Early Detection of Advanced Adenomas and Colorectal Cancer (AACRC)

April 1, 2024 updated by: City of Hope Medical Center

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Estimated)

2000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Dalian, China
        • Recruiting
        • The First Affiliated Hospital of Dalian Medical University
        • Contact:
          • Jing Zhang
        • Sub-Investigator:
          • Caiming Xu
        • Sub-Investigator:
          • Jing Zhang
  • Italy
      • Milan, Italy
        • Recruiting
        • IRCCS San Raffaele
        • Sub-Investigator:
          • Alessandro Mannucci
        • Contact:
        • Sub-Investigator:
          • Giulia Martina Cavestro
  • Japan
      • Mie, Japan
        • Recruiting
        • Mie University
        • Contact:
          • Yuji Toiyama
        • Sub-Investigator:
          • Yuji Toiyama
        • Sub-Investigator:
          • Yoshinaga Okugawa
        • Sub-Investigator:
          • Tadanobu Shimura
  • Spain
      • Barcelona, Spain
        • Recruiting
        • Barcelona University
        • Contact:
        • Sub-Investigator:
          • Francesc Balaguer
        • Sub-Investigator:
          • Miguel Pera
        • Sub-Investigator:
          • Lorena Moreno
        • Sub-Investigator:
          • Luis Bujanda
  • United States
    • California
      • Monrovia, California, United States, 91016
        • Recruiting
        • City of Hope Medical Center
        • Contact:
        • Principal Investigator:
          • Ajay Goel, PhD
        • Sub-Investigator:
          • Alessandro Mannucci
        • Sub-Investigator:
          • Caiming Xu
        • Sub-Investigator:
          • James Lin
        • Sub-Investigator:
          • Gregory Idos
        • Sub-Investigator:
          • Trilokesh Kadambi
      • San Diego, California, United States, 92093
        • Recruiting
        • University of California San Diego
        • Contact:
          • C Richard Boland, MD, PhD
        • Sub-Investigator:
          • C Richard Boland, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

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

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Non-disease controls (Discovery cohort)
Individuals who underwent colonoscopy and were found not to have any adenomas or cancer.
Low-risk Adenoma (Discovery cohort)

Individuals who underwent colonoscopy and were found to only have low-risk adenomas, defined as all of the following:

  • 1 or 2 adenomas at most.
  • All adenomas have low-grade dysplasia at most.
  • All adenomas are <10 mm in diameter.
  • All adenomas are tubular
Advanced Adenoma (Discovery cohort)

Individuals who underwent colonoscopy and were found to have high-risk adenomas, defined as one or more of the following:

  • 3 or more adenomas.
  • One or more adenomas have high-grade dysplasia.
  • One or more adenomas are >10 mm in diameter.
  • One or more adenomas are villous
Colorectal Cancer (Discovery cohort)
Individuals who underwent colonoscopy and were found to have colorectal cancer.
Non-disease controls (Training cohort)
Individuals who underwent colonoscopy and were found not to have any adenomas or cancer.
Diagnostic test: DENEB
A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.
Other Names:
  • DENEB (DEtection of colorectal NEoplasias in Blood)
Low-risk Adenoma (Training cohort)

Individuals who underwent colonoscopy and were found to only have low-risk adenomas, defined as:

  • 1 or 2 adenomas at most.
  • All adenomas have low-grade dysplasia at most.
  • All adenomas are <10 mm in diameter.
  • All adenomas are tubular
Diagnostic test: DENEB
A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.
Other Names:
  • DENEB (DEtection of colorectal NEoplasias in Blood)
Advanced Adenoma (Training cohort)

Individuals who underwent colonoscopy and were found to have high-risk adenomas, defined as one or more of the following:

  • 3 or more adenomas.
  • One or more adenomas have high-grade dysplasia.
  • One or more adenomas are >10 mm in diameter.
  • One or more adenomas are villous
Diagnostic test: DENEB
A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.
Other Names:
  • DENEB (DEtection of colorectal NEoplasias in Blood)
Colorectal Cancer (Training cohort)
Individuals who underwent colonoscopy and were found to have colorectal cancer.
Diagnostic test: DENEB
A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.
Other Names:
  • DENEB (DEtection of colorectal NEoplasias in Blood)
Non-disease controls (Validation cohort)
Individuals who underwent colonoscopy and were found not to have any adenomas or cancer.
Diagnostic test: DENEB
A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.
Other Names:
  • DENEB (DEtection of colorectal NEoplasias in Blood)
Low-risk Adenoma (Validation cohort)

Individuals who underwent colonoscopy and were found to only have low-risk adenomas, defined as:

  • 1 or 2 adenomas at most.
  • All adenomas have low-grade dysplasia at most.
  • All adenomas are <10 mm in diameter.
  • All adenomas are tubular
Diagnostic test: DENEB
A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.
Other Names:
  • DENEB (DEtection of colorectal NEoplasias in Blood)
Advanced Adenoma (Validation cohort)

Individuals who underwent colonoscopy and were found to have high-risk adenomas, defined as one or more of the following:

  • 3 or more adenomas.
  • One or more adenomas have high-grade dysplasia.
  • One or more adenomas are >10 mm in diameter.
  • One or more adenomas are villous
Diagnostic test: DENEB
A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.
Other Names:
  • DENEB (DEtection of colorectal NEoplasias in Blood)
Colorectal Cancer (Validation cohort)
Individuals who underwent colonoscopy and were found to have colorectal cancer.
Diagnostic test: DENEB
A panel of circulating microRNA, whose expression level is tested in cell-free and exosome-derived samples.
Other Names:
  • DENEB (DEtection of colorectal NEoplasias in Blood)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sensitivity
Time Frame: Through study completion, an average of 1 year
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Specificity
Time Frame: Through study completion, an average of 1 year
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
Proportion of correct predictions (true positives and true negatives) among the total number of cases (i.e., accuracy)
Time Frame: Through study completion, an average of 1 year
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Investigators

  • Principal Investigator: Ajay Goel, PhD, City of Hope Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2020

Primary Completion (Estimated)

December 15, 2025

Study Completion (Estimated)

December 15, 2025

Study Registration Dates

First Submitted

March 26, 2024

First Submitted That Met QC Criteria

April 1, 2024

First Posted (Actual)

April 2, 2024

Study Record Updates

Last Update Posted (Actual)

April 2, 2024

Last Update Submitted That Met QC Criteria

April 1, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23228/AACRC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Data collected for the study will be made available to others, including de-identified participant data, at publication, via a signed data access agreement and at the discretion of the investigators' approval of the proposed use of such data.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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