Rectal CancerTRIGGERNCT02704520
Magnetic Resonance Tumour Regression Grade (mrTRG) as a Novel Biomarker - Phase III Non CTIMP Trial
A study testing High resolution MRI scan and mrTRG assessment in people with Rectal Cancer, run by Imperial College London at 10 sites in United Kingdom.
Trial summary
Open to patients undergoing any pre-operative treatment for locally advanced rectal cancer, TRIGGER is the only phase III clinical trial in the UK offering watch and wait. All patients will have post treatment MRI scans routinely performed, no change from the MERCURY trials high resolution MRI protocol is required. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- High resolution MRI scan and mrTRG assessment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 441 participants
- Where
- 10 sitesUnited Kingdom
- Study dates
- Mar 2016to Dec 2036
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- MRI defined locally advanced rectal carcinoma i.e. one or more: greater than or equal to mrT3c; mrEMVI positive; mr N1c; mr CRM positive
- Biopsy confirmed adenocarcinoma of radiologically defined rectum
- Be deemed to require preoperative chemoradiotherapy (CRT) or total neoadjuvant therapy (TNT)
Who cannot join
- Metastatic disease
- MRI, radiotherapy and/or chemotherapy contraindications
- A post-treatment MRI performed more than 10 weeks after the completion of radiotherapy if given
- Previous malignancy within preceding 5 years if risk of recurrence >5%
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
United Kingdom10 sites, 10 recruiting
- Recruiting
Aberdeen Royal Infirmary - NHS Grampion
Aberdeen, Aberdeenshire, AB252ZN
Angela Cheyne, 01224 554870, angela.cheyne@nhs.net
Sue Rodwell, 01224 553830, s.rodwell@nhs.net
- Recruiting
Hampshire Hospitals NHS Foundation Trust
Basingstoke, Hampshire, RG24 9NA
Megan Topping, 01256 313918, megan.topping@hhft.nhs.uk
Caroline Palmer, 01256 313918, caroline.palmer@hhft.nhs.uk
- Recruiting
Bristol Royal Infirmary
Bristol, BS2 8ED
Robert Hollister, +44 1173426742, robert.hollister@uhbristol.nhs.uk
Stephen Falk, MD
- Recruiting
Colchester General Hospital
Colchester, CO4 5JL
Lucy Thorogood, +44 1206 745 355, lucy.thorogood@colchesterhospital.nhs.uk
Celine Driscoll, +44 1206 745 355, celine.driscoll@colchesterhospital.nhs.uk
- Recruiting
NHS Lanarkshire - Hairmyres Hospital
East Kilbride, G75 8RG
Louise Devlin, +44 1355 585329, louise.devlin@lanarkshire.scot.nhs.uk
Angela Scullion, +44 1355 585 329, angela.scullion@lanarkshire.scot.nhs.uk
- Recruiting
Diana Princess of Wales Hospital
Grimsby, DN33 2BA
Jonathan Hatton, +44 3033 303555, jonathan.hatton@nhs.net
Rajarshi Roy, MD
- Recruiting
Salisbury NHS Foundation Trust
Salisbury, Wiltshire, SP2 8BJ
Sophia Strong-Sheldrake, 01722 336262 ext. 4191, sophia.strong-sheldrake@salisbury.nhs.uk
Julie Attlee, 01722 336262 ext. 4191, julie.attlee@salisbury.nhs.uk
- Recruiting
University Hospital of North Tees
Stockton-on-Tees, TS19 8PE
Helen Wilson, +44 1642 383 277, Helen.Wilson2@nth.nhs.uk
Lynda Poole, +44 1642 383 277, Lynda.Poole@nth.nhs.uk
- Recruiting
University Hospital of North Midlands NHS Trust - Royal Stoke
Stoke-on-Trent, Staffordshire, ST4 6QS
Katrina Parkinson, 01782 672621, katrina.parkinson@uhnm.nhs.uk
Angela Peake, 01782 672258, angela.peake@uhnm.nhs.uk
- Recruiting
Royal Marsden NHS Foundation Trust
Sutton, SM2 5PT
Cordelia Grant, cordelia.grant@rmh.nhs.uk
Sheela Rao, MD
About this study
Official title: Magnetic Resonance Tumour Regression Grade (mrTRG) as a Novel Biomarker to Stratify Management of Good and Poor Responders to Radiotherapy: A Rectal Cancer Multicentre Randomised Control Trial to Avoid Surgery With 'Watch and Wait' or Intensify Treatment According to mrTRG
Open to patients undergoing any pre-operative treatment for locally advanced rectal cancer, TRIGGER is the only phase III clinical trial in the UK offering watch and wait. All patients will have post treatment MRI scans routinely performed, no change from the MERCURY trials high resolution MRI protocol is required. Patients will be randomised to either the control arm for management according to national guidelines - conventional MDT, clinical assessment post-treatment planning using the baseline MRI. Patients in the interventional arm will have their post treatment MRI scans read by a radiologist trained and supported to reliably report the mrTRG grade and have their management directed accordingly - 'Good response' (mrTRG 1\&2) - watch and wait (avoidance of surgery) offered. 'Poor response' (mrTRG 3-5) - local colorectal MDT is informed and uses information to discuss and agree next steps in treatment and surveillance. Patients are followed up for five years with QoL questionnaires completed at registration, 3 and 5 years.
