The effects of epidermal growth factor receptor inhibition on pulmonary arterial hypertension associated with systemic sclerosis

ISRCTN ISRCTN75611179
DOI https://doi.org/10.1186/ISRCTN75611179
Secondary identifying numbers 155/2006
Submission date
01/02/2007
Registration date
01/02/2007
Last edited
06/02/2007
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr A Boonstra
Scientific

VU University Medical Center
Department of Pulmonary Diseases
P.O. Box 7057
Amsterdam
1007 MB
Netherlands

Phone +31 (0)20 444 4782
Email a.boonstra@vumc.nl

Study information

Study designPhase II study, open-labelled trial
Primary study designInterventional
Secondary study designSingle-centre
Study setting(s)Other
Study typeTreatment
Scientific title
Study objectivesAs Epidermal Growth Factor Receptor (EGFR) plays a role in pathogenesis of both pulmonary arterial hypertension and systemic sclerosis, EGFR inhibition will lead to beneficial effects in disease course.
Ethics approval(s)Approval received from the Medical Ethics Review Committee of VU University Medical Centre.
Health condition(s) or problem(s) studiedSclerosis-associated Pulmonary Arterial Hypertension (SScPAH)
InterventionAll participants will receive cetuximab at a loading dose of 400 mg/m^2 in week one, followed by a weekly dose of 250 mg/m^2 starting from week two, up to a total of 12 weeks.
Intervention typeDrug
Pharmaceutical study type(s)
PhasePhase II
Drug / device / biological / vaccine name(s)Cetuximab
Primary outcome measureSafety: recorded by assessment and documentation in the Case Report Form (CRF) file of adverse events and toxicity (physical examination [with special attention to skin toxicity], laboratory data) at pre-treatment, treatment visits (week one to 12), and follow-up (six months, 12 months).
Secondary outcome measuresEfficacy: measured by effects on six minute walk test, stroke volume, changes in High Resolution Computed Tomography (HRCT), N-Terminal B-type Natriuretic Peptide (NT-pro-BNP).
Overall study start date01/01/2007
Completion date01/01/2010

Eligibility

Participant type(s)Patient
Age groupNot Specified
SexBoth
Target number of participants20
Key inclusion criteriaA subject is eligible for inclusion in this study only if all of the following criteria apply:
1. Written informed consent
2. Systemic sclerosis
3. Pulmonary Arterial Hypertension (PAH) with a mean Pulmonary Arterial Pressure (PAP) of above 25 mmHg measured during rest
4. Pulmonary Vascular Resistance (PVR) above 300 dynes
5. Total Lung Capacity (TLC) more than 70%
6. New York Heart Association (NYHA) class III and/or six-Minute Walk Test (6-MWT) less than 80% predicted
7.Conventional PAH treatment and/or bosentan and/or sildenafil treatment
8. Stability on medication during the previous three months (defined as stable or decrease of 6-MWT after three months of treatment)
Key exclusion criteriaA subject will be excluded from this study in case of the following criteria:
1. Left ventricular dysfunction
2. Valvular heart disease
3. Pericardial constriction
4. Wedge pressure more than or equal to 15 mmHg
5. Chronic thromboembolic pulmonary hypertension
6. Uncontrolled sleep apnea
7. History of malignancies
8. Overt right heart failure
9. History or presence of skin ulcerations
10. Women Of Child-Bearing potential (WOCB) who are unwilling or unable to use contraceptives
11. Sexually active fertile man not using effective birth control if their partners are WOCB
12. Severe abnormality of the cornea
13. Inadequate haematologic function defined by an absolute neutrophil count less than 1,500/mm^3, platelet count less than 80,000/mm^3 and haemoblobin level of less than 9 g/dL
14. Inadequate hepatic function defined by a total bilirubin level 1.5 times the Upper Limit of Normal (ULN) and ASpartate AminoTransferase (ASAT) levels 2.5 times ULN
15. Inadequate renal function defined by a serum creatinine level more than 1.5 times ULN (alternative: Cockroft less than 50 ml/min)
16. Substances that inhibit CYP3A4 activity, such as rifampicin, phenytoin, ketoconazole, itraconazole
Date of first enrolment01/01/2007
Date of final enrolment01/01/2010

Locations

Countries of recruitment

  • Netherlands

Study participating centre

VU University Medical Center
Amsterdam
1007 MB
Netherlands

Sponsor information

VU University Medical Centre (The Netherlands)
Hospital/treatment centre

Van der Boechorststraat 7
Amsterdam
1081 BT
Netherlands

Website http://www.vumc.nl/english/#http://www.vumc.nl/english/
ROR logo "ROR" https://ror.org/00q6h8f30

Funders

Funder type

Hospital/treatment centre

VU University Medical Center (The Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan