Earlier Detection and Optimization of Treatment and Prognosis for Patients With Early-onset Colorectal Cancer

Recruiting

• Conditions: Early-onset Colorectal Cancer

• Registration Number: NCT06568679
• Lead Sponsor: The Netherlands Cancer Institute

Brief Summary

The study aims to collect high quality clinical data on lifestyle and patient biomaterials prior to start or during / after treatment of early-onset colorectal cancer (EOCRC) and to inform on treatment and survival outcomes of EOCRC patients.

Detailed Description

The current study will be complementary to COMPRAYA, a prospective cohort study focused on risk factors of impaired medical and psychosocial outcomes of adolescents and young adults with cancer (AYA) and to GENAYA, focused on genetic testing of AYA. The collected data and materials will be essential for an in-depth analysis of the epidemiology, exposomes and pathophysiology of EOCRC and compare this with average-onset CRC (AOCRC) and healthy controls. These data will facilitate multiomics studies and the identification of high-risk profiles and blood- and/or stool-based biomarkers, which in turn will enable the development of prevention and early detection strategies to ultimately improve prognosis and the prevalence, risk factors and mechanisms of impaired health outcomes (short- and long-term medical and psychosocial effects and late effects) over time among EOCRC patients wil be examined.

Study Timeline

• Study First Submitted: 2024-08-16
• Study First Submitted QC: 2024-08-20
• Study First Posted: 2024-08-23
• Study Start: 2025-01-27
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-21
• Primary Completion: 2037-12-01
• Study Completion: 2038-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Patients with locoregional or metastatic colorectal cancer (CRC)
• Histologically proven CRC
• Age 18 - 49 years at time of first CRC diagnosis
• Able to understand the informed consent form
• Provide written informed consent.

Exclusion Criteria

• Mentally incompetent patients based on the opinion of treating physician
• Inability to understand the Dutch language

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Exploratory data analysis through a multiomics approach describing tumor biology and pathogenesis of patients with EOCRC	Change from baseline throughout follow-up of 10 years	Associations between exposome (lifestyle factors and microbiome composition), genomics and transcriptomics and EOCRC will be determined by multivariate analysis. Multivariate tests will be applied to account for the complexity of the data and the multitude of variables involved, this will include multiple regression analysis, logistic regression analysis, and analysis of variance (ANOVA). These tests will allow us to identify and quantify the correlation between the factors and better understand the underlying mechanisms of EOCRC.

Secondary Outcome Measures

Name	Time	Method
To compare stage-specific treatment and survival outcomes of patients with EOCRC with those of AOCRC (≥ 50 years)	Change from baseline throughout follow-up of 10 years	Treatment and survival outcomes (progression free survival and/or recurrence free survival and overall survival) will be estimated with Kaplan-Meier curves and medians with 95% confidence intervals (CIs) will be presented and will be compared to survival outcomes of AOCRC (≥ 50 years) of a matched control group from the NCR.
High risk profiles	Change from baseline throughout follow-up of 10 years	By a multiomics approach associations between exposomes (lifestyle, microbiome), (epi-)genomics and transcriptomics in EOCRC development and tumor phenotype will be analysed to assign high risk profiles to provide rationale for the selection of target populations that should be offered CRC screening at an earlier age.
Survival	Change from baseline throughout follow-up of 10 years	Linkage will done with the Personal Records Database (BRP) to have information on survival status
Second tumor	Change from baseline throughout follow-up of 10 years	Linkage to the Netherlands Cancer Registry (NCR) and nationwide National Pathology Database (PALGA) to asses second malignancies.
Germline variants will be analysed in the carcinogenesis of EOCRC	Change from baseline throughout follow-up of 10 years	The frequencies of germline variants that are known risk factors to cancer development will be determined. Generally, hereditary colorectal cancers will be analyzed both together with and separately from sporadic colorectal cancers. The contribution of germline variants to carcinogenesis via mutational signatures will be determined, where possible, using linear mixed models.
Psychological distress	Change from baseline throughout follow-up of 10 years	Psychological distress will be assessed at each time point with the Hospital Anxiety and Depression Scale (HADS), with seven items each for assessing symptoms of anxiety and depression
Geno-phenotype associations	Change from baseline throughout follow-up of 10 years	Geno-phenotype associations of patients will be analysed in-depth based on whole genome sequencing (WGS), histopathological features and survival outcomes.

Trial Locations

Locations (1)

Netherlands Cancer Institute; 🇳🇱 Amsterdam, Noord-Holland, Netherlands