Read the detailed description
The only phase III clinical trial in the UK offering watch and wait, the TRIGGER trial aims to validate mrTRG as an imaging biomarker for the stratified management of patients with locally advanced rectal cancer. The 'good responders' (mrTRG1\&2) often have no evidence of tumour and it may be possible to avoid surgery in this group and so maintaining QoL while not impacting survival rates. The 'poor responders' (mrTRG3-5) are at high risk of poor oncological outcomes and this knowledge is useful in planning ongoing treatment and surveillance.
TRIGGER is now a non-cTIMP trial as the protocol does not specify chemotherapy or IMP treatments. Decisions about the use of chemotherapy will be based upon local MDT discussions as is normal practice and national policy and the trial CRFs will capture these decisions and whether more treatment is given to patients or not. TRIGGER does not mandate or recommend the use of any treatments: specifically it does not suggest the use of investigational medicinal products. If any centre wishes to use IMPs this would be in the context of separate trial protocols and would not preclude entry into TRIGGER.
- Conditions
- Rectal Cancer
- Being tested
- High resolution MRI scan, mrTRG assessment
- Keywords
- Rectal Cancer, Magnetic Resonance Imaging, Chemoradiotherapy, Chemotherapy, Diagnostic Imaging
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High resolution MRI scanDiagnostic test
MRI reporting of tumour but not mrTRG in the control arm = standard of care
mrTRG assessmentDiagnostic test
Watch and wait offered for good responders Consider further treatment for poor responders
| Study group | Role | What they receive |
|---|---|---|
| Control arm | Other | Management according to national guidelines - conventional MDT, clinical assessment post-treatment planning Receives: Diagnostic Test: High resolution MRI scan |
| Intervention arm | Experimental | mrTRG directed management 'Good response' (mrTRG 1\&2) - deferral of surgery (watch \& wait) offered. 'Poor response' (mrTRG 3-5) - local colorectal MDT is informed and uses information to discuss and agree next steps in treatment and surveillance. Receives: Diagnostic Test: High resolution MRI scan; Diagnostic Test: mrTRG assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
To show that patients can successfully avoid surgery after achieving a good response to treatment as measured on MRI (mrTRG).
Non-inferiority of overall survival at 3 years for the mrTRG (MRI Tumour Regression Grade) good response group (mrTRG 1 and 2) compared with control.
Measured: Up to 5 years
Secondary outcomes (10)
To describe the prognostic features associated with good and poor response to treatment as measured by MRI (mrTRG)
Correlation of baseline and post treatment prognostic factors on imaging and pathology against survival outcomes
Measured: 3 years and 5 years
To show mrTRG (Tumour Regression Grade) as a measurement tool can be reproduced by appropriately trained radiologists.
Agreement between local and centrally measured mrTRG (MRI Tumour Regression Grade) (mrTRG 1 good to mrTRG 5 poor)
Measured: Up to 2 years
Surgical morbidity
Comparison by arm of early (30 day) surgical morbidity according to the Clavien-Dindo classification.
Measured: 30 days post operative
Surgical morbidity
Comparison by arm of late (up to 12 months) surgical morbidity according to the Clavien-Dindo classification.
