An Open-Labeled, Extended-Use of XERECEPT (hCRF) for Patients in Studies NTI 0302, 0303, or Other Designated Studies

• Sponsor: Celtic Pharma Development Services (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00226655
• Collaborator: Neurobiological Technologies (Industry)
• Enrollment: 112
• Locations: 32
• Arm: 1
• Duration (Months): 45
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the long-term safety and tolerability of human corticotropin-releasing factor (hCRF), XERECEPT®, in patients requiring dexamethasone (Decadron) to treat peritumoral brain edema. This open-label, extended-use study is open to all patients who participate in either of the blinded studies, NTI 0302, NTI 0303, or other designated studies, including patients who may have discontinued blinded study medication early but completed the protocol-stipulated follow-up periods.

Condition or Disease	Intervention/Treatment	Phase
Brain Edema; Brain Tumor	Drug: hCRF [XERECEPT (corticorelin acetate injection)]	Phase 3

Detailed Description

XERECEPT® is not a potential treatment for cancer, but may reduce the edema associated with tumors and as a result, decrease neurological symptoms.

Study Design

• Study Type: Interventional
• Actual Enrollment: 112 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Labeled, Extended-Use of Human Corticotropin-Releasing Factor (hCRF) Intended for Patients Who Participate in Dexamethasone-Sparing Studies NTI 0302, NTI 0303, or Other Designated Studies
• Study Start Date: Jul 1, 2005
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Apr 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: I All patients will receive hCRF (XERECEPT) 2mg/day	Drug: hCRF [XERECEPT (corticorelin acetate injection)]; 2mg/day; Other Names: hCRF, XERECEPT (corticorelin acetate injection)

Outcome Measures

Primary Outcome Measures

1. Long Term Safety and Tolerability of hCRF [Prospective]

   Number of patients reporting adverse events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participation in and completion of stipulated final follow-up periods for study NTI 0302, NTI 0303, or other designated studies.

• Have a Karnofsky Performance of > 50 at Baseline

• Capable of self-administration of subcutaneous injections twice daily or availability of assistance from caregiver.

• Ability to provide written informed consent or, if unable to provide, have a legal guardian or representative provide written informed consent.

• For women of childbearing potential: a negative serum pregnancy test at Baseline

Exclusion Criteria:

• Concurrent enrollment in any investigational drug or device study, other than NTI 0302, NTI 0303, or other designated studies.

• Systemic steroid use for any indication other than peritumoral brain edema.

• Use or intended use of dexamethasone as an anti-emetic during study.

• Clinical signs and symptoms of cerebral herniation.

• Serious concomitant cardiovascular, pulmonary, renal, gastrointestinal or endocrine metabolic disease which could put the patient at unusual risk during study participation.

• Confounding previous or concurrent neurological disorders that would interfere with adequate clinical evaluation.

• Clinically significant head injury or chronic seizure disorder, if the condition results in functional impairment or is likely to interfere with evaluations.(Maintenance anticonvulsant therapy is allowed)

• Central nervous system (CNS) infection.

• Pregnancy, breastfeeding and/or refusal to practice birth control while in study, for women of childbearing potential.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barrow Neurological Institute	Phoenix	Arizona	United States	85013
2	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92658
3	Stanford University Medical Center	Palo Alto	California	United States	94305
4	UC Davis Medical Center, Division of Medical Oncology	Sacramento	California	United States	95817
5	UC San Diego Cancer Center	San Diego	California	United States	92037
6	University of Colorado Cancer Center	Aurora	Colorado	United States	80045
7	Colorado Neurological Institute Center for Brain & Spinal Tumors	Englewood	Colorado	United States	80113
8	Mayo Clinic	Jacksonville	Florida	United States	32224
9	Cancer Institute of Orlando	Orlando	Florida	United States	32804
10	Moffitt Cancer Center	Tampa	Florida	United States	33612
11	Winship Cancer Institute, Emory University	Atlanta	Georgia	United States	30322
12	Feinberg School of Medicine, Northwestern University	Chicago	Illinois	United States	60611
13	Evanston Northwestern Healthcare	Evanston	Illinois	United States	60201
14	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
15	Hermelin Brain Tumor Center, Henry Ford Hospital	Detroit	Michigan	United States	48202
16	Dent Neurologic Institute	Amherst	New York	United States	14226
17	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
18	Weill Medical College of Cornell University	New York	New York	United States	10021
19	University Hematology Oncology Care, LLC	Cincinnati	Ohio	United States	43210
20	Good Samaritan Hospital	Cincinnati	Ohio	United States	45220
21	The Ohio State University	Columbus	Ohio	United States	43210
22	Oregon Clinic	Portland	Oregon	United States	97210
23	Virginia Mason Clinic	Seattle	Washington	United States	98111
24	University of Wisconsin	Madison	Wisconsin	United States	53792
25	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226-3596
26	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G1ZT
27	CancerCare Manitoba	Winnipeg	Manitoba	Canada	MB R3E 0V9
28	The Moncton Hospital	Moncton	New Brunswick	Canada	E1C 6Z8
29	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia	Canada	B3H 1V7
30	Caner Centre of Southwestern Ontario/ Kingston General Hospital	Kingston	Ontario	Canada	K7L 5P9
31	Ottawa Regional Cancer Center	Ottawa	Ontario	Canada	K1H 1C4
32	Sunnybrook and Women's College Health Sciences Center	Toronto	Ontario	Canada	M4N 3M5

