Early Onset Colorectal Cancer Detection
- Conditions
- Colorectal CancerColorectal NeoplasmsColorectal AdenocarcinomaColorectal Cancer Stage IColorectal Cancer Stage IVColorectal Cancer Stage IIColorectal Neoplasms MalignantColorectal Cancer Stage III
- Interventions
- Diagnostic Test: ENCODE
- Registration Number
- NCT06342401
- Lead Sponsor
- City of Hope Medical Center
- Brief 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)
- Detailed 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 & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 400
- 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)
- Hereditary colorectal cancer syndromes (identified through genetic testing)
- Inflammatory bowel diseases
- Lack of written informed consent
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Early onset colorectal cancer (Training cohort) ENCODE Colorectal cancer diagnosed before the age of 50 Non-disease controls (Training cohort) ENCODE Individuals free from colorectal cancer, younger than 50 years of age Early onset colorectal cancer (Validation cohort) ENCODE Colorectal cancer diagnosed before the age of 50 Non-disease controls (Validation cohort) ENCODE Individuals free from colorectal cancer, younger than 50 years of age
- Primary Outcome Measures
Name Time Method Sensitivity 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
- Secondary Outcome Measures
Name Time Method Specificity 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
Proportion of correct predictions (true positives and true negatives) among the total cases (i.e., accuracy) 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
Trial Locations
- Locations (13)
Colorectal Surgery, Vall d'Hebron University Hospital, Universitat Autonoma de Barcelona UAB
🇪🇸Barcelona, Spain
Surgery Department, Hospital del Mar, Barcelona, Spain
🇪🇸Barcelona, Spain
University of Salamanca-SACYL-CSIC, Salamanca, Spain
🇪🇸Salamanca, Spain
City of Hope Medical Center
🇺🇸Duarte, California, United States
IRCCS San Raffaele
🇮🇹Milan, Italy
Kawasaki University
🇯🇵Kawasaki, Japan
Mie University
🇯🇵Mie, Japan
National Cancer Center Hospital
🇯🇵Tokyo, Japan
Tokyo Medical and Dental University
🇯🇵Tokyo, Japan
Yamagata University
🇯🇵Yamagata, Japan
Barcelona University
🇪🇸Barcelona, Spain
University of La Laguna
🇪🇸La Laguna, Spain
Salamanca Biomedical Research Institute
🇪🇸Madrid, Spain