iSITE: Investigation of Somatic Alterations in Tumours of the Eye
Conditions: Somatic Mutation, Ocular Melanoma
Sponsor: The Wellcome Sanger Institute

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
 
 
 
 
 
 
Investigation of Somatic alterations in Tumours of the Eye 
 
 
STUDY PROTOCOL 
IRAS Number: 242945 
 
 
 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 1 of 11 
KEY STUDY CONTACTS  
Chief Investigator 
 
Pui Ying Chan  (email:  
Wellcome Sanger Institute 
Hinxton CB10 1SA 
 
 
 
 
Sponsor  
 
 
Genome Research Limited 
Wellcome Genome Campus  
Hinxton CB10 1SA 
Sponsor representative:  
Dr Martin Dougherty  
(email: md21@sanger.ac.uk) 
Sponsor contact: 
 
Dr Joanne Doleman  
(email: researchgovernance@sanger.ac.uk) 
Phone:  
 
 
01223 495399  
 
Funders  
 
 
The Wellcome Trust  
The Wellcome Sanger Institute  
 
ROLE OF STUDY SPONSOR AND FUNDER 
The roles and responsibilities of the sponsor and funder do not extend to the study design or conduct. Data analysis 
and interpretation will be carried at the Wellcome Sanger Institute (SANGER). The dissemination of results will be 
in accordance with the SANGER Data Sharing Policy and the SANGER Publication Policy. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 2 of 11 
 
 
STUDY SUMMARY 
Study Title 
Investigation of Somatic alterations in Tumours of the Eye 
Short Title 
iSITE  
Study Design 
An observational cohort study of patients with ocular melanoma. 
Study Participants 
Patients > 18 years of age diagnosed with ocular melanoma.   
Planned Sample Size  
Target accrual: 
• 
Cohort A: 104 uveal melanoma patients  
• 
Cohort B1: 16 uveal melanoma patients  
• 
Cohort B2: 50 uveal melanoma patients  
• 
Cohort C: 10 conjunctival melanoma patients  
Follow Up Duration  
Up to 3 years 
Planned Study Period 
July 2018 – December 2024 
Research Objectives 
 
Define the order of somatic mutations leading to cancer development, 
metastases and resistance to treatment.  
 
Explore how somatic mutations compare across different regions within the 
same tumour. 
 
Determine whether mutations detected in circulating tumour DNA reflect 
the mutational landscape of tumours from the same patient. 
 
GLOSSARY 
Buffy coat 
 
 
Layer of concentrated white blood cells and platelets in centrifuged blood.  
Enucleation 
 
 
Surgical removal of the eye. 
FFPE 
 
 
Formalin-fixed paraffin-embedded.  
Germline 
 
 
Inherited genetic material from eggs or sperm that are passed on to offspring. 
Malignant 
 
 
Term used to describe cells which have become cancerous. 
Metastasis 
 
 
Spread of the original cancer to a distant site. 
Uveal melanoma 
 
 
A disease where cancer cells form in the uveal tract of the eye.   
Local recurrence 
 
 
Re-growth of the original eye tumour in the eye, following treatment. 
Observational cohort study  
Following a group of individuals over time to determine certain outcomes, 
where no attempt is made to affect the outcome.  
Ocular melanoma 
 
 
Collective term for cancers of the eye, including uveal melanoma and 
conjunctival melanoma. 
Plaque brachytherapy 
 
Small metal disc placed on the surface of the eyeball, emitting radiation 
over a number of days before being removed from the eyeball. 
Somatic mutation 
 
 
Non-inherited genetic alteration acquired by a cell.  
Subclone 
 
 
Population of cells with mutations different from the major population of cells 
in the tumour. 
Tumour 
 
 
Abnormal growth of tissue. 
Vitreous fluid  
 
 
Fluid that fills the space between the lens and the back of the eye. 
 
 
 
 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 3 of 11 
 
 
TITLE 
Investigation of somatic alterations in tumours of the eye (iSITE). 
 
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. We can use 
this information to understand how these cancers develop, spread (metastasise) and respond to treatment. 
Furthermore, we 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.  
 
