The first objective is to evaluate the safety of cetuximab in patients with scleroderma associated PAH. The secondary objective is to assess efficacy.
ID
Source
Brief title
Condition
- Heart failures
- Connective tissue disorders (excl congenital)
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To describe the safety of cetuximab in scleroderma associated PAH.
Secondary outcome
To explore the efficacy of cetuximab in terms of: stroke volume, 6 minute walk
test, changes on HRCT, changes in nailfold microcirculation, changes in
molecular parameters (NT-proBNP)
Background summary
The prognosis of Pulmonary arterial hypertension (PAH) associated with
scleroderma continues to be poor with a 3-year survival of 56%, despite
implementation of new therapies. Therefore, new therapeutic strategies are
warranted. One such strategy could be pharmacological inhibition of the
epidermal growth factor receptor (EGFR), as recent research shows that the EGFR
plays an important role in the pathogenesis of both PAH and scleroderma. The
chimeric monoclonal antibody Cetuximab (ErbituxÒ) against the extracellular
domain of the EGFR is registered for the treatment of colorectal cancer and
SCCHN. In this study, we evaluate the use of Cetuximab in the treatment of
scleroderma associated PAH.
Study objective
The first objective is to evaluate the safety of cetuximab in patients with
scleroderma associated PAH. The secondary objective is to assess efficacy.
Study design
This will be a phase II study, open-labelled, in one hospital in the
Netherlands. The first phase consists of the successive enrollment of three
patients. After evaluation, enrollment will be enhanced to a total number of 20
patients.
Intervention
Cetuximab, loading dose 400 mg/m2 week 1. week 2 t/m week 11 maintainance dose
of 250 mg/m2.
Study burden and risks
Number of institutional visits: 15. Number of physical examinations 15. Number
of blood samples: 15. Other invasive investigations: Right heart
catheterization 1x; skin biopsy 2x.
Risks associated with investigations: risks associated with right heart
catheterization (1:2000 major complications) and skin biopsies. Major risks
associated with investigational product: 5% allergic side effects; severe
infusion reactions 3% of subjects, fatal outcome < 1 in 1000; 5%
conjunctivitis; 80% skin toxicity of which 15% severe (CTCAE Grade 3); 25 out
of 100 patients report dyspnoea.
SSc-PAH is a severe disease with a poor prognosis, but this intervention
methods may provide advantages over existing therapy in terms of efficacy and
treatment burden compared with existing therapy.
De Boelelaan 1117
1081 HV Amsterdam
NL
De Boelelaan 1117
1081 HV Amsterdam
NL
Listed location countries
Age
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. PAH with a mean PAP of above 25 mmHg measured during rest.
4. PVR above 300 dynes
5. TLC > 70 %
6. NYHA class III and/or 6 Minute Walk Test < 80% predicted
7.Conventional PAH treatment and/or bosentan and/or sildenafil treatment
8. Stability on medication during the previous 3 months (defined as stable or decrease of 6 MWT after 3 months of treatment).
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 >/= 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 hematologic function defined by an absolute neutrophil count < 1,500/mm3, platelet count < 80.000/mm3 and hemoblobin level of < 9 g/dL
14.-Inadequate hepatic function defined by a total bilirubin level 1.5 times the upper limit of normal (ULN) and ASAT levels 2.5 times ULN
15. Inadequate renal function defined by a serum creatinine level > 1,5 times ULN (alternative: Cockroft <50 ml/min).
16. Substances that inhibit CYP3A4 activity, such as rifampicin, phenytoin, ketoconazole, itraconazole (see section 6.4.5)
17. Severe interstitial fibrosis on HRCT
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-002081-19-NL |
| CCMO | NL12242.029.06 |