1/13 (7.69%)  1
neuropathy-motor  1  5/22 (22.73%)  6 0/13 (0.00%)  0
neuropathy - sensory  1  1/22 (4.55%)  1 0/13 (0.00%)  0
Seizure  1  2/22 (9.09%)  2 1/13 (7.69%)  1
speech impairment  1  2/22 (9.09%)  2 1/13 (7.69%)  1
taste disturbance  1  0/22 (0.00%)  0 1/13 (7.69%)  1
tremor  1  2/22 (9.09%)  2 0/13 (0.00%)  0
Photophobia  1 [2]  2/22 (9.09%)  2 0/13 (0.00%)  0
Psychiatric disorders     
confusion  1  5/22 (22.73%)  5 1/13 (7.69%)  1
Insomnia  1  0/22 (0.00%)  0 1/13 (7.69%)  1
depression  1  1/22 (4.55%)  1 1/13 (7.69%)  1
anxiety  1  2/22 (9.09%)  3 2/13 (15.38%)  2
Renal and urinary disorders     
incontinence  1  1/22 (4.55%)  1 0/13 (0.00%)  0
urinary frequency/urgency  1  2/22 (9.09%)  2 0/13 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
dyspnea  1  1/22 (4.55%)  1 1/13 (7.69%)  1
Skin and subcutaneous tissue disorders     
alopecia  1  2/22 (9.09%)  2 3/13 (23.08%)  3
rash/desquamation  1  3/22 (13.64%)  3 3/13 (23.08%)  4
dry skin  1  0/22 (0.00%)  0 1/13 (7.69%)  1
Vascular disorders     
Hypotension  1  0/22 (0.00%)  0 1/13 (7.69%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (2.0)
[1]
hearing loss
[2]
Neurology-Other
Study ended early when results from another study became available documenting Temozolomide (TMZ) and radiation improved survival, we felt it was unethical to continue this study, our study did not include TMZ.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Dr. Stuart A Grossman
Organization: Johns Hopkins University
Phone: 410-955-3657
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT00068770     History of Changes
Other Study ID Numbers: NABTT-2100 CDR0000328117
U01CA062475 ( U.S. NIH Grant/Contract )
NABTT-2100
JHOC-NABTT-2100
First Submitted: September 10, 2003
First Posted: September 11, 2003
Results First Submitted: November 19, 2012
Results First Posted: March 18, 2015
Last Update Posted: March 18, 2015