A clinical trial to investigate if proton beam therapy with chemotherapy given before surgery for patients with oesophageal cancer that has spread to the surrounding tissues, significantly reduces the severe side effects to the heart and lungs and allows immunotherapy to be started sooner after surgery when compared with standard radiotherapy and chemotherapy before surgery, and whether this delivers value to the NHS and patients
| ISRCTN | ISRCTN50098578 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN50098578 |
| IRAS number | 329646 |
| Secondary identifying numbers | CPMS 58475, IRAS 329646 |
- Submission date
- 27/12/2023
- Registration date
- 15/02/2024
- Last edited
- 08/11/2024
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
Although the optimal treatment strategy in oesophageal (food pipe) cancer has been the subject of research for several decades, overall outcomes are very poor, with a 5-year survival of 15%. In the UK there are 9100 new cases of oesophago-gastric cancer diagnosed and approximately 7925 deaths every year (Cancer Research UK Oct 2019). Oesophageal cancer is a strategic priority for CRUK and a serious health problem world-wide. Pre-surgery treatment consists of chemotherapy or chemoradiation, but the optimal treatment is unknown. Over 60% of patients experience severe side-effects from their treatment and this impacts their outcomes. Proton beam therapy is a new radiotherapy treatment; there are currently only 2 centres in England with Proton beam therapy machines. Proton beam therapy may help to reduce side-effects and is an important avenue of research. This trial has been funded by CRUK.
This study aims to investigate if Proton beam therapy and chemotherapy given before surgery for oesophageal cancer significantly reduces the risk of severe toxicity and prevents delay of post-operative immunotherapy when compared with standard photon radiotherapy.
Who can participate?
Patients over 16 years old with resectable oesophageal cancer.
What does the study involve?
Patients will be randomised 1:1 into the experimental arm (Proton beam therapy, chemotherapy + surgery) and control arm (photon radiotherapy, chemotherapy + surgery). Patients suitable for immunotherapy will then receive up to 12 months of treatment as per standard of care. This UK trial will recruit patients from 15 NHS sites; all patients randomised to receive Proton beam therapy will be treated at either UCLH/Christie. Patients will receive treatment for 5 weeks before surgery, and for up to 1 year after surgery. Patients will be followed up at NHS sites for up to 1 year, and then survival data will be collected from NHS Digital for a further 2 years.
What are the possible benefits and risks of participating?
The potential risks and burden will only be applicable to patients randomised to the experimental arm to receive Proton-beam therapy over a period of 3 weeks. Patients on the control arm will be treated as per standard of care. There is a risk of financial burden on patients allocated proton beam therapy who will need to travel to one of the two proton beam centres for their specialised radiotherapy treatment. Patients will be required to organise the travel themselves with the help of their ‘key worker’ from the relevant Proton beam therapy centre. Patients may also be required to stay away from home for 3 weeks if they live far away from one of the 2 proton beam centres. As with any radiotherapy there may be some long-term side effects. The study doctor or nurse will go through these with trial patients and this information is included in the patient information sheet. The adverse events from Proton beam therapy are considered to be low risk, as the concept of Proton beam therapy is to negate the effects of radiation to the healthy tissues surrounding the tumour, mainly healthy lung and heart tissue. The treating team will be monitoring patients for any side effects during and after treatment and will be taking care of any long-term adverse events for up to a year after surgery.
There may be no direct benefit to research participants and this is explained in the patient information sheet. Research participants enrolled in the trial will have a 50% chance of receiving PBT for their oesophageal cancer, which is not currently available off trial, which may or may not improve their survival and quality of life from potentially fewer side effects than standard photon based radiotherapy. With 2 proton beam centres now in England, patients will no longer have to travel overseas for their PBT treatment. Patients in this study will have access to this new treatment, possibly increasing the chances of a long-term cure. Proton beam therapy may make immunotherapy easier to tolerate and possibly more effective. However, none of this is proven and there is no guarantee that individual patients will benefit directly from taking part in this study. We hope the information we gain from the study will benefit people who develop oesophageal cancer in the future. If the trial is a success and shows PBT treatment is better than photon beam radiotherapy then the standard of care may change in future.
