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

Neoplasms Clinical Trial

— MARVEL  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01995942
• Other study ID #: CCR3873
• Status: Active, not recruiting
• Start date: June 7, 2013
• Est. completion date: February 2, 2022

Study information

• Verified date: September 2018
• Source: Royal Marsden NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 246
• Est. completion date: February 2, 2022
• Est. primary completion date: February 2, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
United Kingdom	Queen's Hospital, Burton Upon Trent	Burton-on-Trent	Staffordshire
United Kingdom	University Hospital Coventry	Coventry	West Midlands
United Kingdom	Leighton Hospital	Crewe	Cheshire
United Kingdom	North Manchester General Hospital	Crumpsall	Manchester
United Kingdom	Royal Surrey County Hospital	Guildford	Surrey
United Kingdom	Homerton University Hospital	London	Surrey
United Kingdom	Royal Marsden Hospital	London And Surrey
United Kingdom	George Eliot Hospital	Nuneaton
United Kingdom	Peterborough City Hospital	Peterborough	Cambridgeshire
United Kingdom	Derriford Hospital	Plymouth	Devon
United Kingdom	Poole Hospital	Poole	Dorset
United Kingdom	Alexandra Hospital	Redditch
United Kingdom	Salisbury District Hospital	Salisbury	Wiltshire
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton	Hampshire
United Kingdom	Kings Mill Hospital	Sutton-in-Ashfield	Nottinghamshire
United Kingdom	Croydon University Hospital	Thornton Heath	Surrey
United Kingdom	Royal Cornwall Hospital	Truro	Cornwall
United Kingdom	South Warwickshire NHS Foundation Trust (Warwick Hospital)	Warwick
United Kingdom	University Hospital of South Manchester	Wythenshawe	Manchester

Sponsors (2)

Lead Sponsor	Collaborator
Royal Marsden NHS Foundation Trust	Pelican Cancer Foundation

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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).	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

External Links

•   CPMS