RATIONALE OF THE STUDY 
Uveal Melanoma  
Uveal melanomas (cancer of the eye involving the iris, ciliary body, or choroid - collectively referred to as the uvea) 
are rare cancers that arise from pigments cells (melanocytes) located in the eye. Like most rare cancers, there is 
limited interest in developing new therapies and a lack of clinical trials. This strongly contributes towards the 
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 the 
patients will go on to develop metastases. Most patients will die within a few months despite current therapies1. 
Many of the treatments currently available to patients with metastatic uveal melanoma were initially developed for 
skin cancer (cutaneous melanoma), which arise from pigment cells of the skin. Patients with uveal melanoma were 
underrepresented and often excluded from the very clinical trials that led to the approval of the drugs they are now 
treated with. Importantly, despite both cancers arising from melanocytes, uveal melanoma and cutaneous 
melanoma are completely distinct in their mutational profile, and indeed their clinical behaviour. It is therefore not 
surprising that the treatments currently being used are not effective in uveal melanoma.  
 
Conjunctival Melanoma  
Conjunctival melanomas (cancer of the surface of the eye which lines the inside of the eyelids) are an extremely 
rare subset of ocular melanomas. They share more similarities to cutaneous melanoma in their clinical behaviour. 
Whilst there are similarities in the mutational profiles of conjunctival and cutaneous melanoma, the order of 
mutational changes acquired during development, growth and recurrence of conjunctival melanoma remain poorly 
understood. As such, few advances have been made in the treatments offered to the metastatic patient population, 
resulting in poor survival outcomes.  
 
This study will address the following unique questions: 
(1) What somatic mutations are acquired during development and metastases?  
(Cohorts A, B1, B2 and C: Uveal melanoma and conjunctival melanoma) 
 
Different mutations can lead to cancer development in the eye, the spread of cancer to other parts of the 
body and resistance to treatment. Tracking the mutational changes of a tumour in the same patient over 
time during each of these stages will allow us 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. To date only one small study of paired primary and metastatic uveal 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 4 of 11 
melanoma samples has been performed, revealing a group of 135 mutations across 5 paired samples2. 
The mutational profiles of paired primary and metastatic conjunctival melanomas have not been 
comprehensively studied. 
 
(2) Is intratumoural heterogeneity associated with poor clinical outcome?  
(Cohorts A, B1, B2 and C: Uveal melanoma and conjunctival melanoma) 
 
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.  
 
(3) Do mutations detected in ctDNA reflect the somatic mutations found within the tumour? 
(Cohorts A and B1: Uveal melanoma only)  
 
ctDNA carry tumour-specific mutations which allow identification and differentiation from non-tumour DNA. 
ctDNA is detectable in many different cancer types including uveal melanoma, and ctDNA levels have 
been shown to correlate with tumour burden and survival outcomes3. 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.   
 
RESEARCH QUESTIONS 
(1) What is the order of somatic mutations leading to cancer development, metastases and resistance to 
treatment in ocular melanomas?  
 
(2) How do somatic mutations compare across different regions within the same ocular tumour? 
 
(3) Do the mutations detected in circulating tumour DNA reflect the mutational landscape of uveal tumours? 
 
EXPERIMENTAL DESIGN AND METHODS 
Typical diagnostic and treatment schedules for primary and metastatic uveal melanoma are summarised below.  
 
  Primary uveal melanoma     
  Moorfields Eye Hospital:                                 Clinical diagnosis 
 
Intraocular biopsy not routinely performed  
(unless specific reason e.g. patient choice, diagnostic uncertainty) 
 
Routine blood sampling 
 
Plaque brachytherapy (excess tumour tissue and vitreous fluid not typically available following surgery) 
OR 
Enucleation (excess tumour tissue and vitreous fluid available following surgery) 
 
  St Bartholomew’s Hospital:                                           
First metastatic surveillance appointment  
(routine blood sampling for all patients) 
 
Lifelong surveillance for metastatic disease: 6 monthly radiological scans of the liver 
(Blood sampling is not routinely performed as part of metastatic surveillance) 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 5 of 11 
 
 
 
  Metastatic uveal melanoma     
  St Bartholomew’s Hospital:                       Radiological diagnosis 
 
Biopsy of metastatic disease is routinely performed for histological confirmation  
 
Routine blood sampling 
 
Surgery for minority of patients who have low burden of metastatic disease (excess tumour tissue available) 
OR 
Systemic therapy for majority of patients (routine blood sampling during treatment) 
 
Surveillance post-treatment (routine blood sampling) 
 
Metastatic biopsies may be performed e.g. upon disease progression (not routine) 
 
  Typical systemic therapy options: 
  Ipilimumab 
 
  Pembrolizumab 
 
  Ipilimumab with nivolumab 
 
3 weekly ipilimumab for a total of 4 treatments. 
 
