Identifying new tumour markers in oesophageal (gullet) and gastroesophageal (stomach/gullet) cancers
| ISRCTN | ISRCTN11063656 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11063656 |
| IRAS number | 309452 |
| Secondary identifying numbers | 2-014-22, IRAS 309452 |
- Submission date
- 12/08/2022
- Registration date
- 19/08/2022
- Last edited
- 28/03/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English Summary
Background and study aims
People with oesophageal (gullet) and gastroesophageal (stomach/gullet) cancers receive treatments such as, chemotherapy, radiotherapy and surgery, but often they are not effective in curing the cancer. Scientists and doctors are working together to make develop new immunotherapy treatments, immunotherapy helps the immune system fight cancer. There are some immunotherapy treatments for oesophageal and gastroesophageal cancers, but they only work in a small number of people.
There are markers in the cancer cells which can sometimes tell which immunotherapy will work best for a person, called neoantigens. To be able to develop more immunotherapy treatments we first have to find out which neoantigens are in oesophageal and gastroesophageal cancers.
This study will collect cancer tissue samples from people with oesophageal and gastroesophageal cancer. Scientists at Platinum Informatics Ltd will look at the cancer tissue to identify neoantigens.
Who can participate?
• 18 years of age or older
• Willing and able to provide written informed consent
• Histologically confirmed oesophageal or gastroesophageal junctional adenocarcinoma.
What does the study involve?
Participants will be asked to provide tissue biopsy samples of their gullet or gullet/stomach cancer tumours. These samples will be taken when participants are already having procedures carried out for their medical care for their cancer. A small number of participants may be asked if they agree to having an endoscopy specifically to collect biopsy samples for the research study if they are not due to have a medical care procedure. Participants will also give a blood sample when their tissue biopsy sample is collected and 18 weeks later. Participants will be followed up for 18 weeks where details of how their condition progresses will be collected. Participants may also have optional biopsy samples taken on 3 more occasions and optional blood samples on 2 more occasions during the 18 week follow-up period. These will be taken if a participant is having a medical care procedure which would allow this.
What are the possible benefits and risks of participating?
The trial may not immediately benefit the participant, but if the the trial may identify new neoantigens which may lead to targeting of treatments for this group of participants.
Risks:
The tissue biopsy samples will be collected wherever possible when the participants are undergoing biopsy
procedures as part of their routine care. If that is not possible, then the biopsies will be carried out for the study
purpose only. Collecting these tissue samples is considered safe, but the possible risks include:
- Bleeding at the time the samples are removed.
- Infection at the site where the samples are removed.
- Pain at the time the samples are removed.
These complications happen 1 in 1000 endoscopic biopsies and are usually minor and short-lived (discomfort or
minor bleeding at biopsy sites).
Where is the study run from?
University of Dundee (UK)
When is the study starting and how long is it expected to run for?
December 2021 to November 2023
Who is funding the study?
Platinum Informatics Ltd (UK)
Who is the main contact?
Russell Petty, r.petty@dundee.ac.uk
Contact information
Scientific, Principal Investigator
TASC
Level 3 Residency block
Ninewells Hospital
Dundee
DD1 9SY
United Kingdom
 ORCID ID |
0000-0003-2055-4572 |
|---|---|
| Phone | +44 1382 383423 |
| r.petty@dundee.ac.uk |
Public
Tayside Clinical Trials Unit
TASC
Level 3, Residency Block
Ninewells Hospital
Dundee
DD1 9SY
United Kingdom
| Phone | +44 1382 383097 |
|---|---|
| m.band@dundee.ac.uk |
Study information
| Study design | Observational study with specimen collection |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cross sectional study |
| Study setting(s) | Hospital |
| Study type | Screening |
| Participant information sheet | 42225 PROTEAN Patient Information Sheet V1 17May22.pdf |
| Scientific title | Proteomic Profiling of Oesophageal Adenocarcinoma Neoantigens |
| Study acronym | PROTEAN |
| Study hypothesis | To characterise neoantigen profiles of oesophageal or gastroesophageal junction adenocarcinomas |
| Ethics approval(s) | Approved 24/08/2022, Wales REC 6 (Health and Care Research Wales Support and Delivery Centre, Castlebridge 4, 15-19 Cowbridge Road East, Cardiff, CF11 9AB, UK: +44 2920 230457; Wales.REC6@wales.nhs.uk), ref: 22/WA/0223 |
| Condition | Oesophageal cancer |
| Intervention | Medical history • To confirm eligibility • Location of primary tumour • Histological and molecular diagnosis details – Human epidermal growth factor receptor 2 (HER2), PD-L1 testing • Tumour stage according to AJCC/UICC version 8 for cancers of the oesophagus and stomach • Stage and location of metastases • Progression assessment – RECIST Criteria 1.1 • Medical co-morbidities • Smoking history Demographics • Age, gender, body mass index Concomitant medication • Details of any scheduled or prior cancer treatment Biopsy • A fresh tumour biopsy will be collected: o Prior to the commencement of any subsequent scheduled anticancer treatments*; OR o After the completion of the latest line of anticancer treatment*; OR o During follow up when a participant is not receiving or is between scheduled anti-cancer treatments*. *Anti-cancer treatments excluding surgery • The biopsy may be obtained from any site of tumour, primary or metastatic as considered the most appropriate and feasible at the time of the procedure. • Biopsies from more than one tumour site may be obtained at the same time point and procedure, but this is not mandatory, only biopsy of a single tumour site is required for study participation. • Up to 10 biopsies, approximately 2mm each, will be taken at each timepoint and if tumour biopsy is being undertaken by endoscopy 2 biopsies approximately 2mm each of adjacent normal oesophageal or gastric mucosa. • As far as possible, tumour biopsies for the study will be obtained during routine clinical care procedures e.g. endoscopy, surgery, stenting. However, where this is not possible, consent will be requested for study specific procedures for biopsy to obtain tumour material. • Participants may provide additional consent for further biopsies during further routine clinical care procedures to be taken as an optional part of the study. Research bloods • A maximum of 20ml of blood will be collected at each visit. • Sites which have the facilities to carry out peripheral blood mononuclear cell preparations (PBMC) analysis will process and complete analysis on site. These samples will be processed at sites for PBMCs. • Details of sample collection, processing, storage and transfer will be provided in PROTEAN Clinical Sample Handling Manual. Outcome assessment • Tumour response status according to RECIST v1.1 • Overall Survival • Adverse events (AE) The total duration of observation and follow up is 18 weeks. |
