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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
441
MRI reporting of tumour but not mrTRG in the control arm = standard of care
Watch and wait offered for good responders Consider further treatment for poor responders
Aberdeen Royal Infirmary - NHS Grampion
Aberdeen, Aberdeenshire, United Kingdom
RECRUITINGHampshire Hospitals NHS Foundation Trust
Basingstoke, Hampshire, United Kingdom
RECRUITINGUniversity Hospital of North Midlands NHS Trust - Royal Stoke
Stoke-on-Trent, Staffordshire, United Kingdom
RECRUITINGSalisbury NHS Foundation Trust
Salisbury, Wiltshire, United Kingdom
RECRUITINGBristol Royal Infirmary
Bristol, United Kingdom
RECRUITINGColchester General Hospital
Colchester, United Kingdom
RECRUITINGNHS Lanarkshire - Hairmyres Hospital
East Kilbride, United Kingdom
RECRUITINGDiana Princess of Wales Hospital
Grimsby, United Kingdom
RECRUITINGUniversity Hospital of North Tees
Stockton-on-Tees, United Kingdom
RECRUITINGRoyal Marsden NHS Foundation Trust
Sutton, United Kingdom
RECRUITINGTo 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.
Time frame: Up to 5 years
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
Time frame: 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)
Time frame: Up to 2 years
Surgical morbidity
Comparison by arm of early (30 day) surgical morbidity according to the Clavien-Dindo classification.
Time frame: 30 days post operative
Surgical morbidity
Comparison by arm of late (up to 12 months) surgical morbidity according to the Clavien-Dindo classification.
Time frame: 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)
Time frame: 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
Time frame: 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.
Time frame: 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
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).
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
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
Correlate ctDNA levels with outcome measures of mrTRG (MRI Tumour Regression Grade) (mrTRG 1 good to mrTRG 5 poor) and survival outcomes
Time frame: Up to 2 years, 3 years and 5 years
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