Clinical trial NCT05179174: The Role of Genetic Mutations and of Circulating mRNAs in Uveal Melanoma
Official title: The Role of Genetic Mutations and of Circulating mRNAs in Uveal Melanoma
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Uveal Melanoma
Keywords: uveal melanoma
GNA11 mutation
GNAQ mutation
micro RNA
Lead sponsor: University of Catania
Sponsor class: OTHER
First posted: 2022-01-05
Enrollment: 102
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with uveal melanoma and controls will be recruited in three centers:

1. the Ophthalmology Clinic of the "Policlinico-Vittorio Emanuele" University Hospital, Catania, Italy
2. the Ophthalmology Clinic of the University of Turin, Italy
3. the Department of General and Pediatric Ophthalmology, Medical University of Lublin, Lublin, Poland

Brief summary: The aim of the study is to identify genetic and epigenetic biomarkers in uveal melanoma, and to evaluate their diagnostic and prognostic role.

In particular, the specific objectives are:

1. to identify the circulating somatic mutations associated with uveal melanoma;
2. to identify the de-regulated miRNAs associated with uveal melanoma;
3. to evaluate the diagnostic and prognostic role of the identified genetic and epigenetic markers;
4. to identify possible therapeutic targets.

Detailed description: This is a prospective, multicentric, case-control study, aimed at studying the gene and epigenetic mechanisms involved in uveal melanoma.

Patients with uveal melanoma, will be enrolled. For each subject included in the study, in a blood sample will be searched the mutations of the GNA11 and GNAQ genes and the expression of the following microRNAs: miR - 506-514 cluster, hsamiR - 592 and hsa - miR - 199a - 5p; the digital PCR droplet system will be used.

The study will not change the diagnostic-therapeutic process adopted in the clinical practice and will have no influence on the clinical management of enrolled patients.

A group of age sex matched controls will be recruited among patients scheduled for cataract surgery.

The sample size was calculated to detect, with a power of 80% and a confidence interval of 95%, a difference of 13.5% between the incidence of mutation of the GNA11 gene in patients with melanoma and healthy controls. (13.5% vs 0%). Overall, at least 51 patients with uveal melanoma and 51 controls will be recruited, for a total of at least 102 subjects.

Eligibility criteria: Inclusion Criteria:

* subjects diagnosed with uveal melanoma
* both sexes
* age ≥ 18 years

Exclusion Criteria:

* a) autoimmune diseases
* b) tumors
* c) kidney diseases
* d) atherosclerosis
* e) subjects undergoing anti-inflammatory therapies.

Primary outcomes:
measure: circulating GNA11 mutation detection through digital droplet PCR
timeFrame: at the diagnosis of uveal melanoma (first visit), through study completion, in an average of 1 year
Secondary outcomes:
measure: micro RNA levels in serum
timeFrame: at the diagnosis of uveal melanoma (first visit), through study completion, in an average of 1 year
Other outcomes:
Locations:
city: Catania
country: Italy
facility: Eye Clinic, Azienda Policlinico San Marco
city: Turin
country: Italy
facility: Eye Clinic University of Turin
city: Lublin
country: Poland
facility: Department of General and Pediatric Ophthalmology, Medical University of Lublin
Study officials:
References:
citation: Krantz BA, Dave N, Komatsubara KM, Marr BP, Carvajal RD. Uveal melanoma: epidemiology, etiology, and treatment of primary disease. Clin Ophthalmol. 2017 Jan 31;11:279-289. doi: 10.2147/OPTH.S89591. eCollection 2017.
citation: Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, Hawkins BS, Hayman JA, Jaiyesimi I, Jampol LM, Kirkwood JM, Koh WJ, Robertson DM, Shaw JM, Straatsma BR, Thoma J; Collaborative Ocular Melanoma Study Group. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol. 2005 Dec;123(12):1639-43. doi: 10.1001/archopht.123.12.1639.
citation: Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, Obenauf AC, Wackernagel W, Green G, Bouvier N, Sozen MM, Baimukanova G, Roy R, Heguy A, Dolgalev I, Khanin R, Busam K, Speicher MR, O'Brien J, Bastian BC. Mutations in GNA11 in uveal melanoma. N Engl J Med. 2010 Dec 2;363(23):2191-9. doi: 10.1056/NEJMoa1000584. Epub 2010 Nov 17.
citation: Falzone L, Romano GL, Salemi R, Bucolo C, Tomasello B, Lupo G, Anfuso CD, Spandidos DA, Libra M, Candido S. Prognostic significance of deregulated microRNAs in uveal melanomas. Mol Med Rep. 2019 Apr;19(4):2599-2610. doi: 10.3892/mmr.2019.9949. Epub 2019 Feb 11.