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 |
| Protocol serial number | 155/2006 |
| Sponsor | VU University Medical Centre (The Netherlands) |
| Funder | VU University Medical Center (The Netherlands) |
- 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
Scientific
VU University Medical Center
Department of Pulmonary Diseases
P.O. Box 7057
Amsterdam
1007 MB
Netherlands
| Phone | +31 (0)20 444 4782 |
|---|---|
| a.boonstra@vumc.nl |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Phase II study, open-labelled trial |
| Secondary study design | Single-centre |
| Scientific title | |
| Study objectives | As 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) studied | Sclerosis-associated Pulmonary Arterial Hypertension (SScPAH) |
| Intervention | All 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 type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Cetuximab |
| Primary outcome measure(s) |
Safety: 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). |
| Key secondary outcome measure(s) |
Efficacy: 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). |
| Completion date | 01/01/2010 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Sex | All |
| Target sample size at registration | 20 |
| Key inclusion criteria | A 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 criteria | A 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 enrolment | 01/01/2007 |
| Date of final enrolment | 01/01/2010 |
Locations
Countries of recruitment
- Netherlands
Study participating centre
VU University Medical Center
Amsterdam
1007 MB
Netherlands
1007 MB
Netherlands
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Not provided at time of registration |
| IPD sharing plan |
