Clinical trial NCT06861647: ISITE: Investigation of Somatic Alterations in Tumours of the Eye
Official title: ISITE: Investigation of Somatic Alterations in Tumours of the Eye
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Somatic Mutation
Ocular Melanoma
Lead sponsor: The Wellcome Sanger Institute
Sponsor class: OTHER
Collaborators: name: Moorfields Eye Hospital NHS Foundation Trust
name: St. Bartholomew's Hospital
First posted: 2025-03-06
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: OTHER
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.

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.

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

Primary outcomes:
measure: Measuring what somatic mutations are acquired during development and metastases in uveal melanomas and conjunctival melanomas.
timeFrame: 6.5 years
measure: Measure whether tumour intratumoural heterogeneity (the mixture of different tumour cell types within one tumour) is associated with a poor clinical outcome.
timeFrame: 6.5 years
measure: Measuring the burden and prevalence of somatic mutations in normal and cancer samples of tumours of the eye
timeFrame: 6.5 years
Secondary outcomes:
measure: 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.
timeFrame: 6.5 years
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Wellcome Sanger Institute
Study officials:
affiliation: Wellcome Sanger Institute
name: Pui Ying Chan
role: PRINCIPAL_INVESTIGATOR
References: