Magnetic Resonance Tumour Regression Grade (mrTRG) as a Novel Biomarker - Phase III Non CTIMP Trial (TRIGGER)

October 16, 2024 updated by: Imperial College London

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Estimated)

441

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Bristol, United Kingdom, BS2 8ED
        • Recruiting
        • Bristol Royal Infirmary
        • Contact:
        • Principal Investigator:
          • Stephen FALK, MD
      • Colchester, United Kingdom, CO4 5JL
      • East Kilbride, United Kingdom, G75 8RG
      • Grimsby, United Kingdom, DN33 2BA
        • Recruiting
        • Diana Princess of Wales Hospital
        • Contact:
        • Principal Investigator:
          • Rajarshi Roy, MD
      • Stockton-on-Tees, United Kingdom, TS19 8PE
        • Recruiting
        • University Hospital of North Tees
        • Contact:
        • Contact:
        • Principal Investigator:
          • David Wilson, MD
      • Sutton, United Kingdom, SM2 5PT
        • Recruiting
        • Royal Marsden NHS Foundation Trust
        • Principal Investigator:
          • Sheela RAO, MD
        • Contact:
    • Aberdeenshire
      • Aberdeen, Aberdeenshire, United Kingdom, AB252ZN
        • Recruiting
        • Aberdeen Royal Infirmary - NHS Grampion
        • Contact:
        • Contact:
    • Hampshire
      • Basingstoke, Hampshire, United Kingdom, RG24 9NA
        • Recruiting
        • Hampshire Hospitals NHS Foundation Trust
        • Contact:
        • Contact:
        • Principal Investigator:
          • Brendan Moran, MD
        • Sub-Investigator:
          • Mit Dattani, MD
    • Staffordshire
      • Stoke-on-Trent, Staffordshire, United Kingdom, ST4 6QS
    • Wiltshire
      • Salisbury, Wiltshire, United Kingdom, SP2 8BJ

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. MRI defined locally advanced rectal carcinoma i.e. one or more: greater than or equal to mrT3c; mrEMVI positive; mr N1c; mr CRM positive
  2. Biopsy confirmed adenocarcinoma of radiologically defined rectum
  3. Be deemed to require preoperative chemoradiotherapy (CRT) or total neoadjuvant therapy (TNT)

Exclusion Criteria:

  1. Metastatic disease
  2. MRI, radiotherapy and/or chemotherapy contraindications
  3. A post-treatment MRI performed more than 10 weeks after the completion of radiotherapy if given
  4. Previous malignancy within preceding 5 years if risk of recurrence >5%

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Control arm
Management according to national guidelines - conventional MDT, clinical assessment post-treatment planning
Diagnostic test: High resolution MRI scan
MRI reporting of tumour but not mrTRG in the control arm = standard of care
Experimental: Intervention arm
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.
Diagnostic test: High resolution MRI scan
MRI reporting of tumour but not mrTRG in the control arm = standard of care
Diagnostic test: mrTRG assessment
Watch and wait offered for good responders Consider further treatment for poor responders

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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.
Time Frame: Up to 2 years
Agreement between local and centrally measured mrTRG (MRI Tumour Regression Grade) (mrTRG 1 good to mrTRG 5 poor)
Up to 2 years
Surgical morbidity
Time Frame: 30 days post operative
Comparison by arm of early (30 day) surgical morbidity according to the Clavien-Dindo classification.
30 days post operative
Surgical morbidity
Time Frame: 12 months post operative
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
Time Frame: Up to 2 years, 3 years and 5 years
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
Time Frame: Up to 2 years, 3 years and 5 years
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
Time Frame: 1 year, 2 years, 3 years and 5 years
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
Time Frame: Up to 2 years, 3 years and 5 years
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).
Time Frame: Up to 2 years, 3 years and 5 years
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
Time Frame: Up to 2 years, 3 years and 5 years
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Investigators

  • Principal Investigator: Gina Brown, MD, Imperial College London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2016

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2036

Study Registration Dates

First Submitted

February 5, 2016

First Submitted That Met QC Criteria

March 4, 2016

First Posted (Estimated)

March 10, 2016

Study Record Updates

Last Update Posted (Actual)

October 17, 2024

Last Update Submitted That Met QC Criteria

October 16, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DOCUMAS: 23HH8209

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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