| Intervention type | Other |
| Primary outcome measure | Neoantigen profiles for individual patients with oesophageal or gastroesophageal junction adenocarcinomas measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) of tumour biopsies taken at Day 1 and a maximum of 3 further optional research biopsy samples may be collected between day 1 and week 18, timings will vary for participants for these biopsies to fit in with their standard care procedures. |
| Secondary outcome measures | 1. Proportion of patients in which neoantigen profiles are successfully generated measured as percent of patients in the study for whom neoantigen profiles are obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) of their tumour biopsies taken at Day 1 and a maximum of 3 further optional research biopsy samples may be collected between day 1 and week 18, timings will vary for participants for these biopsies to fit in with their standard care procedures. 2. Characterise pre-existing T cell responses to identified neoantigens measured by ex vivo IFN Gamma ELISPOT assays on peripheral blood mononuclear cells isolated from patients stimulated with synthesized neoepitope peptides identified from patient's tumour biopsies 3. Correlate objective response rate, disease control rate, progression free survival and overall survival with neoantigen profiles measured by analysis of participants grouped by any identified common features of neoantigen profiles of tumours 4. Genomic and transcriptomic analysis and neoantigen validation measured by Whole genome sequencing and RNA sequencing of tumour biopsies and compared to neoantigen profiles of individual patients with oesophageal or gastroesophageal junction adenocarcinomas measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) of tumour biopsies |
| Overall study start date | 01/12/2021 |
| Overall study end date | 11/10/2023 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 75 |
| Total final enrolment | 86 |
| Participant inclusion criteria | 1. 18 years of age or older 2. Willing and able to provide written informed consent 3. Histologically confirmed oesophageal or gastroesophageal junctional adenocarcinoma. 4. Able to provide a tumour biopsy sample as per protocol requirements |
| Participant exclusion criteria | 1. Concurrent systemic anti-cancer treatment and/or radiotherapy (participants undergoing cancer surgery are eligible.) 2. Any significant medical condition that in the opinion of the Principal Investigator (PI) would impair the ability of the participant to complete the requirements of the protocol |
| Recruitment start date | 01/09/2022 |
| Recruitment end date | 31/03/2023 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Dundee
DD1 9SY
United Kingdom
Glasgow
G4 0SF
United Kingdom
Tremona Road
Southampton
SO16 6YD
United Kingdom
Great George Street
Leeds
LS1 3EX
United Kingdom
Sponsor information
University/education
TASC
Level 3
Residency Block
Ninewells Hospital
George Pirie Way
Dundee
DD1 9SY
Scotland
United Kingdom
| Phone | +44 1382383297 |
|---|---|
| TASCgovernance@dundee.ac.uk | |
| Website | https://www.dundee.ac.uk/tasc/ |
"ROR" |
https://ror.org/03h2bxq36 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 30/06/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | General laboratory data methods and results will be documented in laboratory notebooks and then analysed and written up for publication for dissemination to the scientific community. All electronic data will be stored on password-protected computers in secure staff access -controlled offices at investigator sites. All data and laboratory notebooks will be retained for at least ten years, in accordance with general RCUK guidelines. The report will be made available to the funder. The report can be used for publication and presentation at scientific meetings. Study investigators have the right to publish study results orally or in writing. The criteria for authorship will follow the criteria of the International Committee of Medical Journals. Publications will be reviewed according to the agreed contractual terms but will not restrict the general rights outlined above for the Investigators to publish the results of the study. |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 1 | 17/05/2022 | 19/08/2022 | No | Yes |
| Protocol file | version 1 | 17/05/2022 | 19/08/2022 | No | No |
| Participant information sheet | version 2 | 19/08/2022 | 05/09/2022 | No | Yes |
| HRA research summary | 28/06/2023 | No | No | ||
| Other unpublished results | 29/01/2025 | No | No |
Additional files
Editorial Notes
28/03/2025: Contact details updated.
29/01/2025: Unpublished results summary added.
04/06/2024: The following changes were made to the study record:
1. The study participating centres were updated to remove Velindre Hospital, Addenbrookes, Queen Margaret Hospital, Leicestershire Partnership NHS Trust (university Hospitals), Queen's University of Belfast, Oxford Experimental Cancer Medicine Centre.
2. The intention to publish date was changed from 30/06/2024 to 30/06/2025.
06/11/2023: The following changes were made to the trial record:
1. The overall end date was changed from 30/11/2023 to 11/10/2023.
2. The intention to publish date
3. The total final enrolment was added.
04/01/2023: The recruitment end date was changed from 31/01/2023 to 31/03/2023.
05/09/2022: The following changes have been made:
1. The ethics approval has been added.
2. An updated participant information sheet has been uploaded.
19/08/2022: Trial's existence confirmed by Wales REC 6