3 weekly pembrolizumab until intolerance or disease progression.  
 
3 weekly combination ipilimumab and nivolumab for 4 treatments,                 
followed by 2 weekly nivolumab until intolerance or disease progression. 
 
 
 
 
This study will be divided into several cohorts: Samples will be prospectively collected from patients with both 
primary uveal melanoma (cohort A) and metastatic uveal melanoma patients (cohort B1). If the patients in cohorts 
A and B1 have stored samples which have been previously collected, consent will be requested from these patients 
to obtain these samples.  
 
Previously collected and stored tissue samples will be retrospectively collected from patients with metastatic uveal 
melanoma patients (cohort B2) and primary and/or metastatic conjunctival melanoma (cohort C). There will be no 
prospective sampling from cohorts B2 and C. 
 
Pre-collected blood samples will be purchased from commercial providers to enable us to test our experiments 
with less precious samples before we utilise the samples collected as part of this study. 
 
 
 
 
 
Prospective sample collection 
Retrospective sample collection 
Primary uveal melanoma 
Cohort A 
 
 
Metastatic uveal melanoma 
Cohort B1 
 
 
Cohort B2 
 
 
Conjunctival melanoma 
Cohort C 
 
 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 6 of 11 
 
 
 
 
Eligibility criteria 
Patients will be eligible for the study, as defined below.  
Inclusion criteria  
 
Patients ≥ 18 years of age (no upper age limit). 
 
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. 
 
Recruitment and Consent 
Cohorts A and B1 (prospective and retrospective sampling) 
 
For cohorts A and B1, a member of the patient’s existing 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. If so they will be introduced to the study and offered a participant 
information sheet (PIS) during an outpatient consultation.  
 
If a patient is interested in the study and wishes to find out more and/or participate in the study, a further 
appointment will be made in a specialist clinic or dedicated study-specific clinic, in addition to the normal routine 
care appointments, for recruitment onto this study. At this visit, a designated and trained 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 the opportunity 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.  
 
Written informed consent will be obtained prior to the participant undergoing any activities that are specifically for 
the purposes of the study. This will include the collection of patient clinical information, which will be linked 
anonymised. Upon entry into the study participants will be asked to complete a questionnaire on personal 
characteristics and family history of related cancers. All patients recruited onto the study will be suitable for 
treatment in accordance with NICE guidelines and standard of care. Consent will also be received from participants 
for use of their previously obtained blood and/or tissue samples, which may be stored within the local pathology 
diagnostic archive. Local sites are responsible for: 
 
 
Assessing patient capacity to give informed consent;  
 
Ensuring patients receive latest REC approved version of the participant information sheet and consent 
form; 
 
Receiving and storing written informed consent and providing the participants with a copy of this consent. 
 
Cohorts B2 and C (retrospective sampling only) 
 
For cohorts B2 and C, a member of the patient’s existing clinical care team, a research nurse or member of the 
Clinical Research Network (CRN) will have access to patient records to retrospectively identify patients and 
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.  
 
For the majority of samples in these two cohorts consent for the use of the samples in research would have been 
received at the time of sample collection using the hospitals standard consent from. For some of the samples in 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 7 of 11 
cohort B2 and cohort C consent for use of the samples for research may not have obtained when these samples 
were collected. Given the poor survival outcomes in these populations of patients, it is anticipated that most 
patients within these cohorts will be deceased by the time of study set up, as such it would not be possible to re-
consent the patients for inclusion in this study. However, given that the samples were collected from the living at 
the time of collection, they will be anonymous to the Sanger research team and they are a recognised rare tumour 
type, we are seeking REC approval for the use of these samples in this study. 
 
