Early Onset Colorectal Cancer Detection

Colorectal Cancer Clinical Trial

— ENCODE  

Official title:

Development and Validation fo an Exosome-Based and Machine Learning Powered Liquid Biopsy for the Detection of Early-Onset Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06342401
• Other study ID #: 23228/ENCODE
• Status: Recruiting
• Start date: April 15, 2023
• Est. completion date: October 15, 2025

Study information

• Verified date: April 2024
• Source: City of Hope Medical Center
• Contact: Ajay Goel, PhD
• Phone: 626-218-3452
• Email: AJGOEL[@]COH.ORG
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Colorectal cancer (CRC) once predominantly affected older individuals, but in recent years has witnessed a progressive increase in incidence among young adults. Once rare, early-onset colorectal cancer (EOCRC, that is, a CRC diagnosed before the age of 50) now constitutes 10-15% of all newly diagnosed CRC cases and it stands as the first cause of cancer-related death in young men and the second for young women.

This study aims to detect EOCRC with a non-invasive test, using a blood-based molecular assay based on microRNA (ribonucleic acid)

Description:

The rising incidence of early-onset colorectal cancer (EOCRC) is a pressing clinical issue unique to our times, and it is expected to grow with an anticipated further 90% increase in incidence by the decade's end. Challenges persist even after reducing the CRC screening age to 45: under-45s lack routine screening and compliance in the 45-50 age group remains low, partly due to invasiveness and discomfort of standard screening methods. Urgent action is warranted to develop affordable, sensitive, and feasible screening for timely detection and improved participation. A non-invasive, patient-friendly screening test, like a blood-based assay, could address these epidemiological concerns and also attract underserved populations.

This study involves the development and validation of a liquid biopsy, assessing circulating cell-free and exosomal microRNAs (cf-miRNA and exo-miRNA, respectively) for indirect sampling of tumor tissue in the bloodstream. The researchers intend to harness machine learning and bioinformatics to create an integrated panel (with both cf-miRNAs and exo-miRNAs) to enhance the inherently high sensitivity of cf-miRNAs with the distinctive specificity of exo-miRNAs. This combined approach will not only improve the performance of a diagnostic model but will also tap into the diverse tumor biology aspects of EOCRC.

The study's core goal is to develop cost-efficient, non-invasive, clinic-friendly biomarkers with high sensitivity and specificity, aiding EOCRC detection.

The researchers intend to do so in three phases:

1. To perform comprehensive small RNA-Seq from matched cf-miRNA, exo-miRNA, cancer-derived miRNA, and mucosa-derived miRNA.

2. To develop and train two miRNA detection panels (cf-miRNA and exo-miRNA, respectively) based on advanced machine-learning models and, then, combine these two using several machine-learning models to obtain a final detection biomarker.

3. To validate the findings in an independent cohort of EOCRC and controls.

In summary, this proposal promises to improve patient care and compliance, and, ultimately, reduce mortality from EOCRC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: October 15, 2025
• Est. primary completion date: April 15, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Stage I, II, III, IV colorectal cancer (TNM classification, 8th edition) diagnosed before the age of 50 (EOCRC cases)

• Received standard diagnostic and staging procedures as per local guidelines, and at least one sample was drawn before receiving any curative-intent treatment

• Colonoscopy-proven cancer-free status at the time of study inclusion (Non-disease controls)

Exclusion Criteria:

• Hereditary colorectal cancer syndromes (identified through genetic testing)

• Inflammatory bowel diseases

• Lack of written informed consent

Related Conditions & MeSH terms

• Colorectal Adenocarcinoma
• Colorectal Cancer
• Colorectal Cancer Stage I
• Colorectal Cancer Stage II
• Colorectal Cancer Stage III
• Colorectal Cancer Stage IV
• Colorectal Neoplasms
• Colorectal Neoplasms Malignant
• Neoplasms

Intervention

Diagnostic Test:
• ENCODE
A panel of microRNA, both cell-free and exosomes, whose expression level is tested from plasma samples from patients with early onset colorectal cancer and non-disease controls.

