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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Control arm | Other | Management according to national guidelines - conventional MDT, clinical assessment post-treatment planning |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| High resolution MRI scan | Diagnostic Test | MRI reporting of tumour but not mrTRG in the control arm = standard of care |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Up to 5 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 3 years and 5 years |
| To show mrTRG (Tumour Regression Grade) as a measurement tool can be reproduced by appropriately trained radiologists. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Caroline Martin | Contact | +44 (0) 7749 655 817 | cmartin1@imperial.ac.uk | |
| Syvella Ellis | Contact | +44 (0) 7732 315 234 | giclinicaltrials@imperial.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Gina Brown, MD | Imperial College London | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Aberdeen Royal Infirmary - NHS Grampion | Recruiting | Aberdeen | Aberdeenshire | AB252ZN | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28851403 | Derived | 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. |
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| mrTRG assessment | Diagnostic Test | Watch and wait offered for good responders Consider further treatment for poor responders |
|
Agreement between local and centrally measured mrTRG (MRI Tumour Regression Grade) (mrTRG 1 good to mrTRG 5 poor) |
| Up to 2 years |
| Surgical morbidity | Comparison by arm of early (30 day) surgical morbidity according to the Clavien-Dindo classification. | 30 days post operative |
| Surgical morbidity | Comparison by arm of late (up to 12 months) surgical morbidity according to the Clavien-Dindo classification. | 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) | 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 | 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. | 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 | 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 | 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 | Up to 2 years, 3 years and 5 years |
| Hampshire Hospitals NHS Foundation Trust | Recruiting | Basingstoke | Hampshire | RG24 9NA | United Kingdom |
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| University Hospital of North Midlands NHS Trust - Royal Stoke | Recruiting | Stoke-on-Trent | Staffordshire | ST4 6QS | United Kingdom |
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| Salisbury NHS Foundation Trust | Recruiting | Salisbury | Wiltshire | SP2 8BJ | United Kingdom |
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| Bristol Royal Infirmary | Recruiting | Bristol | BS2 8ED | United Kingdom |
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| Colchester General Hospital | Recruiting | Colchester | CO4 5JL | United Kingdom |
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| NHS Lanarkshire - Hairmyres Hospital | Recruiting | East Kilbride | G75 8RG | United Kingdom |
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| Diana Princess of Wales Hospital | Recruiting | Grimsby | DN33 2BA | United Kingdom |
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| University Hospital of North Tees | Recruiting | Stockton-on-Tees | TS19 8PE | United Kingdom |
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| Royal Marsden NHS Foundation Trust | Recruiting | Sutton | SM2 5PT | United Kingdom |
|
| ID | Term |
|---|---|
| D012004 | Rectal Neoplasms |
| ID | Term |
|---|---|
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
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