Somatic MutationiSITENCT06861647
iSITE: Investigation of Somatic Alterations in Tumours of the Eye
An observational study of Somatic Mutation and Ocular Melanoma, run by The Wellcome Sanger Institute at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Somatic Mutation, Ocular Melanoma
- What is being tested?
- sample collection, Discussing study/seeking consent and Completion of Study Questionnaire
- How many people
- 58 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 25 Mar 2019to 28 Feb 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- Patients < 18 years of age
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- sample collection, Discussing study/seeking consent, Completion of Study Questionnaire, Blood Sample
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sample collectionOther
sample collection of surplus samples not needed for diagnostic or pathological requirements
Discussing study/seeking consentOther
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 QuestionnaireOther
Patient will complete in own time. To take place in a routine outpatient clinic appointment
Blood SampleOther
To take place in an outpatient clinic.
| Study group | Role | What they receive |
|---|---|---|
| A (Primary uveal melanoma) | Prospective collection, primary uveal melanoma. If patients have previously collected samples, consent will be requested to also obtain these samples. Receives: 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. Receives: 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 , |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Cohorts A and B1: Uveal melanoma only.
This study will include longitudinal blood sampling for the detection of mutations in ctDNA. If these mutations are found to be a real-time reflection of the mutations present within the tumour, this would be a valuable minimally-invasive approach to studying tumour evolution and monitoring disease.
Measured: 6.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2025
- Study start25 Mar 2019
- Primary completion7 Feb 2022
- Study completion28 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Somatic MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Wellcome Sanger Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Moorfields Eye Hospital NHS Foundation Trust, St. Bartholomew's Hospital
- Responsible party
- Sponsor
- Investigators
- Pui Ying Chan, Principal investigator, Wellcome Sanger Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06861647
- Sponsor's protocol ID
- 242945
- Acronym
- iSITE
- Status last verified
- Jul 2025
- First submitted
- 7 Feb 2025
- Last updated
- 1 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- iSITE: Investigation of Somatic Alterations in Tumours of the Eye
- ClinicalTrials.gov ID
- NCT06861647
- Acronym / sponsor ID
- iSITE / 242945
- Conditions
- Somatic Mutation, Ocular Melanoma
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- The Wellcome Sanger InstituteUniversity, hospital or other
- Collaborators
- Moorfields Eye Hospital NHS Foundation Trust, St. Bartholomew's Hospital
- Study start
- 25 Mar 2019 (actual)
- Primary completion
- 7 Feb 2022 (actual)
- Study completion
- 28 Feb 2025 (actual)
- First posted
- 6 Mar 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Other
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| A (Primary uveal melanoma) | – | Other: sample collection, Other: Discussing study/seeking consent, Other: Completion of Study Questionnaire, Other: Blood SampleProspective collection, primary uveal melanoma. If patients have previously collected samples, consent will be requested to also obtain these samples. |
| B1 (Metastatic uveal melanoma) | – | Other: sample collection, Other: Discussing study/seeking consent, Other: Completion of Study Questionnaire, Other: Blood SampleProspective collection, metastatic uveal melanoma. If patients have previously collected samples, consent will be requested to also obtain these samples. |
| 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 , |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (1 listed)
- Patients < 18 years of age
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sample collectionsample collection of surplus samples not needed for diagnostic or pathological requirements | Other | A (Primary uveal melanoma), B1 (Metastatic uveal melanoma) |
| Discussing study/seeking consentAn 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. | Other | A (Primary uveal melanoma), B1 (Metastatic uveal melanoma) |
| Completion of Study QuestionnairePatient will complete in own time. To take place in a routine outpatient clinic appointment | Other | A (Primary uveal melanoma), B1 (Metastatic uveal melanoma) |
| Blood SampleTo take place in an outpatient clinic. | Other | A (Primary uveal melanoma), B1 (Metastatic uveal melanoma) |
Primary outcome
Measuring what somatic mutations are acquired during development and metastases in uveal melanomas and conjunctival melanomas.
Time frame: 6.5 years
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.
Measure whether tumour intratumoural heterogeneity (the mixture of different tumour cell types within one tumour) is associated with a poor clinical outcome.
Time frame: 6.5 years
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.
Measuring the burden and prevalence of somatic mutations in normal and cancer samples of tumours of the eye
Time frame: 6.5 years
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.
1 secondary outcome
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.
Time frame: 6.5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pui Ying Chan principal investigator
Wellcome Sanger Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Somatic Mutation and Ocular Melanoma, run by The Wellcome Sanger Institute at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measuring what somatic mutations are acquired during development and metastases in uveal melanomas and conjunctival melanomas. (time frame: 6.5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2026; AzTrials last refreshed its copy on 8 Nov 2026.