Locations

Country	Name	City	State
Italy	IRCCS San Raffaele	Milan
Japan	Kawasaki University	Kawasaki
Japan	Mie University	Mie
Japan	National Cancer Center Hospital	Tokyo
Japan	Tokyo Medical and Dental University	Tokyo
Japan	Yamagata University	Yamagata
Spain	Barcelona University	Barcelona
Spain	University of La Laguna	La Laguna
Spain	Salamanca Biomedical Research Institute	Madrid
United States	City of Hope Medical Center	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
City of Hope Medical Center

Countries where clinical trial is conducted

United States,  Italy,  Japan,  Spain, 

References & Publications (10)

Akimoto N, Ugai T, Zhong R, Hamada T, Fujiyoshi K, Giannakis M, Wu K, Cao Y, Ng K, Ogino S. Rising incidence of early-onset colorectal cancer - a call to action. Nat Rev Clin Oncol. 2021 Apr;18(4):230-243. doi: 10.1038/s41571-020-00445-1. Epub 2020 Nov 20. — View Citation

Boardman LA, Vilar E, You YN, Samadder J. AGA Clinical Practice Update on Young Adult-Onset Colorectal Cancer Diagnosis and Management: Expert Review. Clin Gastroenterol Hepatol. 2020 Oct;18(11):2415-2424. doi: 10.1016/j.cgh.2020.05.058. Epub 2020 Jun 7. — View Citation

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum In: CA Cancer J Clin. 2020 Jul;70(4):313. — View Citation

Cavestro GM, Mannucci A, Balaguer F, Hampel H, Kupfer SS, Repici A, Sartore-Bianchi A, Seppala TT, Valentini V, Boland CR, Brand RE, Buffart TE, Burke CA, Caccialanza R, Cannizzaro R, Cascinu S, Cercek A, Crosbie EJ, Danese S, Dekker E, Daca-Alvarez M, Deni F, Dominguez-Valentin M, Eng C, Goel A, Guillem JG, Houwen BBSL, Kahi C, Kalady MF, Kastrinos F, Kuhn F, Laghi L, Latchford A, Liska D, Lynch P, Malesci A, Mauri G, Meldolesi E, Moller P, Monahan KJ, Moslein G, Murphy CC, Nass K, Ng K, Oliani C, Papaleo E, Patel SG, Puzzono M, Remo A, Ricciardiello L, Ripamonti CI, Siena S, Singh SK, Stadler ZK, Stanich PP, Syngal S, Turi S, Urso ED, Valle L, Vanni VS, Vilar E, Vitellaro M, You YN, Yurgelun MB, Zuppardo RA, Stoffel EM; Associazione Italiana Familiarita Ereditarieta Tumori; Collaborative Group of the Americas on Inherited Gastrointestinal Cancer; European Hereditary Tumour Group, and the International Society for Gastrointestinal Hereditary Tumours. Delphi Initiative for Early-Onset Colorectal Cancer (DIRECt) International Management Guidelines. Clin Gastroenterol Hepatol. 2023 Mar;21(3):581-603.e33. doi: 10.1016/j.cgh.2022.12.006. Epub 2022 Dec 20. — View Citation

Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019 Dec;16(12):713-732. doi: 10.1038/s41575-019-0189-8. Epub 2019 Aug 27. — View Citation

Patel SG, Karlitz JJ, Yen T, Lieu CH, Boland CR. The rising tide of early-onset colorectal cancer: a comprehensive review of epidemiology, clinical features, biology, risk factors, prevention, and early detection. Lancet Gastroenterol Hepatol. 2022 Mar;7(3):262-274. doi: 10.1016/S2468-1253(21)00426-X. Epub 2022 Jan 26. — View Citation

Rogers CR, Brooks E, Curtin K, De Vera MA, Qeadan F, Rogers TN, Petersen E, Gallagher P, Pesmen C, Johnson W, Henley C, Hickman W, Newcomb E, Korous KM, Handley MA. Protocol for #iBeatCRC: a community-based intervention to increase early-onset colorectal cancer awareness using a sequential explanatory mixed-methods approach. BMJ Open. 2021 Dec 3;11(12):e048959. doi: 10.1136/bmjopen-2021-048959. — View Citation

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209-249. doi: 10.3322/caac.21660. Epub 2021 Feb 4. — View Citation

Syed H, Sommovilla J, Burke CA, McGee S, Macaron C, Heald B, Lyu R, Schmit SL, Nair K, Kamath S, Krishnamurthi S, Khorana AA, Liska D. Referral, Uptake, and Outcome of Genetic Counseling and Testing in Patients With Early-Onset Colorectal Cancer. J Natl Compr Canc Netw. 2023 Nov;21(11):1156-1163.e5. doi: 10.6004/jnccn.2023.7057. — View Citation

Ullah F, Pillai AB, Omar N, Dima D, Harichand S. Early-Onset Colorectal Cancer: Current Insights. Cancers (Basel). 2023 Jun 15;15(12):3202. doi: 10.3390/cancers15123202. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity	True Positive Rate: the probability of a positive test result, conditioned on the individual truly being positive	Through study completion, an average of 1 year
Secondary	Specificity	True Negative Rate: the probability of a negative test result, conditioned on the individual truly being negative	Through study completion, an average of 1 year
Secondary	Proportion of correct predictions (true positives and true negatives) among the total cases (i.e., accuracy)	A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined	Through study completion, an average of 1 year