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NCT Number: NCT02704520

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

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.

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Key information

Conditions

Rectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases Rectal Neoplasms

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Aberdeen Royal Infirmary - NHS Grampion, Aberdeen, Aberdeenshire, United Kingdom

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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)

Exclusion criteria

  • 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%

Treatment and study plan

High resolution MRI scan

Diagnostic Test

MRI reporting of tumour but not mrTRG in the control arm = standard of care

mrTRG assessment

Diagnostic Test

Watch and wait offered for good responders Consider further treatment for poor responders

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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

  2. 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)

  3. Surgical morbidity

    Time frame: 30 days post operative

    Comparison by arm of early (30 day) surgical morbidity according to the Clavien-Dindo classification.

  4. 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.

  5. 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)

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

Study contacts

Contact information is provided by the study sponsor or research team.

Caroline Martin

CONTACT

[email protected]

+44 (0) 7749 655 817

Syvella Ellis

CONTACT

[email protected]

+44 (0) 7732 315 234

Sponsors and collaborators

Lead sponsor

Imperial College London

Other

Registry information

Official study 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

Acronym: TRIGGER

Important dates

Study start
2016
Primary completion
2026
Study completion
2036
First posted
Mar 10, 2016
Registry last updated
Oct 17, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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