iSITE: Investigation of Somatic Alterations in Tumours of the Eye

NCT ID: NCT06861647

Last Updated: 2025-07-10

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 70 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-03-25
• Study Completion Date: 2025-02-28

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.

Detailed Description

Uveal melanomas are rare cancers that arise from pigment cells (melanocytes) in the eye. Like most rare cancers, limited interest in developing new therapies and a lack of clinical trials contributes towards relatively worse survival rates compared with common cancers. Following treatment of uveal melanoma with either surgical removal of the eye (enucleation) or local radiation (plaque brachytherapy), approximately half of all patients will develop metastases (new tumours). Most patients will die within a few months despite current therapies.

Conjunctival melanomas (cancer of the surface of the eye which lines the inside of the eyelids) are an extremely rare subset of eye cancers which also have poor survival outcomes once metastasised. Modern DNA sequencing technologies enable researchers to identify mutations acquired during the lifetime of an individual (these are known as somatic mutations). Some of these somatic mutations occur in cancer-associated genes, and increase the risk of developing cancer. This study will use sequencing technologies to look to identify mutations associated with cancers of the eye. By sequencing at different stages of the disease we hope to build a timeline of the order of mutations that occur during eye cancer development. The investigators will also generate cell line models to try and understand how these cancers develop, spread (metastasise) and respond to treatments. The investigators will also look at which somatic mutations are detectable in blood. Blood samples will be collected regularly from participants and circulating tumour DNA, (ctDNA, fragments of DNA released by tumours into the bloodstream) will be sequenced. The investigators will determine whether the mutations present in ctDNA can be used as an indicator of disease progression.

This study will provide much needed insight into a rare and understudied cancer type, with the aim of improving the survival of patients by identifying key mutations to develop novel therapies against.

Conditions

Somatic Mutation; Ocular Melanoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

A (Primary uveal melanoma)

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

sample collection

Intervention Type: OTHER

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

Discussing study/seeking consent

Intervention Type: 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.

Completion of Study Questionnaire

Intervention Type: OTHER

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

Blood Sample

Intervention Type: OTHER

To take place in an outpatient clinic.

B1 (Metastatic uveal melanoma)

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

sample collection

Intervention Type: OTHER

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

Discussing study/seeking consent

Intervention Type: 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.

Completion of Study Questionnaire

Intervention Type: OTHER

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

Blood Sample

Intervention Type: OTHER

To take place in an outpatient clinic.

B2 (Metastatic uveal melanoma, precollected only)

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

No interventions assigned to this group

C (Conjunctival melanoma)

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

No interventions assigned to this group

Interventions

sample collection

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

Intervention Type: OTHER

Discussing study/seeking consent

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.

Intervention Type: OTHER

Completion of Study Questionnaire

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

Intervention Type: OTHER

Blood Sample

To take place in an outpatient clinic.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• Patients < 18 years of age

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Moorfields Eye Hospital NHS Foundation Trust

OTHER

Sponsor Role: collaborator

St. Bartholomew's Hospital

OTHER

Sponsor Role: collaborator

The Wellcome Sanger Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Pui Ying Chan

Role: PRINCIPAL_INVESTIGATOR

Wellcome Sanger Institute

Locations

Wellcome Sanger Institute

Cambridge, , United Kingdom

Countries

United Kingdom

Other Identifiers

242945

Identifier Type: -

Identifier Source: org_study_id