Clinical trial NCT01995942: Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial
Official title: Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: 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
Keywords: Rectal Cancer
EMVI
Extramural Venous Invasion
Microarray
Biomarker
mrEMVI
Tumour Regression Grade
Cancer
Circumferential Resection Margin
CRM
MRI
Radiology
Surgery
Pathology
Lead sponsor: Royal Marsden NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: Pelican Cancer Foundation
First posted: 2013-11-27
Enrollment: 246
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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 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)

Primary outcomes:
measure: The primary endpoint will be time to relapse pertaining to the primary objective of relapse rate at 1 year and 3 years.
timeFrame: 3 years
Secondary outcomes:
measure: 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.
timeFrame: 3 years
measure: 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).
timeFrame: 5 months
Other outcomes:
Locations:
city: Peterborough
country: United Kingdom
facility: Peterborough City Hospital
state: Cambridgeshire
city: Crewe
country: United Kingdom
facility: Leighton Hospital
state: Cheshire
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
state: Cornwall
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Poole
country: United Kingdom
facility: Poole Hospital
state: Dorset
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
city: Crumpsall
country: United Kingdom
facility: North Manchester General Hospital
state: Manchester
city: Wythenshawe
country: United Kingdom
facility: University Hospital of South Manchester
state: Manchester
city: Sutton-in-Ashfield
country: United Kingdom
facility: Kings Mill Hospital
state: Nottinghamshire
city: Burton-on-Trent
country: United Kingdom
facility: Queen's Hospital, Burton Upon Trent
state: Staffordshire
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
state: Surrey
city: London
country: United Kingdom
facility: Homerton University Hospital
state: Surrey
city: Thornton Heath
country: United Kingdom
facility: Croydon University Hospital
state: Surrey
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
state: West Midlands
city: Salisbury
country: United Kingdom
facility: Salisbury District Hospital
state: Wiltshire
city: London And Surrey
country: United Kingdom
facility: Royal Marsden Hospital
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital
city: Redditch
country: United Kingdom
facility: Alexandra Hospital
city: Warwick
country: United Kingdom
facility: South Warwickshire NHS Foundation Trust (Warwick Hospital)
Study officials:
affiliation: Royal Marsden NHS Foundation Trust
name: Gina Brown
role: PRINCIPAL_INVESTIGATOR
References: