Clinical trial NCT04705389: SerUM Markers in MERkel Cell Carcinoma Patients: a Longitudinal moniTorIng Study for optiMization of European Guidelines
Official title: SerUM Markers in MERkel Cell Carcinoma Patients: a Longitudinal moniTorIng Study for optiMization of European Guidelines
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Merkel Cell Carcinoma
Keywords: biomarker
monitoring
prognosis
merkel cell polyomavirus
miR375
T-antigen antibodies
Lead sponsor: University Hospital, Tours
Sponsor class: OTHER
Collaborators: name: European Academy of Dermatology and Venerology
First posted: 2021-01-12
Enrollment: 150
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: Merkel cell carcinoma (MCC) is a rare aggressive skin carcinoma. Approximately 80% of MCC are related to the Merkel Cell Polyomavirus (MCPyV). Although rates of relapse are high, the follow-up strategy lacks consensus. Patients are usually assessed clinically every 3 to 6 months for the first 2-3 years, and every 6 to 12 months thereafter. In the European guidelines, patients with early stages are monitored with clinical examination and ultrasonography of lymph nodes, while whole-body imaging is optional in patients with stage III disease, on a yearly basis for 5 years. Such strategy may prevent the diagnosis of infra-clinical recurrences, whereas patients could still be treated with surgery or radiation therapy. Until 2017, patients with advanced disease were treated with chemotherapies, with no long-term benefit. Immunotherapies with PD-1/PD-L1 inhibitors currently allow durable responses in 50% of such patients. This major change in the management of MCC patients argues for a follow-up strategy that would allow early diagnosis of infra-clinical metastases, when tumoral burden is still low. Given that all patients cannot be monitored by systematic regular imaging, additional non-invasive tools are needed. Blood-based biomarkers as a surrogate of tumor burden are advantageous as they can be repeated over time, providing guidance on when imaging is necessary. The study aims to assess two blood biomarkers, MCPyV T-Ag antibodies and cell-free miR-375, in a prospective fashion from baseline diagnosis, in a cohort of 150 European MCC patients


Eligibility criteria: Inclusion Criteria:

* Patients with a " de novo " diagnosis of MCC, confirmed on histological criteria (neuroendocrine morphology, CK20 staining and/or neuroendocrine and/or SATB2 staining, exclusion of differential diagnosis)
* ≥ 18 years of age
* Written informed consent obtained from the participant

Exclusion Criteria:

* Patients following any measures of legal presentation
* Pregnancy or breastfeeding

Primary outcomes:
measure: To assess the diagnostic performances of two blood biomarkers (T-antigen antibodies and miR375) in detecting disease recurrence during follow up of patients with Merkel Cell Carcinoma
timeFrame: 12 months
Secondary outcomes:
measure: To assess if these two blood biomarkers (T-antigen antibodies and miR375) assessed at baseline are associated with prognosis and response to treatments.
timeFrame: 12 months
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Department of Dermatology, Medical University of Vienna
city: Helsinki
country: Finland
facility: University Hospital of Helsinki, Finland
city: Tours
country: France
facility: Dermatology Dept, Hospital University of Tours
city: Essen
country: Germany
facility: Translational Skin Cancer Research
city: Naples
country: Italy
facility: National Tumour Institute "Fondazione G. Pascale" Unit of Melanoma - Cancer Immunotherapy and Innovative therapy
city: Maastricht
country: Netherlands
facility: Academic Hospital of Maastricht
city: Bucharest
country: Romania
facility: Department of Dermatology, Carol Davila University of Medicine and Pharmacy
city: Gothenburg
country: Sweden
facility: Skin Cancer and Surgery Center, Sahlgrenska University Hospital
city: Ankara
country: Turkey
facility: Department of Dermatology, Başkent University Faculty of Medicine
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
Study officials:
affiliation: University Hospital, Tours
name: Mahtab SAMIMI, MD-PhD
role: STUDY_DIRECTOR
References:
citation: Fan K, Ritter C, Nghiem P, Blom A, Verhaegen ME, Dlugosz A, Odum N, Woetmann A, Tothill RW, Hicks RJ, Sand M, Schrama D, Schadendorf D, Ugurel S, Becker JC. Circulating Cell-Free miR-375 as Surrogate Marker of Tumor Burden in Merkel Cell Carcinoma. Clin Cancer Res. 2018 Dec 1;24(23):5873-5882. doi: 10.1158/1078-0432.CCR-18-1184. Epub 2018 Jul 30.
citation: Kervarrec T, Tallet A, Miquelestorena-Standley E, Houben R, Schrama D, Gambichler T, Berthon P, Le Corre Y, Hainaut-Wierzbicka E, Aubin F, Bens G, Tabareau-Delalande F, Beneton N, Fromont G, Arbion F, Leteurtre E, Touze A, Samimi M, Guyetant S. Diagnostic accuracy of a panel of immunohistochemical and molecular markers to distinguish Merkel cell carcinoma from other neuroendocrine carcinomas. Mod Pathol. 2019 Apr;32(4):499-510. doi: 10.1038/s41379-018-0155-y. Epub 2018 Oct 22.
citation: Paulson KG, Lewis CW, Redman MW, Simonson WT, Lisberg A, Ritter D, Morishima C, Hutchinson K, Mudgistratova L, Blom A, Iyer J, Moshiri AS, Tarabadkar ES, Carter JJ, Bhatia S, Kawasumi M, Galloway DA, Wener MH, Nghiem P. Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study. Cancer. 2017 Apr 15;123(8):1464-1474. doi: 10.1002/cncr.30475. Epub 2016 Dec 7.
citation: Samimi M, Molet L, Fleury M, Laude H, Carlotti A, Gardair C, Baudin M, Gouguet L, Maubec E, Avenel-Audran M, Esteve E, Wierzbicka-Hainaut E, Beneton N, Aubin F, Rozenberg F, Dupin N, Avril MF, Lorette G, Guyetant S, Coursaget P, Touze A. Prognostic value of antibodies to Merkel cell polyomavirus T antigens and VP1 protein in patients with Merkel cell carcinoma. Br J Dermatol. 2016 Apr;174(4):813-22. doi: 10.1111/bjd.14313. Epub 2016 Feb 3.