EMVI as a Determinant of Metastasis in Colorectal Cancer (EVIDENCE)

Bowel cancer is the fourth most commonly occurring cancer and the second highest cause of cancer deaths in the UK. Despite advances in treatment, over 40% of patients will die within 5 years. This is normally due to spread of the cancer to other organs (called metastases). Much of the current research focuses on use of additional treatments such as radiotherapy and chemotherapy before or after surgery (adjuvant treatment). It is of vital importance that patients who would benefit from adjuvant treatment can be accurately identified. At the moment, the system used locally to do this places emphasis on the presence of affected lymph nodes (glands). This is because doctors believe that cancer spreads to other organs through the lymphatic system. However, recent studies have suggested that this is not the case.

It is believed that cancer spreads to other organs through the blood stream rather than the lymph node system. This research will look at the genetic material in tumours and metastases as well as in areas of blood vessel invasion and lymph nodes. The analysis will allow us to build a 'family tree' of the tumour and allow us to map the pathway by which the tumour spreads. Tissue samples already collected through a patient's routine care will be used for this study. If the spread through the blood vessels is proven, this would change the way in which patients are selected for treatment and allow development of new treatments to target these pathways.

Study Overview

• Status: Recruiting
• Conditions: Colo-rectal Cancer

Detailed Description

A retrospective ,non-interventional tissue study using archival materials collected through a patient's routine care, EVIDENCE aims to demonstrate that distant metastases in colorectal cancer are related to Extramural Venous Invasion (EMVI) and tumour deposits, not lymph nodes. As EVIDENCE is a retrospective study, there are no time dependent schedules for Case Report Form (CRF) completion or tissue submission.

It will be tested whether the vascular route of spread (as evidenced through EMVI and tumour deposits) is more important than lymph nodes in the development of metastatic disease. The sub-clonal origins of primary colorectal cancers, EMVI, tumour deposits, lymph nodes and distant metastases by reconstructing phylogenetic trees will be compared. A proof for a vascular route of spread rather than lymph nodes would lead to a paradigm shift in future decision making at national and international level.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Caroline Martin; Phone Number: +44 (0) 7749 655 817; Email: c.martin1@imperial.ac.uk
• Study Contact Backup: Name: Syvella Ellis; Phone Number: +44 (0) 7732 315 234; Email: syvella.ellis@imperial.ac.uk

Study Locations

• United Kingdom
  • Hampshire
    • Basingstoke, Hampshire, United Kingdom, RG24 9NA
      • Recruiting
      • Hampshire Hospitals NHS Foundation Trust
      • Contact: Amy Lord, MD; Phone Number: 0784150064; Email: amylord@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients who have undergone a primary resection of their colon or rectum as well as a resection of a distant metastases

Description

Inclusion Criteria:

1. Are aged 16 years or over with colorectal cancer
2. Colon / rectum has been surgically removed
3. Distant metastases has been surgically removed
4. Pre operative staging in the form of CT/MRI has been undertaken and images available for review

Exclusion Criteria:

1. Pathological complete response in the primary tumour
2. Local resection of the primary tumour
3. Inadequate quantity of tissue sample to perform analyses

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of proportion of subjects where Extramural Venous Invasion (EMVI) and tumour deposits vs lymph nodes are associated with distant metastases	Proportion of subjects where EMVI and tumour deposits rather than lymph nodes are associated with distant metastases. This is to determine the route of spread of distant metastases.	1 year from last registered patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of tumour phylogenetic profile between primary tumour, EMVI, tumour deposits, metastases	Comparison of tumour phylogenetic profile between primary tumour, EMVI, tumour deposits, metastases. This is to investigate the clonal origins of metastases in relation to the primary tumour deposits, EMVI and lymph nodes	1 year from last registered patient
Comparison of tumour phylogenes between different metastatic sites and primary tumour	Comparison of tumour phylogenes between different metastatic sites and primary tumour. This is to determine if there are different routes of spread to different organs (i.e. lung, liver, brain, peritoneal)	1 year from last registered patient
Comparison of immunohistochemistry staining profile between primary tumour, EMVI, tumour deposits, metastases	Comparison of immunohistochemistry staining profile between primary tumour, EMVI, tumour deposits, metastases. This is to evaluate the similarities in the immunohistochemistry profile of metastases compared with primary tumour deposits, EMVI and lymph nodes	1 year from last registered patient
Comparison of overall survival based on clonal origins of metastases	Comparison of overall survival based on clonal origins of metastases. This is to investigate the relationship between the clonal origins of metastases and outcomes according to primary tumour deposits, EMVI and lymph nodes	1 year from last registered patient

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Gina Brown, MD, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: October 15, 2024
• First Submitted That Met QC Criteria: October 15, 2024
• First Posted (Actual): October 17, 2024

Study Record Updates

• Last Update Posted (Estimated): November 1, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Colorectal Cancer; Local Advanced Rectal Cancer; Extramural Venous Invasion; Extranodal Tumour Deposits; Imaging and Pathology Biomarkers; Pelvic Recurrence; Metastatic Spread; MRI staging; Phylogenesis; Rectal Cancer Recurrence; Sigmoid Cancer; Surgery for Pelvic Recurrence
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Rectal Neoplasms; Colorectal Neoplasms
• Other Study ID Numbers: DOCUMAS: 22HH7583

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No