Trial Outcomes & Findings for Celecoxib in Patients With Newly Diagnosed GBM Who Are Receiving Anticonvulsant Drugs and Undergoing RT (NCT NCT00068770)

Last Updated: 2015-03-18

Results Overview

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

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

35 participants

Primary outcome timeframe

First dose of celecoxib through completion of radiation, 6 weeks.

Results posted on

2015-03-18

Participant Flow

pts were enrolled on this study from October 2003 to September 2004. Pts were enrolled in an outpatient clinical setting

pts were assigned to an arm at the time of enrollment

Participant milestones

Participant milestones
Measure	nonp450 not on p450 inhibitor celecoxib : radiation therapy :	p450 on p450 inhibitor celecoxib : radiation therapy :
Overall Study STARTED	13	22
Overall Study COMPLETED	13	22
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	p450 ( +EIASD) n=22 Participants on p450 inhibitor (Patients taking anttiseizure drugs that are known to induce the hepatic drug-metabolizing enzymes - including phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine)	nonp450 (-EIASD) n=13 Participants 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 n=35 Participants Total of all reporting groups
Age, Continuous	58 years STANDARD_DEVIATION 12 • n=5 Participants	56 years STANDARD_DEVIATION 17 • n=7 Participants	57 years STANDARD_DEVIATION 26 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	7 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	6 Participants n=7 Participants	20 Participants n=5 Participants
Karnofsky Perfomance Status (KPS)	88 scores on a scale STANDARD_DEVIATION 11 • n=5 Participants	83 scores on a scale STANDARD_DEVIATION 9 • n=7 Participants	86 scores on a scale STANDARD_DEVIATION 10 • n=5 Participants
Mini Mental State Exam Score	28 scores on a scale STANDARD_DEVIATION 4 • n=5 Participants	28 scores on a scale STANDARD_DEVIATION 3 • n=7 Participants	28 scores on a scale STANDARD_DEVIATION 3 • n=5 Participants
Corticosteroid therapy Yes	18 Participants n=5 Participants	11 Participants n=7 Participants	29 Participants n=5 Participants
Corticosteroid therapy No	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Prior Surgery Craniotomy	21 Participant n=5 Participants	10 Participant n=7 Participants	31 Participant n=5 Participants
Prior Surgery Biopsy	1 Participant n=5 Participants	3 Participant n=7 Participants	4 Participant n=5 Participants

PRIMARY outcome

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

Population: 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

Outcome measures

Outcome measures
Measure	nonp450 n=12 Participants not on p450 inhibitor celecoxib : radiation therapy :	p450 n=15 Participants on p450 inhibitor celecoxib : radiation therapy :
Effects of Hepatic Enzyme Inducing Drugs Such as Anticonvulsants, on the PK of Celecoxib	1752 (ng/ml) Standard Deviation 550	1813 (ng/ml) Standard Deviation 813

SECONDARY outcome

Timeframe: date pt started treatment to date pt last known alive

Population: 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

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

Outcome measures

Outcome measures
Measure	nonp450 n=21 Participants not on p450 inhibitor celecoxib : radiation therapy :	p450 n=10 Participants on p450 inhibitor celecoxib : radiation therapy :
Overall Survival	11.5 months Interval 8.0 to 16.0	16 months Interval 6.0 to 18.0

