The Role of Genetic Mutations and of Circulating mRNAs in Uveal Melanoma

Uveal Melanoma Clinical Trial

Official title:

The Role of Genetic Mutations and of Circulating mRNAs in Uveal Melanoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05179174
• Other study ID #: 71/2020/PO
• Status: Recruiting
• Start date: April 20, 2021
• Est. completion date: December 2023

Study information

• Verified date: December 2021
• Source: University of Catania
• Contact: Antonio Longo, MD PhD
• Phone: +393460131548
• Email: antlongo[@]unict.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 102
• Est. completion date: December 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Melanoma
• Uveal Melanoma
• Uveal Neoplasms

Intervention

Genetic:
• blood sample examination
droplet digital PCR in blood sample for research of mutations of GNA11 and GNAQ genes and the following microRNAs: miR - 506-514 cluster, hsamiR - 592 and hsa - miR - 199a - 5p.

Locations

Country	Name	City	State
Italy	Eye Clinic, Azienda Policlinico San Marco	Catania
Italy	Eye Clinic University of Turin	Turin
Poland	Department of General and Pediatric Ophthalmology, Medical University of Lublin	Lublin

Sponsors (1)

Lead Sponsor	Collaborator
University of Catania

Countries where clinical trial is conducted

Italy,  Poland, 

References & Publications (4)

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. — View 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. — View 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. Review. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	circulating GNA11 mutation detection through digital droplet PCR	the incidence of GNA11 mutations in uveal melanoma patients and in controls	at the diagnosis of uveal melanoma (first visit), through study completion, in an average of 1 year
Secondary	micro RNA levels in serum	the expression levels of circulating miRNAs (miR - 506-514 cluster, hsamiR - 592 and hsa - miR - 199a - 5p) in uveal melanoma patients and in controls	at the diagnosis of uveal melanoma (first visit), through study completion, in an average of 1 year