Sponsors and Collaborators

• Celtic Pharma Development Services
• Neurobiological Technologies

Investigators

• Principal Investigator: William Shapiro, MD, Barrow Neurological Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Celtic Pharma Development Services
• ClinicalTrials.gov Identifier: NCT00226655
• Other Study ID Numbers: NTI 0501
• First Posted: Sep 27, 2005
• Last Update Posted: Aug 31, 2012
• Last Verified: Jul 1, 2012

• Keywords provided by Celtic Pharma Development Services: peritumoral brain edema; edema; malignant brain tumor; astrocytoma; brain tumor; dexamethasone; Decadron
• Additional relevant MeSH terms: Brain Neoplasms; Brain Edema; Corticotropin-Releasing Hormone

Study Results

Participant Flow

Recruitment Details	Recruitment started February 2005;
Pre-assignment Detail	Patients rolled-over from previous placebo controlled studies; open label study so no group assignment

Arm/Group Title	hCRF
Arm/Group Description	All patients will receive hCRF (XERECEPT) 2mg/day
Period Title: Overall Study
STARTED	112
COMPLETED	33
NOT COMPLETED	79

Baseline Characteristics

Arm/Group Title	hCRF
Arm/Group Description	All patients will receive hCRF (XERECEPT) 2mg/day
Overall Participants	112
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	101 90.2%
>=65 years	11 9.8%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.4 (11.0)
Sex: Female, Male (Count of Participants)
Female	68 60.7%
Male	44 39.3%
Region of Enrollment (participants) [Number]
United States	101 90.2%
Canada	6 5.4%
Australia	4 3.6%
New Zealand	1 0.9%

Outcome Measures

1. Primary Outcome

Title	Long Term Safety and Tolerability of hCRF
Description	Number of patients reporting adverse events
Time Frame	Prospective

Outcome Measure Data

Analysis Population Description

Intent to Treat

Arm/Group Title	hCRF
Arm/Group Description	hCRF administered 1mg bid subcutaneously
Measure Participants	112
Number [Participants]	111 (4.5) 99.1%

