Clinical trial NCT06342440: Early Detection of Advanced Adenomas and Colorectal Cancer
Official title: A Liquid Biopsy Assay For The Non-Invasive Early Detection of Advanced Adenomas and Colorectal Cancer
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Colorectal Cancer
Colorectal Neoplasms
Colorectal Polyp
Colorectal Adenocarcinoma
Colorectal Disorders
Colorectal Dysplasia
Colorectal Cancer Stage I
Colorectal Cancer Stage II
Colorectal Cancer Stage III
Colorectal Cancer Stage IV
Colorectal Neoplasms Malignant
Colorectal Serrated Adenocarcinoma
Colorectal Adenoma With Severe Dysplasia
Colorectal Adenoma With Mild Dysplasia
Colorectal Adenoma With Moderate Dysplasia
Colorectal Adenoma and Carcinoma 1
Colorectal Adenomatous Polyp
Colorectal Adenocarcinoma Metastatic in the Liver
Keywords: Early detection
Micro RNA
miRNA
Liquid biopsy
Machine learning
Artificial Intelligence
Incidence
Polypectomy
Screening
Surveillance
Exosome
Vascicles
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
First posted: 2024-04-02
Enrollment: 2000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Three independent cohorts of individuals who belong to one of the following four

* Negative colonoscopy findings
* Low-risk adenomas (at most)
* Advanced adenomas (at most)
* Colorectal cancer

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Sensitivity
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: Specificity
timeFrame: Through study completion, an average of 1 year
measure: Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e., accuracy)
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Monrovia
country: United States
facility: City of Hope Medical Center
state: California
city: San Diego
country: United States
facility: University of California San Diego
state: California
city: Dalian
country: China
facility: The First Affiliated Hospital of Dalian Medical University
city: Milan
country: Italy
facility: IRCCS San Raffaele
city: Mie
country: Japan
facility: Mie University
city: Barcelona
country: Spain
facility: Barcelona University
Study officials:
affiliation: City of Hope Medical Center
name: Ajay Goel, PhD
role: PRINCIPAL_INVESTIGATOR
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