Sample Collection 
 
 
Tissue collection (all cohorts) 
Primary and locally recurrent tumour and healthy samples will be collected from the UCL Institute of Ophthalmology 
and /orMoorfields Biobank. Metastatic tumour samples will be collected from St Bartholomew’s Hospital, Cancer 
Tissue Bank @ Barts Health. All tissue samples will be taken from surplus material following biopsies or surgery. 
Specimens used in the study will be surplus to diagnostic and pathological requirements, and comprise FFPE 
blocks or sections. Where possible, fresh tissue will be obtained at the time of surgery for sequencing, and in a 
subset of patients to generate cell lines. If samples have been collected from ocular melanoma patients as part of 
other REC approved studies, we will receive consent from the patient to use any available surplus samples in the 
iSITE study. 
 
Blood samples will be purchased from commercial providers active in the UK whom provide access to samples 
collected with fully informed consent for use in research. 
 
Typical tissue storage sites 
Eye Tissue 
Metastatic Tissue 
Diagnostic archive 
UCL Institute of Ophthalmology 
St Bartholomew’s Hospital 
Research tissue bank 
Moorfields Biobank 
Cancer Tissue Bank @ Barts Health 
 
Vitreous Fluid collection (cohort A) 
Vitreous fluid is not required for diagnostic purposes and is removed with the eye during enucleation. In patients 
undergoing enucleation who have consented for their primary tumours to be used for research, up to 2mls of vitreous 
fluid will be aspirated in theatres by the operating team, immediately after the eye has been enucleated. This will take 
place in the operating theatres at Moorfields Eye Hospital. 
 
 
Whole blood collection (cohorts A and B1) 
Blood sampling for cohort A will initially take place at Moorfields Eye Hospital (2 time points) where the primary 
treatment is being carried out. The remaining blood samples for cohort A will be collected at St Bartholomew’s 
Hospital, where patients are routinely commenced on surveillance. Blood sampling for cohort B1 will take place in 
St Bartholomew’s Hospital, where patients are treated for metastatic disease. As much as possible, additional 
research blood sampling all study participants will coincide with their routine treatment visits. 
 
30mls of whole blood will be collected from patients at all time points. Whole blood samples taken at baseline and 
at first recurrence will be processed for buffy coat and plasma analysis. At all other time points, 30mls of whole 
blood will be collected and processed for plasma analysis. Samples will be stored at -80°C locally prior to being 
transferred to SANGER. The maximum total blood draw for each patient per annum is anticipated to be 150mls 
for cohort A (5 time points, 30mls per time point) and 540mls for cohort B1 (18 time points for the majority of 
patients, 30mls per time point). 
 
 
Retrospective sample collection (all cohorts) 
 
In addition, local site research teams will request surplus healthy and diseased tissue, vitreous fluid and blood 
samples which have been previously collected from UCL Institute of Ophthalmology, St Bartholomew’s Hospital, 
Moorfields biobank, Cancer Tissue Bank @ Barts Health and local hospitals (including samples that have been 
processed for extraction of nucleic acids) and stored in:  

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 8 of 11 
 
 
(a) Local Pathology Diagnostic Archives by liaising with their local pathology department;     
(b) Research Tissue Banks by liaising with their local Research Tissue Bank Manager. 
 
 
 
 
 
 
 
 
 
Sample Processing  
 
Multi-region sampling will be performed using techniques such as microscopy-guided dissection. DNA and/or RNA 
will be extracted from these and other patient-derived samples including blood. Libraries will be prepared and 
sequenced on the Illumina HiSeq 4000 or other platforms. Non-tumour regions within tissue specimens and buffy 
coats from blood samples will undergo similar methods for germline analysis. Sequencing may be whole genome, 
whole exome or to targeted sets of cancer genes.  
 
Primary sequence data will be entered into the SANGER variant calling pipelines, to identify somatic base changes 
and structural variants. This information will be correlated with linked anonymised patient clinical data (e.g. 
pathology reports, scan reports) in all cohorts, to determine their association with clinical outcomes. 
 