Adverse Events

Arm/Group Title	hCRF
Arm/Group Description	All patients will receive hCRF (XERECEPT) 2mg/day
All Cause Mortality
	hCRF
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	hCRF
	Affected / at Risk (%)	# Events
Total	72/112 (64.3%)
Blood and lymphatic system disorders
Anaemia	1/112 (0.9%)	1
Cardiac disorders
Sinus tachycardia	1/112 (0.9%)	1
Supraventricular tachycardia	1/112 (0.9%)	1
Eye disorders
Blindness	1/112 (0.9%)	1
Gastrointestinal disorders
Diarrhoea	1/112 (0.9%)	1
Vomiting	1/112 (0.9%)	1
General disorders
Asthenia	1/112 (0.9%)	1
Injection site urticaria	2/112 (1.8%)	2
Pain	1/112 (0.9%)	1
Hepatobiliary disorders
Cholecystitis	1/112 (0.9%)	1
Cholelithiasis	1/112 (0.9%)	1
Infections and infestations
Catheter related infection	1/112 (0.9%)	1
Cellulitis	4/112 (3.6%)	4
Clostridial infection	1/112 (0.9%)	1
Lower respiratory tract infection	1/112 (0.9%)	1
Perianal abscess	1/112 (0.9%)	1
Pneumonia	5/112 (4.5%)	5
Rectal abscess	1/112 (0.9%)	1
Sepsis	3/112 (2.7%)	3
Septic shock	2/112 (1.8%)	2
Tooth infection	1/112 (0.9%)	1
Upper respiratory tract infection	1/112 (0.9%)	1
Urinary tract infection	1/112 (0.9%)	1
Injury, poisoning and procedural complications
Fall	4/112 (3.6%)	4
Fibula fracture	1/112 (0.9%)	1
Hip fracture	1/112 (0.9%)	1
Incisional hernia	1/112 (0.9%)	1
Ligament injury	1/112 (0.9%)	1
Rib fracture	2/112 (1.8%)	2
Splenic rupture	1/112 (0.9%)	1
Tibia fracture	1/112 (0.9%)	1
Wound	1/112 (0.9%)	1
Metabolism and nutrition disorders
Gout	1/112 (0.9%)	1
Musculoskeletal and connective tissue disorders
Muscle weakness	1/112 (0.9%)	1
Osteonecrosis	1/112 (0.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Astrocytoma	1/112 (0.9%)	1
Glioblastoma	2/112 (1.8%)	2
Glioblastoma multiforme	5/112 (4.5%)	5
Intracranial tumour haemorrhage	1/112 (0.9%)	1
Lung cancer metastatic	1/112 (0.9%)	1
Lung neoplasm malignant	1/112 (0.9%)	1
Metastases to lung	1/112 (0.9%)	1
Myelodysplastic syndrom	1/112 (0.9%)	1
Neoplasm progression	25/112 (22.3%)	25
Non-small cell lung cancer	1/112 (0.9%)	1
Tumour haemorrhage	1/112 (0.9%)	1
Nervous system disorders
Aphasia	1/112 (0.9%)	1
Brain oedema	1/112 (0.9%)	1
Brain stem haemorrhage	1/112 (0.9%)	1
Cerebral haemorrhage	1/112 (0.9%)	1
Cerebrospinal fistula	1/112 (0.9%)	1
Convulsion	17/112 (15.2%)	17
Encephalopathy	1/112 (0.9%)	1
Haemorrhage intracranial	2/112 (1.8%)	2
Headache	3/112 (2.7%)	3
Status epilepticus	1/112 (0.9%)	1
Syncope	2/112 (1.8%)	2
Psychiatric disorders
Agitation	8/112 (7.1%)	8
Confusional state	1/112 (0.9%)	1
Mental state changes	2/112 (1.8%)	2
Personality change	1/112 (0.9%)	1
Psychotic disorder	2/112 (1.8%)	2
Renal and urinary disorders
Renal failure acute	2/112 (1.8%)	2
Rena tubular necrosis	1/112 (0.9%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/112 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/112 (0.9%)	1
Dyspnoea	1/112 (0.9%)	1
Hypoxia	1/112 (0.9%)	1
Obstructive airways disorder	1/112 (0.9%)	1
Pleural effusion	2/112 (1.8%)	2
Pneumonia aspiration	1/112 (0.9%)	1
Pulmonary embolism	1/112 (0.9%)	1
Respiratory depression	5/112 (4.5%)	5
Respiratory failure	4/112 (3.6%)	4
Skin and subcutaneous tissue disorders
Decubitus ulcer	1/112 (0.9%)	1
Vascular disorders
Deep vein thrombosis	2/112 (1.8%)	2
Hypotension	1/112 (0.9%)	1
Venous thrombosis limb	1/112 (0.9%)	1
Other (Not Including Serious) Adverse Events
	hCRF
	Affected / at Risk (%)	# Events
Total	111/112 (99.1%)
Endocrine disorders
Cushingoid	8/112 (7.1%)	8
Eye disorders
Vision blurred	7/112 (6.3%)	7
Gastrointestinal disorders
Diarrhoea	13/112 (11.6%)	13
Nausea	23/112 (20.5%)	23
Constipation	11/112 (9.8%)	11
Vomiting	12/112 (10.7%)	12
General disorders
Injection site erythema	18/112 (16.1%)	18
Oedema peripheral	13/112 (11.6%)	13
Asthenia	7/112 (6.3%)	7
Fatigue	23/112 (20.5%)	23
Gait disturbance	8/112 (7.1%)	8
Infections and infestations
Pneumonia	9/112 (8%)	9
Upper respiratory tract infection	9/112 (8%)	9
Urinary tract infection	8/112 (7.1%)	8
Injury, poisoning and procedural complications
Contusion	7/112 (6.3%)	7
Fall	12/112 (10.7%)	12
Investigations
Alanine aminotransferase increased	6/112 (5.4%)	6
Weight decreased	6/112 (5.4%)	6
Metabolism and nutrition disorders
Anorexia	6/112 (5.4%)	6
Hyperglycaemia	8/112 (7.1%)	8
Musculoskeletal and connective tissue disorders
Arthralgia	8/112 (7.1%)	8
Back pain	8/112 (7.1%)	8
Muscular weakness	14/112 (12.5%)	14
Musculoskeletal pain	6/112 (5.4%)	6
Pain in extremity	7/112 (6.3%)	7
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
glioblastoma multiforme	8/112 (7.1%)	8
Neoplasm progression	34/112 (30.4%)	34
Nervous system disorders
Aphasia	9/112 (8%)	9
Convulsion	32/112 (28.6%)	32
Dizziness	8/112 (7.1%)	8
Headache	30/112 (26.8%)	30
Hemiparesis	15/112 (13.4%)	15
Hypoaesthesia	10/112 (8.9%)	10
Tremor	7/112 (6.3%)	7
Psychiatric disorders
Confusional state	11/112 (9.8%)	11
Depression	6/112 (5.4%)	6
Insomnia	11/112 (9.8%)	11
Respiratory, thoracic and mediastinal disorders
Cough	8/112 (7.1%)	8
Dyspnoea	8/112 (7.1%)	8
Skin and subcutaneous tissue disorders
Rash	8/112 (7.1%)	8
Skin fragility	7/112 (6.3%)	7
Vascular disorders
Flushing	27/112 (24.1%)	27

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.