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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Non Small Cell Lung Cancer, Gastric Adenocarcinoma, Pancreatic Cancer, Gall Bladder Cancer, Bladder Cancer

Intervention / Treatment
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* Diagnostic Test: Oricol Test


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Non-small cell lung cancer<br>A cohort of patients with known NSCLC who are assessed. | Diagnostic Test: Oricol Test<br>* Assessment of rectal mucus for material from aero-digestive cancers.<br>|
| Gastric cancer patient<br>A cohort of patients with known gastric adenocarcinoma who are assessed. | Diagnostic Test: Oricol Test<br>* Assessment of rectal mucus for material from aero-digestive cancers.<br>|
| Pancreatic cancer<br>A cohort of patients with known pancreatic adenocarcinoma who are assessed. | Diagnostic Test: Oricol Test<br>* Assessment of rectal mucus for material from aero-digestive cancers.<br>|
| Urothelial cancers<br>A cohort of patients with known uroepithelial cancers who are assessed. | Diagnostic Test: Oricol Test<br>* Assessment of rectal mucus for material from aero-digestive cancers.<br>|
| Biliary tract cancers<br>A cohort of patients with known biliary tract cancers who are assessed. | Diagnostic Test: Oricol Test<br>* Assessment of rectal mucus for material from aero-digestive cancers.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |