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

Sponsor

Royal Marsden NHS Foundation Trust (Other)

Overall Status

Unknown status

CT.gov ID

NCT01995942

Collaborator

Pelican Cancer Foundation (Other)

246

Enrollment

Locations

103.9

Anticipated Duration (Months)

12.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	Phase
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

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 Design

Study Type:

Observational

Actual Enrollment :

246 participants

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

Actual Study Start Date :

Jun 7, 2013

Actual Primary Completion Date :

Feb 2, 2017

Anticipated Study Completion Date :

Feb 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Group 1 Patients with mrEMVI positive rectal cancer
Group 2 Patients with mrEMVI negative rectal cancer

Outcome Measures

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. [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. [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). [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.)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria

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

Contacts and Locations

Locations

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