Measured: 12 months post operative
To investigate the effect of the preoperative treatment regime on mrTRG measurement
Reporting of treatment given against measurement of mrTRG (MRI Tumour Regression Grade) response (mrTRG 1 good to mrTRG 5 poor)
Measured: Up to 2 years, 3 years and 5 years
To investigate the effect of the preoperative treatment regime on survival outcomes
Reporting of treatment given survival outcomes
Measured: Up to 2 years, 3 years and 5 years
To investigate the effect of mrTRG directed treatment strategy on Quality of Life
Quality of life assessed using EORTC QLQ-C30, EQ-5D and Low Anterior Resection Syndrome Score (LARS).scans performed at baseline, post-CRT and during surveillance schedule.
Measured: 1 year, 2 years, 3 years and 5 years
To investigate the economic impact of introducing an mrTRG directed treatment strategy
Healthcare costs using NHS Reference Costs combined with health resource utilization and QoL data
Measured: Up to 2 years, 3 years and 5 years
To define molecular and immunological characteristics associated with treatment response as measured by MRI (mrTRG).
Correlate molecular and immunological biomarkers with outcome measures of mrTRG (MRI Tumour Regression Grade) response, (mrTRG 1 good to mrTRG 5 poor) and survival outcomes
Measured: Up to 2 years, 3 years and 5 years
To assess whether the detection of ctDNA predicts for relapse in patients with locally advanced rectal cancer
Correlate ctDNA levels with outcome measures of mrTRG (MRI Tumour Regression Grade) (mrTRG 1 good to mrTRG 5 poor) and survival outcomes
Measured: Up to 2 years, 3 years and 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2016 (estimated)
- Study startMar 2016
- Primary completionDec 2026 (estimated)
- Study completionDec 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 441 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gina Brown, MD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02704520
- Sponsor's protocol ID
- DOCUMAS: 23HH8209
- Acronym
- TRIGGER
- Status last verified
- Oct 2024
- First submitted
- 5 Feb 2016
- Last updated
- 17 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Battersby NJ, Dattani M, Rao S, Cunningham D, Tait D, Adams R, Moran BJ, Khakoo S, Tekkis P, Rasheed S, Mirnezami A, Quirke P, West NP, Nagtegaal I, Chong I, Sadanandam A, Valeri N, Thomas K, Frost M, Brown G. A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial. Trials. 2017 Aug 29;18(1):394. doi: 10.1186/s13063-017-2085-2.
PubMed 28851403
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Magnetic Resonance Tumour Regression Grade (mrTRG) as a Novel Biomarker to Stratify Management of Good and Poor Responders to Radiotherapy: A Rectal Cancer Multicentre Randomised Control Trial to Avoid Surgery With 'Watch and Wait' or Intensify Treatment According to mrTRG
- ClinicalTrials.gov ID
- NCT02704520
- Acronym / sponsor ID
- TRIGGER / DOCUMAS: 23HH8209
- Conditions
- Rectal Cancer
- Keywords
- Rectal Cancer, Magnetic Resonance Imaging, Chemoradiotherapy, Chemotherapy, Diagnostic Imaging
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 441 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Mar 2016 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2036 (estimated)
- First posted
- 10 Mar 2016 (estimated)
- 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.
Open to patients undergoing any pre-operative treatment for locally advanced rectal cancer, TRIGGER is the only phase III clinical trial in the UK offering watch and wait. All patients will have post treatment MRI scans routinely performed, no change from the MERCURY trials high resolution MRI protocol is required. Patients will be randomised to either the control arm for management according to national guidelines - conventional MDT, clinical assessment post-treatment planning using the baseline MRI. Patients in the interventional arm will have their post treatment MRI scans read by a radiologist trained and supported to reliably report the mrTRG grade and have their management directed accordingly - 'Good response' (mrTRG 1\&2) - watch and wait (avoidance of surgery) offered. 'Poor response' (mrTRG 3-5) - local colorectal MDT is informed and uses information to discuss and agree next steps in treatment and surveillance. Patients are followed up for five years with QoL questionnaires completed at registration, 3 and 5 years.
Detailed description
The only phase III clinical trial in the UK offering watch and wait, the TRIGGER trial aims to validate mrTRG as an imaging biomarker for the stratified management of patients with locally advanced rectal cancer. The 'good responders' (mrTRG1\&2) often have no evidence of tumour and it may be possible to avoid surgery in this group and so maintaining QoL while not impacting survival rates. The 'poor responders' (mrTRG3-5) are at high risk of poor oncological outcomes and this knowledge is useful in planning ongoing treatment and surveillance.