Where feasible, fresh tumour samples will be collected from patients during standard procedures such as biopsy 
or enucleation, for (i) sequencing to allow for more accurate identification of mutations and (ii) to develop uveal 
melanoma cancer cell models such as cell lines and organoids. These will be used to study disease biology in 
vitro and predict response and resistance to therapies. Consent will be received from patients to deposit any 
anonymised samples and cancer cell line models, remaining at the end of the study, into tissue and/or cell banks 
for future ethically approved research. 
 
 
Statistical Plan 
 
The target accrual for each cohort is listed below:  
• 
Cohort A: 104 uveal melanoma patients  
• 
Cohort B1: 16 uveal melanoma patients  
• 
Cohort B2: 50 uveal melanoma patients  
• 
Cohort C: 10 conjunctival melanoma patients  
 
 
Cohorts A and B1 
 
The sample size required for ctDNA analysis is heavily influenced by the sensitivity of the methods used to detect 
ctDNA. This is determined by both the error rate of the methods used (to be established as part of the study) and 
the number of mutations detected (to be established from the number of mutations present in tumour samples). 
Due to the exploratory nature of the analyses, this study will aim for a conservative target accrual of 20% over 2.5 
years (104 patients) for cohort A and 75% accrual over 2.5 years (16 patients) for cohort B1. 
 
 
Cohorts B2 and C 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 9 of 11 
 
The graph on the left represents the 
number of samples required to detect a 
mutation at a given frequency, with 90% 
power 
(i.e. 
a 
cumulative 
binomial 
probability of 90%). It forms the basis of 
the target accrual for cohort B2. In this 
study, with a cohort B2 sample size of 50 
patients, and a frequency of mutation of 
4.5%, we estimate that the power to 
detect at least one patient with a 
mutation is 90%. The maximum accrual 
for cohort C is predicted to be 10 patients 
due to the extremely low incidence of 
metastatic conjunctival melanoma.  
 
 
 
 
 
STUDY FLOW CHART 
Newly diagnosed uveal melanoma patients (cohort A, in green on study flow chart) will be invited to take part in 
the study and offered Version A of the PIS. Patients with metastatic uveal melanoma (cohort B1, in blue on study 
flow chart) will be invited to take part in the study and offered Version B of the PIS. Patients in cohort A who go on 
to develop metastatic disease can be recruited into cohort B1. Metastatic uveal melanoma tissue samples (cohort 
B2,) and conjunctival melanoma tissue samples (cohort C, both B2 and C in purple on study flow chart) will be 
retrospectively identified and collected from diagnostic archives and research tissue banks. Patients will not be 
prospectively recruited into cohort B2 and cohort C.  
 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 2 of 11 
 
 
 
 
 
 
 
 
 
 
 
The timing and type of samples to be collected is outlined below.  
 
COHORT A  
New diagnosis 
uveal melanoma  
Baseline 
At diagnosis /               
prior to treatment 
Treatment 
During surgery  
Surveillance 
3 monthly research 
clinics 
End of study  
3 years after entry 
into study 
Tumour tissue 
Nil  
Fresh tissue               
(if available) 
FFPE blocks  
Nil 
Nil 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 3 of 11 
H&E slides* 
Vitreous fluid 
Nil 
0.5 to 2.0mls                
(if enucleation)  
Nil 
Nil 
Whole blood 
30mls blood 
30mls blood  
 
30mls blood (first 
sample to be taken 
prior to discharge, 
following surgery) 
30mls blood 
Archived 
samples            
(if available) 
Previously collected 
samples (inc. tissue 
& blood) 
Nil 
Nil 
Nil 
 
COHORT B1  
Metastatic uveal 
melanoma 
Metastasis 
Prior to systemic 
treatment  
Systemic treatment 
Prior to each cycle & 
at completion of 
therapy (typical 
treatment schedule 
shown on next page) 
Surveillance 
3 monthly 
research clinics /  
routine clinic 
visits (whichever 
more frequent) 
Progression 
At failure of 
treatment  
End of 
study  
3 years  
after entry 
into study 
Tumour tissue 
Fresh tissue               
(if available) 
FFPE blocks  
H&E slides* 
Nil 
Nil 
Fresh tissue     
(if available) 
FFPE blocks  
H&E slides* 
Nil  
Whole blood 
30mls blood 
30mls blood  
30mls blood  
30mls blood 
30mls blood 
Archived 
samples               
(if available) 
Previously collected 
samples (inc. tissue 
& blood) 
Nil 
Nil 
Nil 
Nil 
 
