NCT06342440

Early Detection of Advanced Adenomas and Colorectal Cancer

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

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 2,000 (estimated)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

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

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	DENEB	A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.

Timeline

• Start date: 2020-03-15
• Primary completion: 2026-06-18
• Completion: 2026-06-18
• First posted: 2024-04-02
• Last updated: 2025-06-17

Locations

6 sites across 5 countries: United States, China, Italy, Japan, Spain