Feasibility Study to Investigate Rectal Mucus in Aero-Digestive Tract Cancer.

Pancreatic Cancer Clinical Trial

— ORI-EGI-03  

Official title:

Feasibility Study to Investigate the Genomic and Epigenetic Changes in Rectal Mucus in Non-Colorectal Cancers of the Aero-Digestive Tract (ORI-EGI-03).

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05102110
• Other study ID #: ORICOL-EGI-03
• Status: Recruiting
• Start date: December 1, 2021
• Est. completion date: December 1, 2024

Study information

• Verified date: January 2024
• Source: Origin Sciences
• Contact: Hugo Lywood
• Phone: 01223 750490
• Email: Hugo.lywood[@]originsciences.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of the study is to assess the feasibility of genomic and epigenetic analysis of rectal mucus to detect non-colorectal cancers of the aero- digestive tract using samples collected by the OriCol™ Sampling Device.

The primary objective of the study is to assess whether significant changes in DNA mutation and methylation associated with Non-colorectal cancers of the Aero- digestive Tract (NCRCADT) can be detected in rectal mucus as shed cells and cell-free DNA (cfDNA) pass through the gut and theoretically can be collected from rectal mucus.

Secondary objectives will assess the participant acceptability of the OriCol™ Sampling Device for Upper GI and Lung Pathology as well as contributing to a genomic library collating information about rectal mucus.

Description:

The embryological development of the aero-digestive tract (ADT) is from a single primitive layer, the endoderm. Differentiation of this layer leads to epithelial and mucosal histopathological similarities through a continuous connected lumen extending from the upper third of the oesophagus to the anorectal junction and including the organs of the gastrointestinal tract (liver, pancreas, gallbladder) and the respiratory tract (trachea, bronchi and lung).

Cancers of the aero-digestive tract include; non-small cell lung (NSCLC), distal oesophageal, gastric, pancreatic, biliary, small bowel and colorectal cancer. The predominant type of cancer is an adenocarcinoma arising in the glandular cells lining the viscera. These cells have the capacity to secrete mucus and form the inner lining of the lumen All of these cancers directly or indirectly sheds cells into the gastrointestinal tract. The gastrointestinal epithelium regenerates every 5-7 days, the discarded cellular material migrates distally and is excreted as part of faeces. The majority of lung secretions are swallowed creating an interaction with the intestine which, to date, has primarily been studied from the microbiota perspective.

The Covid-19 pandemic has highlighted the strain on traditional diagnostic pathways, with a drop by 90% of the normal endoscopy workload in the first wave of the pandemic emphasising the need for practical investigations that can be used as a triage tool in primary care to discriminate individuals that do not require more invasive diagnostic tests. Rectal mucus sampling is potentially an appealing screening tool; quick, minimally invasive, cost effective, can be serially repeated for potential prognostic value, requires minimal equipment or training, and produces robust DNA material for extraction.

Recent research has demonstrated that stable, good quantity and quality cfDNA from colorectal cancer can be detected by rectal mucus sampling and clinical trials of the technique in symptomatic participants are underway looking at the use of rectal mucus for detection of colonic cancers (ClinicalTrials.gov, NCT identifier: NCT04659590). This unpublished, research has created a genomic profile of colorectal cancer in the rectal mucus using Next Generation Sequencing (NGS) detection of genetic mutations and alterations in methylation, which correlates with the documented genetic mutations associated with colorectal cancer tumour biopsies. Due to the embryological similarities KRAS and p53 are also found in association with other cancers of the GI tract. Discovered in 1983, methylation is a growing field in epigenetics, it is faster and more cost- effective than genetic mutation detection and promises increased sensitivity and specificity. The literature suggests a strong link between methylation changes and tumuorigenesis in cancers of the aero-digestive tract, which solely, or in conjunction with cf-DNA mutation detection, could play a significant role in early diagnosis.

This research aims to provide a novel insight into rectal mucus. The literature unanimously agrees that further research and standardisation of biomarkers and sampling is required. With novel genomic and epigenetic understanding of diagnostic and therapeutic targets a future of personalised oncological care is anticipated.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 1, 2024
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

Aged 18 years or over Be able to give voluntary, written informed consent to participate in the study

Exclusion Criteria:

Participants with symptoms that would make proctoscopic examination inappropriate, including acute anal fissure, symptomatic thrombosed haemorrhoids or obstructing anorectal lesions as determined by rectal examination Participants with a previous history of cancer Participants who have received previously radiotherapy, chemotherapy or immunotherapy for a malignancy.

Related Conditions & MeSH terms

• Bladder Cancer
• Gall Bladder Cancer
• Gallbladder Neoplasms
• Gastric Adenocarcinoma
• Non Small Cell Lung Cancer
• Pancreatic Cancer
• Urinary Bladder Neoplasms

Intervention

Diagnostic Test:
• Oricol Test
Assessment of rectal mucus for material from aero-digestive cancers.

Locations

Country	Name	City	State
United Kingdom	Royal Devon & Exeter NHS Foundation Trust	Exeter

Sponsors (3)

Lead Sponsor	Collaborator
Origin Sciences	Queen Mary University of London, Royal Devon and Exeter NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Correlation of SNP allele frequency in genes associated with known aero-digestive cancers in paired samples of tumour type and rectal mucus.	Genomic analysis	1 year