Trial record 4 of 5541 for:    Open Studies | "Gastrointestinal Diseases"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Royal Marsden NHS Foundation Trust
Sponsor:
Collaborator:
Pelican Cancer Foundation (www.pelicancancer.org)
Information provided by (Responsible Party):
Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01995942
First received: November 21, 2013
Last updated: November 26, 2013
Last verified: July 2013
  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

Resource links provided by NLM:


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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 160
Study Start Date: June 2013
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: June 2018 (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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01995942

Contacts
Contact: Lisa Scerri 0208 915 6067 lisa.scerri@rmh.nhs.uk
Contact: Manish Chand mans001@aol.com

Locations
United Kingdom
University Hospital Southampton NHS Foundation Trust Recruiting
Southampton, Hampshire, United Kingdom, SO16 6YD
Contact: Andrea Lodge       A.Lodge@soton.ac.uk   
Principal Investigator: Alex Mirnezami         
Homerton University Hospital Not yet recruiting
London, Surrey, United Kingdom, E9 6SR
Contact: Eleni Ntala       eleni.ntala@homerton.nhs.uk   
Principal Investigator: Kamini Patel         
Croydon University Hospital Not yet recruiting
Thornton Heath, Surrey, United Kingdom, CR7 7YE
Contact: Yvonne Campbell       Yvonne.Campbell@croydonhealth.nhs.uk   
Contact: Jemma Bhoday       jemmabhoday@doctors.org.uk   
Principal Investigator: Ian Swift         
University Hospital Coventry Not yet recruiting
Coventry, West Midlands, United Kingdom, CV2 2DX
Contact: Maggie Brown       Maggie.Brown@uhcw.nhs.uk   
Principal Investigator: Jane Worlding         
Salisbury District Hospital Not yet recruiting
Salisbury, Wiltshire, United Kingdom, SP2 8BJ
Contact: Julie Atlee       julie.atlee@salisbury.nhs.uk   
Principal Investigator: Graham Branagan         
Royal Marsden Hospital Not yet recruiting
London and Surrey, United Kingdom
Contact: Lisa Scerri    0208 915 6067    lisa.scerri@gmail.com   
Principal Investigator: Gina Brown         
George Eliot Hospital Not yet recruiting
Nuneaton, United Kingdom, CV10 7DJ
Contact: Maggie Brown       maggie.brown@uhcw.nhs.uk   
Principal Investigator: Martin Scott-Brown         
Alexandra Hospital Not yet recruiting
Redditch, United Kingdom, B98 7UB
Contact: Maggie Brown       maggie.brown@uhcw.nhs.uk   
Principal Investigator: Sharmila Sothi         
South Warwickshire NHS Foundation Trust (Warwick Hospital) Not yet recruiting
Warwick, United Kingdom, CV34 5BW
Contact: Maggie Brown       maggie.brown@uhcw.nhs.uk   
Principal Investigator: Peter Correa         
Sponsors and Collaborators
Royal Marsden NHS Foundation Trust
Pelican Cancer Foundation (www.pelicancancer.org)
Investigators
Principal Investigator: Gina Brown Royal Marsden NHS Foundation Trust
  More Information

Additional Information:
No publications provided

Responsible Party: Royal Marsden NHS Foundation Trust
ClinicalTrials.gov Identifier: NCT01995942     History of Changes
Other Study ID Numbers: CCR3873
Study First Received: November 21, 2013
Last Updated: November 26, 2013
Health Authority: United Kingdom: National Research Ethics Service

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

ClinicalTrials.gov processed this record on August 27, 2014