Early Detection of Advanced Adenomas and Colorectal Cancer

Colorectal Cancer Clinical Trial

— AACRC  

Official title:

A Liquid Biopsy Assay For The Non-Invasive Early Detection of Advanced Adenomas and Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06342440
• Other study ID #: 23228/AACRC
• Status: Recruiting
• Start date: March 15, 2020
• Est. completion date: December 15, 2025

Study information

• Verified date: June 2024
• Source: City of Hope Medical Center
• Contact: Ajay Goel, PhD
• Phone: 6262183452
• Email: AJGOEL[@]COH.ORG
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study aims to develop a highly sensitive, specific, and cost-effective blood assay for early detection of colorectal adenomas and cancer, using advanced machine learning and state-of-the-art biological analyses.

Description:

Colorectal cancer (CRC) is a significant global health concern, ranking third in diagnosis and second in mortality. Despite being potentially preventable, it remains a leading cause of cancer-related deaths. Traditional screening methods like fecal immunochemical testing (FIT) have shown benefits in reducing late-stage diagnoses but have not effectively prevented CRC incidence. This is because tests like FIT can effectively detect the cancers, but not the precursor lesions, called adenomas. On the other hand, endoscopy-first approaches offer higher sensitivity for such adenomas and, therefore, lower the risk of developing CRC but face challenges such as invasiveness, cost, and patient compliance.

Non-invasive tests are more appealing to patients than invasive tests and can increase participation rates. Biomarker studies have shown promise, but existing tests lack sensitivity for early-stage CRC and advanced adenomas (AAs). This is likely because they assume the same analyte can detect both CRC and AAs, which may not be accurate due to differences in analyte release and the biological changes that occur during the adenoma-carcinoma sequence.

This study proposes developing an innovative liquid biopsy test tailored for AAs and CRC to address this. An ideal screening test should be minimally invasive, highly sensitive, and cost-effective. This test would optimize patient compliance and resource allocation by detecting both conditions from a single blood draw. More specifically, circulating microRNA (miRNA) analysis shows promise: tests based on cell-free microRNA (cf-miRNA) have demonstrated high sensitivity, while those based on exosome-derived microRNA (exo-miRNA) offer high specificity. Therefore, combining both analytes in a single test could maximize sensitivity and specificity.

This study will develop a non-invasive blood test for AA and CRC in four phases:

1. Genome-wide profiling of cf-miRNA and exo-miRNA and selecting the best candidates for biomarker panels.

2. Utilizing machine learning to identify promising candidates and train algorithms for detecting AAs and CRC separately, based on results from quantitative polymerase chain reaction (qPCR) analysis.

3. Combining these algorithms to create detection signatures for both conditions.

4. Independently validating these signatures using diverse cohorts to ensure broad applicability and compare the effectiveness of the blood assay to standard care through retrospective and prospective studies.

This study aims to develop a highly sensitive, specific, and cost-effective liquid biopsy for early detection of AAs and CRC. Success could transform clinical practice by preventing CRC through early detection of pre-malignant lesions. Innovations include incorporating pre-malignant lesions into screening and combining cf-miRNA and exo-miRNA biomarkers for accuracy. This approach could reduce CRC mortality and incidence and pave the way for new clinical trials.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: December 15, 2025
• Est. primary completion date: December 15, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• All individuals included in the study need to have had a colonoscopy at the time of blood sampling.

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

• Received standard pathological and endoscopic diagnosis and assessment for cohort assignment.

Exclusion Criteria:

• Hereditary colorectal cancer syndromes (identified through genetic testing).

• Inflammatory bowel diseases.

• Lack of written informed consent.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenoma
• Adenomatous Polyps
• Colorectal Adenocarcinoma
• Colorectal Adenoma With Mild Dysplasia
• Colorectal Adenoma With Severe Dysplasia
• Colorectal Adenomatous Polyp
• Colorectal Cancer
• Colorectal Cancer Stage I
• Colorectal Cancer Stage II
• Colorectal Cancer Stage III
• Colorectal Cancer Stage IV
• Colorectal Disorders
• Colorectal Neoplasms
• Colorectal Neoplasms Malignant
• Colorectal Polyp
• Hyperplasia
• Neoplasms
• Polyps

Intervention

Diagnostic Test:
• DENEB
A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.

Locations

Country	Name	City	State
China	The First Affiliated Hospital of Dalian Medical University	Dalian
Italy	IRCCS San Raffaele	Milan
Japan	Mie University	Mie
Spain	Barcelona University	Barcelona
United States	City of Hope Medical Center	Monrovia	California
United States	University of California San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
City of Hope Medical Center

Countries where clinical trial is conducted

United States,  China,  Italy,  Japan,  Spain, 

References & Publications (29)

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* Note: There are 29 references in all — Click here to view all references

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 number of 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