Early-Onset Colorectal Cancer: An Observational Retrospective and Prospective Multicenter Study (HEBE)

Early-Onset Colorectal Cancer: An Observational Retrospective and Prospective Multicenter Study - (The HEBE Study)

Observational, retrospective and prospective multicentric Italian study of patients diagnosed with colorectal cancer between age 18-40, aiming at underpinning the biology of vEO-CRC, including colibactin as well as a broader proteo-genomic characterization, to identify potential new therapeutic targets specifically directed to this peculiar subset of patients.

Study Overview

• Status: Recruiting
• Conditions: Colo-rectal Cancer
• Intervention / Treatment: Biological: BIOLOGICAL STUDY aiming at describing clinicophatological features of EO-CRC vs SO-CRC

Detailed Description

Clinicopathological features, and survival data will be pseudo-anonymized and collected through a dedicated ReDCap database by each participating center.

Colibactin assessment - FFPE samples will be stratified between colibactin-positive and negative ones using endpoint PCR. We will use primers flanking multiple regions of the colibactin genomic island (in particular, CLBO on the 5'-end, CLBI in the middle and CLBB on the 3'-end), since a fully intact sequence is required to produce a functional toxin 13. Amplicons will be around 100bp in length (150bp maximum) based on fragment size of plasma-derived DNA, and PCRs will be performed following a touchdown protocol. In a second approach, quantitative polymerase chain reaction (qPCR) will be performed to provide more quantitative correlation between colibactin and clinically relevant patient outcomes. We will amplify amplicons on the same regions used for the endpoint PCRs described above, and we will use primers flanking bacterial 16S sequence to estimate bacterial DNA content in plasma.

Proteogenomic assessment - An initial subset of 50 vEO-CRC and 50 SO-CRC will undergoing full proteomic assessment by mass spectrometry and whole genome sequencing (WGS). Potential findings on this initial subset of patients will be then validated by immunohistochemistry, polymerase chain reaction (PCR), Next Generation Sequencing (NGS) or In-situ ibridization (ISH). These translational analyses will be performed at Grande Ospedale Metropolitano Niguarda, University of Turin, Istituto Nazionale di Genetica Medica (INGM) in Milan andIFOM-ETS which will be the preclinical partners of this project.

Thanks to the collaboration with Azienda Territoriale Sanitaria (ATS)of the Metropolitan Area of Milan we will have access to epidemiological data regarding the real incidence of vEO CRC over the time.

Liquid biopsy validation of proteogenomic findings from solid tissue - If available, 4 ml of plasma retrospectively collected through liquid biopsy and stored in participating centers will be queried to assess whether genomic or proteomic alterations can be identified in blood.

Primary objective:

1. to analyze clinicopathological features of a cohort of sporadic vEO-CRC (n=300), compared to an equal cohort of standard-onset (SO-CRC) patients diagnosed at 60 years or later;
2. to analyze overall survival and response to standard-of-care treatments of a cohort of sporadic vEO-CRC (n=300), compared to an equal cohort of standard-onset (SO-CRC) patients diagnosed at 60 years or later;

Secondary objective :

1. to assess the prevalence of colibactin in a cohort of sporadic vEO-CRC (n=300), compared to an equal cohort of standard-onset (SO-CRC) patients diagnosed at 60 years or later;
2. to perform a proteo-genomic characterization of a cohort of sporadic vEO-CRC (n=300), compared to an equal cohort of standard-onset (SO-CRC) patients diagnosed at 60 years or later.

Exploratory objective :

1. to assess if colibactin and potential proteo-genomic features of vEO-CRC can be also captured on plasma through liquid biopsy.

• Study Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Salvatore Siena, MD; Phone Number: 3695 +39 02 6444; Email: salvatore.siena@ospedaleniguarda.it
• Study Contact Backup: Name: Andrea Sartore Bianchi, MD; Phone Number: 3695 +39 02 6444; Email: andrea.sartorebianchi@ospedaleniguarda.it

Study Locations

• Italy
  • Milano, Italy, 20162
    • Recruiting
    • ASST Grande Ospedale Metropolitano Niguarda
    • Contact: Salvatore Siena, MD; Phone Number: 3695 +39 02 6444; Email: salvatore.siena@ospedaleniguarda.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Colorectal cancer pts

Description

1. Patients with diagnosis of colorectal cancer (vEO-CRC: 18-40 years of age), or SO-CRC diagnosed later than age 60;
2. Informed consent signature from alivepatient;
3. Availability of formalin-fixed paraffin embedded (FFPE) tumor samples (5 FFPE 4uM thick slides and 10 FFPE 10 uM thick slides) and/or fresh tumor tissue retrieved from a biopsy or surgical procedure performed as per clinical standard of care.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Early-Onset(EO) Colorectal Cancer (CRC); EO-CRC: 18-40 years of age at diagnosis	Biological: BIOLOGICAL STUDY aiming at describing clinicophatological features of EO-CRC vs SO-CRC; Description of clinicophatological features of EO-CRC vs SO-CRC
Standard onset (SO) Colorectal Cancer; SO-CRC diagnosed later than age 60	Biological: BIOLOGICAL STUDY aiming at describing clinicophatological features of EO-CRC vs SO-CRC; Description of clinicophatological features of EO-CRC vs SO-CRC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinicopathological features description	Primaryto analyze clinicopathological features of a cohort of sporadic vEO-CRC (n=300), compared to an equal cohort of standard-onset (SO-CRC) patients diagnosed at 60 years or later;	Apr 2024- Dec2026
overall survival and response to standard-of-care treatments analisys	to analyze overall survival and response to standard-of-care treatments of a cohort of sporadic vEO-CRC (n=300), compared to an equal cohort of standard-onset (SO-CRC) patients diagnosed at 60 years or later;	Apr 2024- Dec2026

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prevalence of colibactin assessment	to assess the prevalence of colibactin in a cohort of sporadic vEO-CRC (n=300), compared to an equal cohort of standard-onset (SO-CRC) patients diagnosed at 60 years or later;	Apr 2024- Dec2026
perform a proteo-genomic characterization	to perform a proteo-genomic characterization of a cohort of sporadic vEO-CRC (n=300), compared to an equal cohort of standard-onset (SO-CRC) patients diagnosed at 60 years or later.	Apr 2024- Dec2026

Collaborators and Investigators

• Sponsor: Niguarda Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: May 2, 2025
• First Submitted That Met QC Criteria: May 2, 2025
• First Posted (Actual): May 11, 2025

Study Record Updates

• Last Update Posted (Actual): May 11, 2025
• Last Update Submitted That Met QC Criteria: May 2, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Early-Onset Colorectal Cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 4528

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No