Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial (MARVEL)

September 13, 2018 updated by: Royal Marsden NHS Foundation Trust

Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer

Extramural venous invasion (EMVI) is the spread of microscopic tumour cells into the veins around the tumour. Rectal cancer treatment has improved greatly over recent years. However, it is important for us to learn as much about the tumours as possible in order to develop newer therapies. Current treatments may benefit from new genetic information relating to the cancer. We hope to identify genetic differences in certain types of rectal cancer which will allow future treatments.

Study Overview

Detailed Description

Neoadjuvant chemoradiotherapy (CRT) is widely accepted as beneficial to selected patients in terms of decreased risk of local recurrence and overall survival. Current management of rectal cancer involves risk stratification through pre-operative staging leading to formulation of treatment strategy. Very little is known about the long-term outcomes and response to CRT on MRI detected extramural venous invasion (mrEMVI). Although mrEMVI is accepted as a marker of poor prognosis, whether it has a predictive value and should be specifically treated is not known.

Molecular and genetic profiling provides us with an opportunity to understand the underlying mechanisms which govern clinical behaviour in rectal cancer. Using high-throughput technology such as tissue microarray analysis allows large-scale analysis of specimens in a relatively short amount of time. It offers the ability to compare the molecular profiles of different subtypes of rectal cancer such as mrEMVI-positive and -negative tumours and whether any changes are observed following CRT. This can then be correlated with clinical behaviour over the medium and long-term with regards to local recurrence, distant metastases and overall survival.

This study will identify important differences between key rectal cancer tumour subtypes. Identification of reliable pathological markers of EMVI pathways (from both the primary tumour sample, but more importantly from the pre-operative biopsies) has real potential for taking us a step closer to more personalised management of rectal cancer by establishing prognostic biomarkers reflective of disease type, but also through the underlying biology that may be highlighted (with its promise of therapeutic translation).

Study Type

Observational

Enrollment (Actual)

246

Contacts and Locations

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

Study Locations

      • London And Surrey, United Kingdom
        • Royal Marsden Hospital
      • Nuneaton, United Kingdom, CV10 7DJ
        • George Eliot Hospital
      • Redditch, United Kingdom, B98 7UB
        • Alexandra Hospital
      • Warwick, United Kingdom, CV34 5BW
        • South Warwickshire NHS Foundation Trust (Warwick Hospital)
    • Cambridgeshire
      • Peterborough, Cambridgeshire, United Kingdom, PE3 9GZ
        • Peterborough City Hospital
    • Cheshire
      • Crewe, Cheshire, United Kingdom, CW1 4QJ
        • Leighton Hospital
    • Cornwall
      • Truro, Cornwall, United Kingdom, TR1 3LQ
        • Royal Cornwall Hospital
    • Devon
      • Plymouth, Devon, United Kingdom, PL6 8DH
        • Derriford Hospital
    • Dorset
      • Poole, Dorset, United Kingdom, BH15 2JB
        • Poole Hospital
    • Hampshire
      • Southampton, Hampshire, United Kingdom, SO16 6YD
        • University Hospital Southampton NHS Foundation Trust
    • Manchester
      • Crumpsall, Manchester, United Kingdom, M8 5RB
        • North Manchester General Hospital
      • Wythenshawe, Manchester, United Kingdom, M23 9LT
        • University Hospital of South Manchester
    • Nottinghamshire
      • Sutton-in-Ashfield, Nottinghamshire, United Kingdom, NG17 4JL
        • Kings Mill Hospital
    • Staffordshire
      • Burton-on-Trent, Staffordshire, United Kingdom, Burton-on-Trent
        • Queen's Hospital, Burton Upon Trent
    • Surrey
      • Guildford, Surrey, United Kingdom, GU2 7XX
        • Royal Surrey County Hospital
      • London, Surrey, United Kingdom, E9 6SR
        • Homerton University Hospital
      • Thornton Heath, Surrey, United Kingdom, CR7 7YE
        • Croydon University Hospital
    • West Midlands
      • Coventry, West Midlands, United Kingdom, CV2 2DX
        • University Hospital Coventry
    • Wiltshire
      • Salisbury, Wiltshire, United Kingdom, SP2 8BJ
        • Salisbury District Hospital

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 (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients aged over 18 years of age presenting with adenocarcinoma of the rectum. This will be diagnosed on colonoscopy and/or biopsy and MRI, and treatment strategy will include pre-operative CRT followed by surgery.

Description

Inclusion Criteria:

  1. Locally advanced primary rectal cancer (requiring pre-operative treatment); diagnosed on tissue biopsy
  2. Adult patients - over 18 years
  3. Able to undergo curative (TME) surgery
  4. Able to undergo MRI and CT with relevant contrast agent
  5. Able to undergo LCRT

Exclusion Criteria

  1. Metastatic disease at presentation
  2. Emergency diagnosis/treatment
  3. Unable to undergo staging (MRI and CT) or treatment procedures (LCRT/surgery)

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Group 1
Patients with mrEMVI positive rectal cancer
Group 2
Patients with mrEMVI negative rectal cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary endpoint will be time to relapse pertaining to the primary objective of relapse rate at 1 year and 3 years.
Time Frame: 3 years
3 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response rates (in terms of mrTstage, mrN stage, involvement of CRM (circumferential resection margin) and mrTRG (tumour regression grade)) in addition to recurrence rates at 1 year and 3 years.
Time Frame: 3 years
3 years
Measurement of the change in mrEMVI from pre to post pre-operative therapy, will be based on a new proposed EMVI-TRG classification (EMVI TRG 1-5).
Time Frame: 5 months
mrEMVI Regression Grade Scoring Table: Grade 5 - No response (intermediate signal intensity, same appearances as original tumour) Grade 4 - Slight response (little areas of fibrosis or mucin but mostly tumour) Grade 3 - Moderate response (>50% fibrosis or mucin, and visible intermediate signal) Grade 2 - Good response (dense fibrosis; no obvious residual tumour, signifying minimal residual disease or no tumour) Grade 1 - Radiological complete response (rCR) (linear/crescentic 1-2mm scar in mucosa or submucosa only.)
5 months

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Gina Brown, Royal Marsden NHS Foundation Trust

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)

June 7, 2013

Primary Completion (Actual)

February 2, 2017

Study Completion (Anticipated)

February 2, 2022

Study Registration Dates

First Submitted

November 21, 2013

First Submitted That Met QC Criteria

November 26, 2013

First Posted (Estimate)

November 27, 2013

Study Record Updates

Last Update Posted (Actual)

September 14, 2018

Last Update Submitted That Met QC Criteria

September 13, 2018

Last Verified

September 1, 2018

More Information

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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