Evaluating the performance of a blood test to detect the mechanisms of resistance to trastuzumab therapy in stomach and gullet (gastroesophageal) cancer
| ISRCTN | ISRCTN21998653 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21998653 |
| IRAS number | 278314 |
| Secondary identifying numbers | IRAS 278314 |
- Submission date
- 12/11/2020
- Registration date
- 08/04/2021
- Last edited
- 08/04/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Cancer
Plain English summary of protocol
Background and study aims
HER2-positive cancer is a cancer that has higher than normal levels of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. Patients with HER2-positive cancer are eligible for therapy with the drug trastuzumab (also named Herceptin). Trastuzumab can help control the growth of cancer cells containing high amounts of HER2. However, trastuzumab resistance can occur and the cancer that has been responding to the therapy starts to resist the effects of the therapy and begins to grow (disease progression). When this happens, alternative therapies and management need to be discussed. To select the most appropriate treatment, the precise resistance mechanisms in each patient’s cancer need to be identified. This can be achieved by analysing the DNA of tumour tissue obtained via biopsy. But this procedure is invasive and often not possible. Recently, a new test that requires a blood sample has been developed. It is called a liquid biopsy and it uses the pieces of DNA from tumour cells that are in the bloodstream. The aim of the REGAL study is to evaluate the performance of liquid biopsies in detecting the mechanisms of trastuzumab resistance in HER2 positive gastroesophageal cancers and to assess if liquid biopsies could be an alternative to tissue biopsies. This would provide a less invasive and more useful test that could be used to closely monitor patients on treatment.
Who can participate?
Patients diagnosed with a HER2 positive oesophageal or stomach cancer and being offered the therapy combining trastuzumab and chemotherapy.
What does the study involve?
Blood samples will be collected at the start of the trastuzumab and chemotherapy. If there is evidence the cancer is resisting the trastuzumab and chemotherapy (disease progression), another blood sample will be collected at this time. Optionally, if the participant is willing to, tumour tissue samples will also be collected at the same times. We will analyse the DNA contained in the blood samples to see if information about any mechanisms of resistance can be detected and if this information is concordant with information from tissue biopsies.
What are the possible benefits and risks of participating?
There is no apparent direct benefit in taking part in the research. However, the information obtained from this study will be extremely useful to assess the clinical value of liquid biopsy. What is learnt from this study could benefit patients with the same type of cancer in the future. There is no risk associated with the blood sampling procedure. The samples will be collected at the same time as participants undergo routine blood tests, so it will not require additional needles for blood collection. For tissue biopsy samples (optional), wherever possible, they will be collected when the participants undergo biopsy procedures as part of their routine care. If not possible, then the biopsies will be carried out for the study purpose only. Collecting these tissue specimens is considered safe, but the possible risks include bleeding, infection and pain at the time the samples are removed. Such complications are reported in 1 in 1000 endoscopic biopsies and in less than 1 in 100 CT-guided biopsies.
Where is the study run from?
University of Dundee School of Medicine (UK)
When is the study starting and how long is it expected to run for?
October 2020 to October 2022
Who is funding the study?
The University of Dundee (UK)
Who is the main contact?
Professor Russell Petty
r.petty@dundee.ac.uk
Contact information
Scientific
Ninewells Hospital and Medical school
University of Dundee
James Arnott Drive
Dundee
DD1 9SY
United Kingdom
| Phone | +44 (0)1382383542 / +44 (0)1382383125 |
|---|---|
| r.petty@dundee.ac.uk |
Public
Ninewells Hospital and Medical school
University of Dundee
James Arnott Drive
Dundee
DD1 9SY
United Kingdom
| Phone | +44 (0)1382383542 / +44 (0)1382383125 |
|---|---|
| r.petty@dundee.ac.uk |
Study information
| Study design | Multicentre observational study with longitudinal specimen collection |
|---|---|
| Primary study design | Observational |
| Secondary study design | Longitudinal study |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | Capturing trastuzumab REsistance in Gastroesophageal Adenocarcinoma by Liquid biopsy |
| Study acronym | REGAL |
| Study objectives | Liquid biopsies analyses can be used to capture the molecular mechanisms of trastuzumab resistance in advanced HER2 positive gastroesophageal adenocarcinoma. |
| Ethics approval(s) | Approved 29/10/2020, East of Scotland Research Ethics Service (Tayside medical Science Centre, Residency Block Level 3, George Pirie Way, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK; +44 (0)1382 383848; tay.eosres@nhs.scot), ref 20/ES/0090 |
| Health condition(s) or problem(s) studied | Advanced HER2 positive gastroesophageal adenocarcinoma |
| Intervention | Blood samples will be collected from participants at the start of the chemotherapy + trastuzumab therapy and will be analysed by NGS to capture the molecular mechanisms involved in trastuzumab resistance. Tissue biopsies of primary tumour and metastatic sites will be also be collected from patients who are willing (optional) and profiled by NGS. This is to confirm the clinical relevance of ctDNA analysis by comparison with standard tumour tissue analysis. |
| Intervention type | Genetic |
| Primary outcome measure | Detection at relapse of molecular abnormalities related to trastuzumab resistance by ctDNA profiling of biopsy taken at a single time point |
| Secondary outcome measures | Using biopsy taken at a single time point: 1. Detection of molecular abnormalities using liquid biopsy 2. Detection of molecular abnormalities using the standard of care tissue biopsy analysis 2. Identification of new or known resistance-related gene variants using next generation sequencing-based ctDNA profiling and definition of a correlation between the genotype of the primary tumour and the emergence of molecularly different clones |
| Overall study start date | 01/10/2019 |
| Completion date | 01/10/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 25 |
| Key inclusion criteria | 1. Aged 18 years or older 2. Willing to provide written informed consent 3. Diagnosed with histologically confirmed locally advanced or metastatic HER2 positive gastroesophageal adenocarcinoma 4. Subject is being considered for treatment with the standard of care platinum fluoropyrimidine combination chemotherapy plus trastuzumab therapy and is willing and able to proceed with this treatment 5. Subject is able to provide whole blood at baseline visit and final visit |
| Key exclusion criteria | 1. Any medical or mental condition that would interfere with the subject’s ability to willingly give written informed consent 2. Any significant medical condition that in the opinion of the chief investigator would impair the ability of the participant to complete the requirements of the protocol |
| Date of first enrolment | 01/12/2020 |
| Date of final enrolment | 01/10/2022 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Dundee
DD1 9SY
United Kingdom
Belfast
BT9 7JL
United Kingdom
CF14 2TL
United Kingdom
Edinburgh
EH4 2XU
United Kingdom
Glasgow
G12 0YN
United Kingdom
Leeds
LS9 7TF
United Kingdom
Sponsor information
University/education
TASC
Ninewells Hospital and Medical School
Residency Block
Level 3
George Pirie Way
Dundee
DD1 9SY
Scotland
United Kingdom
| Phone | +44 (0)1382 383877 |
|---|---|
| tascgovernance@dundee.ac.uk | |
| Website | http://www.dundee.ac.uk/ |
"ROR" |
https://ror.org/03h2bxq36 |
Funders
Funder type
Hospital/treatment centre
No information available
Results and Publications
| Intention to publish date | 01/03/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Stored in repository |
| Publication and dissemination plan | Planned publication in a leading peer-reviewed journal. |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
17/11/2020: Trial’s existence confirmed by East of Scotland Research Ethics Service.
