New bioMarkers tO straTIfy cOlorectal caNcer Referrals

NCT07035691 | Recruiting

• 2 other identifiers: 321809WT 10042913
• Study Type: observational
• Target: 582
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to evaluate if a blood test for circulating progastrin (hPG80) and transposable elements (TEs) can accurately predict colorectal cancer (CRC) or polyps in adult patients referred to the 2-week wait (2WW) or Straight to Test (STT) pathways for suspected lower gastrointestinal cancer. The main questions it aims to answer are: Can plasma hPG80 levels accurately predict a diagnosis of CRC or polyps in patients undergoing standard 2WW investigations? Can transposable elements (TEs) in the plasma serve as predictive biomarkers for CRC diagnosis in these patients? What are the patient preferences for different diagnostic tests for CRC, particularly a blood-based test compared to more invasive methods? Participants will: Provide a 20ml blood sample during a routine hospital visit for their 2WW diagnostic test (e.g., colonoscopy, CT Colon). Undergo standard clinical investigations as determined by their treating clinicians. Have their final diagnosis (cancer, polyp, or normal) correlated with their plasma hPG80 levels. For a subset of 100 participants (25 with confirmed CRC, 75 non-cancer), have their plasma analyzed for circulating signatures using RNAseq and DNAseq. Complete an electronic post-study questionnaire to explore their preferences and experiences with different CRC diagnostic tests used within the 2WW pathway.

Conditions

Colorectal Carcinoma; Polyp; Colorectal Adenoma

Keywords

Colorectal cancer; Cancer; Polyp; Adenoma; Cancer surveillance; Flag symptoms; Liquid biopsy; Progastrin; Circulating biomarkers; Biomarkers; Risk stratification; Early diagnosis

Outcome Measures

Primary Outcomes (2)

• Predictive value of hPG80 to identify colorectal cancer and adenomatous polyp

  Sensitivity and Specificity of hPG80 to determine colorectal cancer and adenomatous polyp

  From enrollment to 8 weeks (or until the 2WW diagnostic test is completed and the outcome available).

• Identification of Transposable Element (TE) signatures in plasma of colorectal cancer patients

  Expression of transposable element (TE) signatures in the plasma of patients with colorectal cancer and adenomatous polyps compared to healthy controls.

  From enrollment to 8 weeks (or until the 2WW diagnostic test is completed and the outcome available).

Other Outcomes (1)

• Patient preference and choice of diagnostic tests for colorectal cancer

  12 weeks post recruitment date

Study Arms (1)

Patients with flag symptoms referred via 2 week wait pathway to exclude colorectal cancer.

An additional blood sample for the study.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All adult patients who are referred by the GPs to the Barts Health NHS trust under the 2WW referral pathway and the STT pathway would be potentially eligible. We are planning to recruit patients initially only from the Royal London Hospital site and there is potential to expand recruitment to other hospital sites of Barts Health NHS Trust, if necessary.

You may qualify if:

• Adult, lower GI 2WW and or Straight to Test (STT) referral patients with suspected lower GI cancer.
• Male and Female patients aged \>18 years.
• WW referral patients with no history of inflammatory bowel disease.
• Performance status (ECOG 0-2; and 3 pending clinical assessment of fitness).
• Patients with capacity to consent to the study.

You may not qualify if:

• Any patients referred outside of the 2WW and or STT referral pathways with suspected Lower GI cancer or those referred as an emergency with or suspected CRC.
• Age \< 18 years.
• Patients not fit for standard investigations (e.g. not fit for gastroscopy, colonoscopy or CT colonography) in the 2WW pathway.
• Patients with no capacity to consent or who declined consent for participation.
• Patients with untreated solid organ cancers.
• Patients with known inflammatory bowel disease.
• Patients with documented familial type CRC.

Sponsors & Collaborators

• Queen Mary University of London: lead
• Barts & The London NHS Trust: collaborator

Study Sites (1)

Barts Health NHS Trust

London, England, E1 2AT, United Kingdom

RECRUITING

Related Publications (5)

• Reggiardo RE, Maroli SV, Peddu V, Davidson AE, Hill A, LaMontagne E, Aaraj YA, Jain M, Chan SY, Kim DH. Profiling of repetitive RNA sequences in the blood plasma of patients with cancer. Nat Biomed Eng. 2023 Dec;7(12):1627-1635. doi: 10.1038/s41551-023-01081-7. Epub 2023 Aug 31.

  PMID: 37652985 BACKGROUND

• Alix-Panabieres C, Pantel K. Liquid Biopsy: From Discovery to Clinical Application. Cancer Discov. 2021 Apr;11(4):858-873. doi: 10.1158/2159-8290.CD-20-1311.

  PMID: 33811121 BACKGROUND

• Lykoskoufis NMR, Planet E, Ongen H, Trono D, Dermitzakis ET. Transposable elements mediate genetic effects altering the expression of nearby genes in colorectal cancer. Nat Commun. 2024 Jan 25;15(1):749. doi: 10.1038/s41467-023-42405-0.

  PMID: 38272908 BACKGROUND

• Prieur A, Cappellini M, Habif G, Lefranc MP, Mazard T, Morency E, Pascussi JM, Flaceliere M, Cahuzac N, Vire B, Dubuc B, Durochat A, Liaud P, Ollier J, Pfeiffer C, Poupeau S, Saywell V, Planque C, Assenat E, Bibeau F, Bourgaux JF, Pujol P, Sezeur A, Ychou M, Joubert D. Targeting the Wnt Pathway and Cancer Stem Cells with Anti-progastrin Humanized Antibodies as a Potential Treatment for K-RAS-Mutated Colorectal Cancer. Clin Cancer Res. 2017 Sep 1;23(17):5267-5280. doi: 10.1158/1078-0432.CCR-17-0533. Epub 2017 Jun 9.

  PMID: 28600477 BACKGROUND

• You B, Mercier F, Assenat E, Langlois-Jacques C, Glehen O, Soule J, Payen L, Kepenekian V, Dupuy M, Belouin F, Morency E, Saywell V, Flaceliere M, Elies P, Liaud P, Mazard T, Maucort-Boulch D, Tan W, Vire B, Villeneuve L, Ychou M, Kohli M, Joubert D, Prieur A. The oncogenic and druggable hPG80 (Progastrin) is overexpressed in multiple cancers and detected in the blood of patients. EBioMedicine. 2020 Jan;51:102574. doi: 10.1016/j.ebiom.2019.11.035. Epub 2019 Dec 24.

  PMID: 31877416 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood will be collected and plasma separated and frozen. Only plasma will be stored beyond the study under appropriate HTA approval.

MeSH Terms

Conditions

Colorectal Neoplasms; Polyps; Neoplasms; Adenoma; Disease

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Pathologic Processes

Study Officials

• Mohamed A Thaha, MBBS, FRCS, PhD, PGCe Hlt Econ

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valentin Butnari, MBBS, MSc

CONTACT

+442078828747; v.butnari@qmul.ac.uk

Eleanor McAlees

CONTACT

+44 02078828747; e.mcalees@qmul.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2025
• First Posted: June 25, 2025
• Study Start: June 30, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)