Where is the study run from?
University College London (UK)
When is the study starting and how long is it expected to run for?
January 2024 to June 2032
Who is funding the study?
Cancer Research UK
The Taylor Family Foundation (UK)
Who is the main contact?
ctc.protieus@ucl.ac.uk
https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-proton-beam-radiotherapy-for-oesophageal-cancer-and-gastroesophageal-junction
Contact information
Scientific
Cancer Research UK & UCL Cancer Trials Centre, 90 Tottenham Court Road
London
W1T 4TJ
United Kingdom
| Phone | +44 207 679 9608 |
|---|---|
| ctc.protieus@ucl.ac.uk |
Principal Investigator
Department of Medical Physics & Biomedical Engineering Faculty of Engineering Science University College London
London
WC1E 6BT
United Kingdom
 ORCID ID |
0000-0002-6669-0628 |
|---|---|
| Phone | +44 20 7679 0262 Ext: 30262 |
| m.hawkins@ucl.ac.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | A randomised phase 2 trial comparing proton versus photon-based neoadjuvant chemoradiation, followed by adjuvant immunotherapy, in oesophageal cancer |
| Study acronym | PROTIEUS |
| Study objectives | Proton beam therapy given concurrently with chemotherapy before surgery significantly reduces the risk of severe toxicity and prevents delay of post-operative immunotherapy when compared with standard photon radiotherapy for oesophageal cancer. |
| Ethics approval(s) |
Approved 23/01/2024, The London - Camden & Kings Cross Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; +44 207 104 8086; CamdenandKingsCross.REC@hra.nhs.uk), ref: 23/LO/0964 |
| Health condition(s) or problem(s) studied | Oesophageal cancer |
| Intervention | Eligible patients will be allocated by a computer devised programme into one of the treatment groups: A) a group receiving proton beam radiotherapy (PBT) or B) a group receiving standard of care treatment photon radiotherapy. All patients will receive 3 weeks of daily radiation and 5 courses of chemotherapy once weekly, followed by surgery. Patients in PBT group will travel to one of the proton beam centres either in Manchester or London. After chemoradiotherapy, all patients will have surgery and if they have a small amount of remaining cancer cells (residual disease) after surgery, they will receive immunotherapy for up to 1 year after their surgery, approximately 4 to 12 weeks after surgery. The frequency when the patient should receive immunotherapy, for example, once every 2 or 4 weeks, will depend on the local hospital’s policy. After finishing surgery, all patients will be seen at clinic (follow-up visits) at the first month after the surgery, then every 3 months for up to a 1 year. Further follow-up data will be collected remotely via a data collection service called NHS Digital (NHS England data registries). There is also a translational research component where extra blood and tissue samples will be taken from patients. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Frequency and percentage of patients that experience severe post operative complications prior to or at the follow-up assessment 3 months after surgery measured using adverse event data entered on the database by sites which is graded using both the CTCAE and the Clavien Dindo Scale |
| Secondary outcome measures | Preliminary data on longer term efficacy outcomes following 1 year of adjuvant immunotherapy for patients that do not achieve pathologic complete response at surgery measured using survival data and the number and percentages of different types of disease recurrences |
| Overall study start date | 23/01/2024 |
| Completion date | 01/06/2032 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 170; UK Sample Size: 170 |