COHORT B2 
Metastatic uveal melanoma 
& COHORT C  
Conjunctival melanoma          
Primary Tumour  
Taken at time of 
diagnosis 
Local Recurrence 
Recurrence within the 
eye  
Distant Recurrence 
Recurrence outside of the 
eye  
Archived samples (Healthy 
and diseased)               (if 
available) 
FFPE blocks  
H&E slides* 
FFPE blocks  
H&E slides* 
FFPE blocks  
H&E slides* 
*Should FFPE blocks be unavailable, H&E slides will be collected instead.  
 
 
Patient & Public Involvement 
This study is a follow up of a pilot study of 18 patients who were successfully enrolled over a period of 8 months 
between July 2016 and February 2017. Patients and their relatives were consulted during clinic consultations on 
the design and acceptability of the research being carried out. This contributed towards the design of the research 
with respect to decisions regarding volume of blood sampling and frequency of both blood sampling and clinic 
visits. It is not anticipated that participation within the study will be associated with significant risks outside of those 
pertaining to phlebotomy.  
 
 

iSITE Protocol Version 2.0 
IRAS ID 242945 
       Date 17/08/23 
 
Page 4 of 11 
ETHICAL CONSIDERATIONS 
Research Ethics Committee (REC) and other Regulatory Review  
Health Research Authority (HRA) approval and NHS REC approval for the study will be sought. Substantial 
amendments will not be implemented until approval had been received. In accordance with the Human Tissue Act 
2004 (Ethical Approval, Exceptions from Licensing and Supply of Information about Transplants) Regulations 
2006, human tissue held for a REC approved research project can be stored on premises without a HTA licence. 
 
Data Protection and Patient Confidentiality  
No personal identifiable information will be shared with the sponsor organisation or the research team at Sanger. 
As all participant data in this study will not allow for participant identification, both using the data on its own, or in 
combination with other accessible information, it is not classed as personal data, and the GDPR transparency 
requirements do not apply. All investigators and study site staff will comply with the requirements of the Data 
Protection Act 1998 with regards to the collection, storage, processing and disclosure of personal information. To 
maintain patient confidentiality, all participants in the study will be assigned a unique study identifier code. The link 
between the identifiable participant information and the unique study code will be maintained on password 
protected computers at each recruiting study site. The research team at SANGER will not have access to this 
linkage information. Any information or documentation (e.g. pathology reports, scan reports) being transferred 
between participating sites and researchers will labelled only with this unique identification code. Individual patients 
will be referred to only by their unique study identifier, and any other patient identifiers will be removed/redacted.  
 
Human genetics and/or genomics data will be processed in accordance with the SANGER Human Data Security 
Policy. The raw genetic information that is produced will be deposited and stored indefinitely in a central electronic 
data archive such as the European Genome-Phenome Archive (EGA), which is a secure database established by 
the European Bioinformatics Institute, Hinxton, Cambridge, UK, for the sharing of data with the research 
community. Access to the anonymised information stored in this archive will only be accepted via applications from 
appropriately qualified researchers who sign a legally-binding Data Access Agreement in which they commit to: 
 
• 
use the data only for research purposes;  
• 
protect the data confidentiality;  
• 
provide appropriate data security;  
• 
not attempt to identify individual participants from whom data were obtained; 
• 
not redistribute the data or any subset or derivative that could be used to identify the research participant.  
 
 
REFERENCES 
[1] Nathan P., Cohen V., Coupland S., et al. (2015) 'Uveal melanoma UK national guidelines'. European journal of 
cancer, 51(16): 2404-2412. 
[2] McCarthy, C., Kalirai, H., Lake, S. L., et al. (2015) ‘Insights into Genetic Alterations of Liver Metastases from 
Uveal Melanoma’, Pigment Cell & Melanoma Research, 29: 60-67.  
[3] Bidard, F.-C., Madic, J., Mariani, P., et al. (2014) ‘Detection rate and prognostic value of circulating tumor cells 
and circulating tumor DNA in metastatic uveal melanoma’, International Journal of Cancer, 134(5): 1207–1213.