TRIGGER is now a non-cTIMP trial as the protocol does not specify chemotherapy or IMP treatments. Decisions about the use of chemotherapy will be based upon local MDT discussions as is normal practice and national policy and the trial CRFs will capture these decisions and whether more treatment is given to patients or not. TRIGGER does not mandate or recommend the use of any treatments: specifically it does not suggest the use of investigational medicinal products. If any centre wishes to use IMPs this would be in the context of separate trial protocols and would not preclude entry into TRIGGER.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control arm | Other | Diagnostic Test: High resolution MRI scanManagement according to national guidelines - conventional MDT, clinical assessment post-treatment planning |
| Intervention arm | Experimental | Diagnostic Test: High resolution MRI scan, Diagnostic Test: mrTRG assessmentmrTRG directed management 'Good response' (mrTRG 1\&2) - deferral of surgery (watch \& wait) offered. 'Poor response' (mrTRG 3-5) - local colorectal MDT is informed and uses information to discuss and agree next steps in treatment and surveillance. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- MRI defined locally advanced rectal carcinoma i.e. one or more: greater than or equal to mrT3c; mrEMVI positive; mr N1c; mr CRM positive
- Biopsy confirmed adenocarcinoma of radiologically defined rectum
- Be deemed to require preoperative chemoradiotherapy (CRT) or total neoadjuvant therapy (TNT)
Key exclusion criteria (4 listed)
- Metastatic disease
- MRI, radiotherapy and/or chemotherapy contraindications
- A post-treatment MRI performed more than 10 weeks after the completion of radiotherapy if given
- Previous malignancy within preceding 5 years if risk of recurrence >5%
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 |
|---|---|---|
| High resolution MRI scanMRI reporting of tumour but not mrTRG in the control arm = standard of care | Diagnostic test | Control arm, Intervention arm |
| mrTRG assessmentWatch and wait offered for good responders Consider further treatment for poor responders | Diagnostic test | Intervention arm |
Primary outcome
To show that patients can successfully avoid surgery after achieving a good response to treatment as measured on MRI (mrTRG).
Time frame: Up to 5 years
Non-inferiority of overall survival at 3 years for the mrTRG (MRI Tumour Regression Grade) good response group (mrTRG 1 and 2) compared with control.
10 secondary outcomes
To describe the prognostic features associated with good and poor response to treatment as measured by MRI (mrTRG)
Time frame: 3 years and 5 years
To show mrTRG (Tumour Regression Grade) as a measurement tool can be reproduced by appropriately trained radiologists.
Time frame: Up to 2 years
Surgical morbidity
Time frame: 30 days post operative
Surgical morbidity
Time frame: 12 months post operative
To investigate the effect of the preoperative treatment regime on mrTRG measurement
Time frame: Up to 2 years, 3 years and 5 years
To investigate the effect of the preoperative treatment regime on survival outcomes
Time frame: Up to 2 years, 3 years and 5 years
To investigate the effect of mrTRG directed treatment strategy on Quality of Life
Time frame: 1 year, 2 years, 3 years and 5 years
To investigate the economic impact of introducing an mrTRG directed treatment strategy
Time frame: Up to 2 years, 3 years and 5 years
To define molecular and immunological characteristics associated with treatment response as measured by MRI (mrTRG).
Time frame: Up to 2 years, 3 years and 5 years
To assess whether the detection of ctDNA predicts for relapse in patients with locally advanced rectal cancer
Time frame: Up to 2 years, 3 years and 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2024.
- Derived from this study: PubMed 28851403Battersby NJ, Dattani M, Rao S, Cunningham D, Tait D, Adams R, Moran BJ, Khakoo S, Tekkis P, Rasheed S, Mirnezami A, Quirke P, West NP, Nagtegaal I, Chong I, Sadanandam A, Valeri N, Thomas K, Frost M, Brown G. A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial. Trials. 2017 Aug 29;18(1):394. doi: 10.1186/s13063-017-2085-2.
- Individual participant dataSharing planned: No
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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.
Gina Brown, MD principal investigator
Imperial College London
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High resolution MRI scan and mrTRG assessment in people with Rectal Cancer, run by Imperial College London at 10 sites 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 3 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 17 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Caroline Martin (+44 (0) 7749 655 817, cmartin1@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To show that patients can successfully avoid surgery after achieving a good response to treatment as measured on MRI (mrTRG). (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02704520, which also lists 1 linked publication.
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 17 Oct 2024.