| Key inclusion criteria | 1. 16 years of age or older 2. Histologically confirmed diagnosis of oesophageal adenocarcinoma (OAC) or squamous cell carcinoma (OSCC) 3. Tumour of the thoracic oesophagus or gastroesophageal junction with distal maximum extension no more than 3 cm beyond the gastroesophageal junction 4. cT stage > = 2 and/or cN stage > = 0-2 defined by AJCC 8th edition 5. ECOG performance status 0–1 6. Suitable for and fit to receive curative neoadjuvant Chemoradiotherapy followed by surgery by an Upper GI MDT 7. Suitable for and fit to receive adjuvant Immunotherapy according to local guidelines 8. Adequate cardiovascular and respiratory function for surgery in the opinion of the surgical team within 4 weeks prior to randomisation 9. Willing and able to give written informed consent and able to comply with treatment and follow up schedule 10. Willing and able to undergo treatment at a PBT centre (i.e. UCLH or The Christie) if randomised to Proton Arm |
| Key exclusion criteria | 1. Metastatic disease or extensive nodal disease (N3). 2. Patients who have had previous treatment for invasive oesophageal carcinoma or gastro-oesophageal junction carcinoma (including Photo Dynamic Therapy or laser therapy for high grade dysplasia/carcinoma in-situ). 3. Patients with > 3cm mucosal extension of tumour into the stomach beyond the GOJ or where the superior extent is in the cervical oesophagus 4. Total length of disease (primary tumour and involved lymph nodes) length > 8 cm 5. Patients with unstable angina, uncontrolled hypertension, cardiac failure or arrhythmia and other clinically significant cardiac disease. 6. Patients with an oesophageal stent (patients requiring a PEG/RIG/feeding jejunostomy for nutritional purposes ARE eligible). 7. No relevant co-morbidities, including Usual Interstitial Pneumonia (UIP) pulmonary fibrosis and connective tissue disorders. 8. History of other malignancy likely to interfere with the protocol treatment (e.g. patients with previously treated malignancy who have been disease-free for < 1 year, or patients with active malignancy undergoing treatment). Exceptions: 8.1. Subjects who have been successfully treated and disease-free for > 3 years, 8.2. A history of treated non-melanoma skin cancer, 8.3. Successfully treated in situ carcinoma, 8.4. CLL in stable remission, or indolent prostate cancer requiring no or only anti-hormonal therapy. 9. Any other situation, which in the opinion of the local PI, makes the patient unsuitable for this trial. 10. Women who are pregnant or breastfeeding. 11. Patients unable to adhere to the contraception guidance in the protocol. |
| Date of first enrolment | 11/06/2024 |
| Date of final enrolment | 01/07/2029 |
Locations
Countries of recruitment
- England
- United Kingdom
- Wales
Study participating centres
London
NW1 2PG
United Kingdom
Sandford Road
Cheltenham
GL53 7AN
United Kingdom
Clatterbridge Road
Bebington
Wirral
CH63 4JY
United Kingdom
London
SE1 7EH
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
Pond Street
London
NW3 2QG
United Kingdom
Tonna Uchaf
Tonna
Neath
SA11 3LX
United Kingdom
Beckett Street
Leeds
LS9 7TF
United Kingdom
Withington
Manchester
M20 4BX
United Kingdom
Mindelsohn Way
Edgbaston
Birmingham
B15 2GW
United Kingdom
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Sponsor information
University/education
Joint Research Office, 4th Floor West, 250 Euston Road
London
NW1 2PG
England
United Kingdom
| Phone | +44 20 3447 9995 |
|---|---|
| ctc.sponsor@ucl.ac.uk | |
| Website | http://www.ucl.ac.uk/ |
"ROR" |
https://ror.org/02jx3x895 |
Funders
Funder type
Charity
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
No information available
Results and Publications
| Intention to publish date | 01/06/2033 |
|---|---|
| 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 | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Editorial Notes
08/11/2024: Cancer Research UK link added to plain English summary field.
11/06/2024: The recruitment start date was changed from 01/06/2024 to 11/06/2024.
14/05/2024: The following changes were made to the study record:
1. The recruitment start date was changed from 01/05/2024 to 01/06/2024.
2. The recruitment end date was changed from 01/06/2029 to 01/07/2029.
3. Wales was added to the countries of recruitment.
4. University Hospitals Bristol and Weston NHS Foundation Trust was removed from the study participating centres.
08/03/2024: A contact was added.
27/12/2023: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
