iSITE: Investigation of Somatic Alterations in Tumours of the Eye

NCT06861647 | Completed

• 1 other identifier: 242945
• Study Type: observational
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

Modern DNA sequencing technologies enable researchers to identify mutations that have been acquired during the lifetime of patients (somatic mutations). Some of these somatic mutations occur in cancer genes and increase the risk of developing cancer. This study will apply such sequencing technologies to cancers of the eye (ocular melanoma) in order to identify mutations associated with these cancers. Sequencing patients at different stages of their disease will allows us to build a timeline of the order of mutations that occur at each stage. This information can be used to understand how these cancers develop, spread (metastasise) and respond to treatment. Furthermore, the study will look at which of these somatic mutations are present in the blood, by collecting blood samples and sequencing fragments of DNA which have been released by tumours into the bloodstream (circulating tumour DNA, ctDNA). This will determine whether ctDNA can be used as a way of monitoring mutations present in the tumour. This study will provide much needed insight into a rare and understudied cancer type, with the long-term aim of improving the survival of patients by identifying key mutations to develop novel therapies against.

Conditions

Somatic Mutation; Ocular Melanoma

Outcome Measures

Primary Outcomes (3)

• Measuring what somatic mutations are acquired during development and metastases in uveal melanomas and conjunctival melanomas.

  Tracking the mutational changes of a tumour in the same patient over time will allow the investigators to determine the order in which mutations are acquired and therefore provide insight into their roles in disease biology. Most studies have sequenced primary tumours and metastatic tumours from different patients. This makes comparison between the two groups of tumours difficult due to the presence of mutations specific to patients, but not necessarily important for cancer development. To determine the relevance of these commonly altered genes, a larger number of paired tumours will be sequenced.

  6.5 years

• Measure whether tumour intratumoural heterogeneity (the mixture of different tumour cell types within one tumour) is associated with a poor clinical outcome.

  There is emerging evidence that diverse populations of cells exist in different regions within a single tumour (intratumoural heterogeneity) in uveal melanoma. This is a result of the development of different groups of mutations (subclones) which evolve - a reflection of the adaptive nature of cancer over time. Intratumoural heterogeneity has been linked with poor clinical outcomes in other cancer types. This study will determine what subclones exist, and to what extent they are associated with poor clinical outcomes in uveal and conjunctival melanoma. Samples at different time points from the same patient, and samples across different regions within the same tumour, will undergo sequencing of the whole genome, whole exome or targeted sets of cancer genes. This will allow identification of somatic alterations from base substitutions to larger genome rearrangements, and comparisons to be made between the burden and type of somatic alternations identified.

  6.5 years

• Measuring the burden and prevalence of somatic mutations in normal and cancer samples of tumours of the eye

  Samples at different time points from the same patient, and samples across different regions within the same tumour, will undergo sequencing of the whole genome, whole exome or targeted sets of cancer genes. This will allow identification of somatic alterations from base substitutions to larger genome rearrangements, and comparisons to be made between the burden and type of somatic alterations identified.

  6.5 years

Secondary Outcomes (1)

• Do mutations detected in circulating tumour DNA reflect the somatic mutations found within the tumour and the effectiveness of this measure as a means of monitoring tumour evolution, and disease progression.

  6.5 years

Study Arms (4)

A (Primary uveal melanoma)

Prospective collection, primary uveal melanoma. If patients have previously collected samples, consent will be requested to also obtain these samples.

Other: sample collection; Other: Discussing study/seeking consent; Other: Completion of Study Questionnaire; Other: Blood Sample

B1 (Metastatic uveal melanoma)

Prospective collection, metastatic uveal melanoma. If patients have previously collected samples, consent will be requested to also obtain these samples.

Other: sample collection; Other: Discussing study/seeking consent; Other: Completion of Study Questionnaire; Other: Blood Sample

B2 (Metastatic uveal melanoma, precollected only)

Previously collected and stored tissue samples, retrospective collection only, metastatic uveal melanoma

C (Conjunctival melanoma)

Previously collected and stored tissue samples, retrospective collection only, metastatic conjunctival melanoma ,

Interventions

Discussing study/seeking consent OTHER

An NHS or CRN staff member will inform patients of the nature and objectives of the study, go through the participant information sheet, highlighting possible risks associated with their participation and reiterate the voluntary nature of this study. Patients will be given opportunities to ask questions pertaining to the study. If the potential participant is still interested in taking part, written informed consent for the study will then be received and a copy of the informed consent will be given to the participant to keep.

A (Primary uveal melanoma); B1 (Metastatic uveal melanoma)

Completion of Study Questionnaire OTHER

Patient will complete in own time. To take place in a routine outpatient clinic appointment

A (Primary uveal melanoma); B1 (Metastatic uveal melanoma)

Blood Sample OTHER

To take place in an outpatient clinic.

A (Primary uveal melanoma); B1 (Metastatic uveal melanoma)

sample collection OTHER

sample collection of surplus samples not needed for diagnostic or pathological requirements

A (Primary uveal melanoma); B1 (Metastatic uveal melanoma)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This research study will include participants with primary uveal melanoma and/or metastatic uveal melanoma and participants with conjunctival melanoma. A member of the participant's clinical care team, a research nurse or member of the Clinical Research Network (CRN) will have access to patient records to identify potential participants and check whether they meet the eligibility criteria and if there are previously collected available samples. Patients who have, and those who have not, previously given written consent for their samples that were obtained during standard procedures of treatment, to be used in research, will be eligible.

You may qualify if:

• Patients ≥ 18 years of age or over
• Histological diagnosis of primary or recurrent/metastatic ocular melanoma\*.
• Healthy eye, blood and liver samples stored in biobanks with consent for use in research.
• \*With the exception of primary uveal melanoma where a clinical diagnosis is sufficient. A diagnostic accuracy of \>99% is achieved using the combination of ophthalmoscopy (examination of the back of the eye), fundus photography (photograph of the back of the eye) and an eye ultrasound.

You may not qualify if:

• Patients \< 18 years of age

Sponsors & Collaborators

• Moorfields Eye Hospital NHS Foundation Trust: collaborator
• St. Bartholomew's Hospital: collaborator
• The Wellcome Sanger Institute: lead

Study Sites (1)

Wellcome Sanger Institute

Cambridge, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Uveal melanoma tissue samples from pathology archives and/or NHS REC approved research tissue banks. Eye tumour tissue biopsies, surgical waste material from eye tumour operations, vitreous fluid and blood samples. Healthy eye, blood and liver samples.

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Specimen Handling; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Punctures; Surgical Procedures, Operative

Study Officials

• Pui Ying Chan

  Wellcome Sanger Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 7, 2025
• First Posted: March 6, 2025
• Study Start: March 25, 2019
• Primary Completion: February 7, 2022
• Study Completion: February 28, 2025
• Last Updated: April 1, 2026

Record last verified: 2025-07

Locations

GB (1)