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

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01995942
First Posted: November 27, 2013
Last Update Posted: March 9, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Pelican Cancer Foundation
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust
  Purpose
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.

Condition
Adenocarcinoma Rectal Diseases Colorectal Neoplasms Adenocarcinoma, Mucinous Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Neoplasms Neoplasms, Cystic, Mucinous, and Serous Intestinal Neoplasms Gastrointestinal Neoplasms Digestive System Neoplasms Neoplasms by Site Digestive System Diseases Gastrointestinal Diseases Intestinal Diseases

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer

Further study details as provided by Royal Marsden NHS Foundation Trust:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]
  • 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.)


Biospecimen Retention:   Samples With DNA
Histopathology samples taken after rectal tumour removal surgery will be analysed using micrarray techniques. The pathological tissue microarrays (TMAs) will be generated using the Alphelys Tissue Arrayer Minicore®3 system. Markers that will be evaluated will be initially directed at epithelial to mesenchymal (EMT) transition pathways, as our preliminary studies suggest that this phylogenetically conserved molecular program has important roles in tumour dissemination and resistance to conventional chemotherapy.

Enrollment: 246
Actual Study Start Date: June 7, 2013
Estimated Study Completion Date: February 2, 2022
Primary Completion Date: February 2, 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
Group 1
Patients with mrEMVI positive rectal cancer
Group 2
Patients with mrEMVI negative rectal cancer

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).

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01995942


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

Additional Information:
CPMS  This link exits the ClinicalTrials.gov site

Responsible Party: Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01995942     History of Changes
Other Study ID Numbers: CCR3873
First Submitted: November 21, 2013
First Posted: November 27, 2013
Last Update Posted: March 9, 2017
Last Verified: March 2017

Keywords provided by Royal Marsden NHS Foundation Trust:
Rectal Cancer
EMVI
Extramural Venous Invasion
Microarray
Biomarker
mrEMVI
Tumour Regression Grade
Cancer
Circumferential Resection Margin
CRM
MRI
Radiology
Surgery
Pathology

Additional relevant MeSH terms:
Neoplasms
Adenocarcinoma
Rectal Neoplasms
Colorectal Neoplasms
Gastrointestinal Diseases
Digestive System Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Intestinal Diseases
Neoplasms by Histologic Type
Intestinal Neoplasms
Rectal Diseases
Neoplasms, Glandular and Epithelial
Neoplasms, Cystic, Mucinous, and Serous
Adenocarcinoma, Mucinous
Carcinoma
Colonic Diseases