Colorectal Adenocarcinoma, Colorectal Cancer, Colorectal Cancer Recurrent, Colorectal Cancer Stage II, Colorectal Cancer Stage III
Conditions
Keywords
Recurrence-free Survival (RFS), Overall Survival (OS), Methylation, DNA methylation, carcinoembryonic antigen (CEA)
Brief summary
This study will develop an assay to predict disease recurrence in patients with stage II/III CRC after receiving adjuvant chemotherapy, using genome-wide DNA methylation.
Detailed description
Adjuvant chemotherapy (ACT) is the standard clinical care for patients with stage III or high-risk stage II colorectal cancer (CRC) after curative-intent resection. Nonetheless, more than 30% of patients experience CRC recurrence. Accurate prediction of recurrence risk in stage II/III CRC patients who undergo ACT is crucial for determining the necessity and duration of ACT, as well as for tailoring novel treatment strategies for these patients. This study will comprise three phases 1. A systematic and comprehensive CpG methylation-based epigenetic biomarker discovery phase to identify the differentially methylated CpG sites associated with recurrence-free survival (RFS) \< 5 years and \> 5 years. In this phase, LASSO-based machine learning algorithms will be used to optimize the biomarker candidates. 2. A tissue-based clinical assay development phase by quantitative pyrosequencing 3. An independent validation phase. At completion, this study will validate a tissue-based assay to predict the development of recurrence after the completion of chemotherapy in patients with stage III and II CRC
Interventions
OTHERCENSURE
A panel of CpG sites, whose methylation level is tested in macro-dissected formalin-fixed and paraffin-embedded (FFPE) samples derived from the primary tumor.
Sponsors
City of Hope Medical Center
Study design
Observational model
CASE_CONTROL
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Stage II (high-risk) or III colorectal cancer (TNM classification, 8th edition). * Received standard diagnostic, staging, and therapeutic procedures as per local guidelines * Received stage-specific curative-intent resection followed by adjuvant chemotherapy. * Confirmed cancer-free survivorship confirmed at the time of study inclusion.
Exclusion criteria
* Lack of written informed consent. * Development of recurrence in the first 6 months following adjuvant chemotherapy completion. * Hereditary colorectal cancer syndromes (identified through genetic testing) * Inflammatory bowel diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recurrence-Free Survival | Up to 120 months | Time from treatment completion to development of recurrence (or death) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Up to 120 months | Time from treatment completion to death from any cause |
Countries
China, Spain, United States
Contacts
CONTACTAjay Goel, PhD
PRINCIPAL_INVESTIGATORAjay Goel, PhD
City of Hope Medical Center
Outcome results
None listed