Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer (MARVEL) Trial (MARVEL)
|ClinicalTrials.gov Identifier: NCT01995942|
Recruitment Status : Active, not recruiting
First Posted : November 27, 2013
Last Update Posted : September 14, 2018
|Condition or disease|
|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|
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 Type :||Observational|
|Actual Enrollment :||246 participants|
|Official Title:||Molecular, Pathologic and MRI Investigation of the Prognostic and Redictive Importance of Extramural Venous Invasion in Rectal Cancer|
|Actual Study Start Date :||June 7, 2013|
|Actual Primary Completion Date :||February 2, 2017|
|Estimated Study Completion Date :||February 2, 2022|
Patients with mrEMVI positive rectal cancer
Patients with mrEMVI negative rectal cancer
- 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 ]
- 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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01995942
|Principal Investigator:||Gina Brown||Royal Marsden NHS Foundation Trust|