Adverse Events

P450 ARM

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Non P450 ARM

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Stuart A Grossman

Johns Hopkins University

Phone: 410-955-3657

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	P450 ARM n=22 participants at risk on p450 inhibitor (Patients taking anttiseizure drugs that are known to induce the hepatic drug-metabolizing enzymes - including phenytoin, carbamazepine, phenobarbital, primidone and oxcarbazepine)	Non P450 ARM n=13 participants at risk 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.
Gastrointestinal disorders abdominal pain or cramping	4.5% 1/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Skin and subcutaneous tissue disorders alopecia	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	23.1% 3/13 • Number of events 3 • until pts progressed off treatment - in this study approximately avg 117 days.
Metabolism and nutrition disorders anorexia	22.7% 5/22 • Number of events 5 • until pts progressed off treatment - in this study approximately avg 117 days.	30.8% 4/13 • Number of events 4 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders ataxia	13.6% 3/22 • Number of events 3 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Ear and labyrinth disorders Auditory/Hearing	4.5% 1/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Psychiatric disorders confusion	22.7% 5/22 • Number of events 5 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Gastrointestinal disorders constipation	18.2% 4/22 • Number of events 5 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Endocrine disorders cushingoid appearance	22.7% 5/22 • Number of events 6 • until pts progressed off treatment - in this study approximately avg 117 days.	38.5% 5/13 • Number of events 7 • until pts progressed off treatment - in this study approximately avg 117 days.
Metabolism and nutrition disorders dehydration	0.00% 0/22 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Skin and subcutaneous tissue disorders rash/desquamation	13.6% 3/22 • Number of events 3 • until pts progressed off treatment - in this study approximately avg 117 days.	23.1% 3/13 • Number of events 4 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders Dizziness/lightheadedness	22.7% 5/22 • Number of events 6 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Skin and subcutaneous tissue disorders dry skin	0.00% 0/22 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Gastrointestinal disorders dyspepsia/heartburn	18.2% 4/22 • Number of events 5 • until pts progressed off treatment - in this study approximately avg 117 days.	38.5% 5/13 • Number of events 5 • until pts progressed off treatment - in this study approximately avg 117 days.
Respiratory, thoracic and mediastinal disorders dyspnea	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
General disorders edema	22.7% 5/22 • Number of events 6 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
General disorders fatigue	31.8% 7/22 • Number of events 8 • until pts progressed off treatment - in this study approximately avg 117 days.	46.2% 6/13 • Number of events 7 • until pts progressed off treatment - in this study approximately avg 117 days.
Gastrointestinal disorders gastritis	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Gastrointestinal disorders dry mouth	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders headache	27.3% 6/22 • Number of events 7 • until pts progressed off treatment - in this study approximately avg 117 days.	30.8% 4/13 • Number of events 5 • until pts progressed off treatment - in this study approximately avg 117 days.
Vascular disorders Hypotension	0.00% 0/22 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Renal and urinary disorders incontinence	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Infections and infestations infection without neutropenia	0.00% 0/22 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Psychiatric disorders Insomnia	0.00% 0/22 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders memory loss	0.00% 0/22 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Psychiatric disorders depression	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Psychiatric disorders anxiety	9.1% 2/22 • Number of events 3 • until pts progressed off treatment - in this study approximately avg 117 days.	15.4% 2/13 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.
Musculoskeletal and connective tissue disorders muscle weakness (not due to neuropathy)	18.2% 4/22 • Number of events 4 • until pts progressed off treatment - in this study approximately avg 117 days.	15.4% 2/13 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.
Gastrointestinal disorders nausea	22.7% 5/22 • Number of events 5 • until pts progressed off treatment - in this study approximately avg 117 days.	30.8% 4/13 • Number of events 4 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders neurology -cranial	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders neuropathy-motor	22.7% 5/22 • Number of events 6 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders neuropathy - sensory	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Endocrine disorders Salivary Gland Changes	0.00% 0/22 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Injury, poisoning and procedural complications radiation dermatitis	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders Seizure	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders speech impairment	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders taste disturbance	0.00% 0/22 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Eye disorders tearing	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders tremor	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Renal and urinary disorders urinary frequency/urgency	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Ear and labyrinth disorders vision - blurred vision	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Gastrointestinal disorders vomiting	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Investigations weight gain	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Investigations alkaline phosphatase	22.7% 5/22 • Number of events 11 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Blood and lymphatic system disorders Hemoglobin / anemia	27.3% 6/22 • Number of events 8 • until pts progressed off treatment - in this study approximately avg 117 days.	15.4% 2/13 • Number of events 3 • until pts progressed off treatment - in this study approximately avg 117 days.
Investigations Platelets	13.6% 3/22 • Number of events 4 • until pts progressed off treatment - in this study approximately avg 117 days.	30.8% 4/13 • Number of events 5 • until pts progressed off treatment - in this study approximately avg 117 days.
Metabolism and nutrition disorders Hyperglycemia	31.8% 7/22 • Number of events 15 • until pts progressed off treatment - in this study approximately avg 117 days.	15.4% 2/13 • Number of events 4 • until pts progressed off treatment - in this study approximately avg 117 days.
Investigations Activated partial thromboplastin time prolonged	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Investigations Asoartate aminotransferase (SGOT)	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Investigations alanine aminotransferase (SGPT)	13.6% 3/22 • Number of events 6 • until pts progressed off treatment - in this study approximately avg 117 days.	15.4% 2/13 • Number of events 5 • until pts progressed off treatment - in this study approximately avg 117 days.
Investigations bilirubin	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Investigations white blood count	18.2% 4/22 • Number of events 6 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Nervous system disorders Photophobia	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Metabolism and nutrition disorders Hyperkalemia	4.5% 1/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	23.1% 3/13 • Number of events 3 • until pts progressed off treatment - in this study approximately avg 117 days.
Metabolism and nutrition disorders hypernatremia	4.5% 1/22 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Metabolism and nutrition disorders Hypocalcemia	13.6% 3/22 • Number of events 5 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Metabolism and nutrition disorders hypoglycemia	9.1% 2/22 • Number of events 4 • until pts progressed off treatment - in this study approximately avg 117 days.	7.7% 1/13 • Number of events 1 • until pts progressed off treatment - in this study approximately avg 117 days.
Metabolism and nutrition disorders hypokalemia	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Metabolism and nutrition disorders hypomagnesemia	9.1% 2/22 • Number of events 4 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.
Metabolism and nutrition disorders hyponatremia	9.1% 2/22 • Number of events 2 • until pts progressed off treatment - in this study approximately avg 117 days.	0.00% 0/13 • until pts progressed off treatment - in this study approximately avg 117 days.