CRC (Colorectal Cancer)EpiCORENCT07224815

cfDNA 5mC/5hmC Biomarkers to Predict Chemotherapy Response in Metastatic Colorectal Cancer

An observational study of CRC (Colorectal Cancer), run by City of Hope Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Trial summary

The EpiCORE study aims to identify cfDNA-based epigenetic markers predictive of response to first-line chemotherapy (FOLFOX or FOLFIRI) in metastatic colorectal cancer (mCRC). By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to establish a non-invasive biomarker… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: CRC (Colorectal Cancer)
What is being tested?: cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase) and EpiCORE Assay (Targeted Sequencing / qPCR Validation)
How many people: 600 participants
Where: 1 siteUnited States
Study dates: 21 Jun 2024to 18 Jun 2028
Phase: Observational
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: Patients diagnosed with Stage IV colorectal adenocarcinoma who received first-line FOLFOX or FOLFIRI chemotherapy and have available pre-treatment serum or plasma samples for cfDNA analysis.

Who may be able to join

Histologically confirmed metastatic colorectal adenocarcinoma (mCRC).
Received first-line chemotherapy (FOLFOX or FOLFIRI).
Availability of pre-treatment serum or plasma samples for cfDNA 5mC/5hmC analysis.
Documented radiologic or clinical response evaluation (RECIST 1.1 or PFS-based).
RAS/BRAF mutation status available.

Who cannot join

Inadequate cfDNA yield or poor DNA quality.
Non-adenocarcinoma histology.
Active inflammatory or autoimmune disease that may alter cfDNA methylation.
Concomitant malignancy requiring systemic therapy.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ajay Goel, PhD contact

6263598111

ajgoel@coh.org

United States1 site, 1 recruiting

City of Hope Medical Center
Duarte, California, 91010
Ajay Goel, PhD, 626-218-3452, ajgoel@coh.org
Recruiting

Other trials in United States

About this study

Official title: Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Predict Chemotherapy Efficacy in Metastatic Colorectal Cancer

The EpiCORE study aims to identify cfDNA-based epigenetic markers predictive of response to first-line chemotherapy (FOLFOX or FOLFIRI) in metastatic colorectal cancer (mCRC).

By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to establish a non-invasive biomarker panel capable of distinguishing responders from non-responders.

Read the detailed description

Despite the introduction of multi-agent chemotherapy regimens such as FOLFOX (5-FU, leucovorin, oxaliplatin) and FOLFIRI (5-FU, leucovorin, irinotecan), treatment outcomes in metastatic colorectal cancer (mCRC) remain highly variable.

Current predictive biomarkers, such as RAS/BRAF mutation or microsatellite instability, fail to accurately forecast response to cytotoxic chemotherapy.

Emerging evidence suggests that cfDNA methylation (5mC) and hydroxymethylation (5hmC) patterns reflect tumor biology and drug sensitivity, offering a promising avenue for precision chemotherapy.

The EpiCORE study integrates genome-wide 5mC/5hmC sequencing and targeted validation assays to identify and confirm epigenetic determinants of chemotherapy efficacy.

Discovery phase: Genome-wide 5mC/5hmC profiling of cfDNA from patients treated with first-line FOLFOX or FOLFIRI to identify candidate regions associated with treatment response.

Training phase: Targeted sequencing and model construction based on candidate loci.

Validation phase: qPCR-based testing to confirm predictive accuracy of the finalized EpiCORE panel.

This study aims to establish a robust cfDNA biomarker framework for predicting and monitoring chemotherapy response in mCRC, contributing to individualized therapeutic decision-making.

Conditions: CRC (Colorectal Cancer)
Being tested: cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase), EpiCORE Assay (Targeted Sequencing / qPCR Validation)
Keywords: CRC, Colorectal cancer, 5mC, 5hmC, RAS/BRAF mutation, FOLFOX, FOLFIRI, hydroxymethylation
Medical subject headings: Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase)Diagnostic test
Genome-wide profiling of cfDNA methylation and hydroxymethylation from pre-treatment plasma to identify molecular determinants associated with chemotherapy efficacy (PFS ≥ 12M vs < 12M).
EpiCORE Assay (Targeted Sequencing / qPCR Validation)Diagnostic test
Targeted validation of cfDNA 5mC/5hmC markers from discovery phase using sequencing and qPCR to build and validate a predictive model for first-line chemotherapy response.

Study groups in NCT07224815
Study group	Role	What they receive
Discovery Cohort - PFS ≥ 12 Months (Responder)		Patients with mCRC who achieved progression-free survival ≥ 12 months after first-line chemotherapy (FOLFOX or FOLFIRI). cfDNA 5mC/5hmC sequencing performed to identify epigenetic determinants of durable response. Receives: Diagnostic Test: cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase)
Discovery Cohort - PFS < 12 Months (Non-Responder)		Patients with progression-free survival < 12 months after first-line chemotherapy. Compared with responders to identify epigenetic features associated with resistance. Receives: Diagnostic Test: cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase)
Training Cohort - PFS ≥ 12 Months (Responder)		Independent mCRC cohort with long PFS (≥12M). Targeted sequencing (EpiCORE assay) to refine predictive markers. Receives: Diagnostic Test: EpiCORE Assay (Targeted Sequencing / qPCR Validation)
Training Cohort - PFS < 12 Months (Non-Responder)		Independent mCRC cohort with short PFS (<12M). Targeted sequencing to validate resistance-associated markers. Receives: Diagnostic Test: EpiCORE Assay (Targeted Sequencing / qPCR Validation)
Validation Cohort - PFS ≥ 12 Months (Responder)		Independent validation cohort analyzed with qPCR-based EpiCORE assay to confirm biomarker predictive accuracy. Receives: Diagnostic Test: EpiCORE Assay (Targeted Sequencing / qPCR Validation)
Validation Cohort - PFS < 12 Months (Non-Responder)		Independent validation cohort with poor PFS analyzed to assess specificity and model performance. Receives: Diagnostic Test: EpiCORE Assay (Targeted Sequencing / qPCR Validation)

What is being measured

The primary outcome is the main question the study is designed to answer.

Progression-Free Survival (PFS)
Progression-free survival (PFS) is defined as the time from initiation of first-line chemotherapy (FOLFOX or FOLFIRI) to the date of documented disease progression or death from any cause, whichever occurs first.
The primary objective of the EpiCORE study is to evaluate whether cfDNA 5mC/5hmC-based biomarker profiles (EpiCORE panel) are associated with differences in PFS among patients with metastatic colorectal cancer (mCRC).
Measured: Up to 36 months from initiation of first-line chemotherapy

Secondary outcomes (1)

Overall Survival (OS):
Time from chemotherapy initiation to death from any cause
Measured: Up to 60 months from initiation of first-line chemotherapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

21 Jun 202418 Jun 2028

First posted5 Nov 2025
Study start21 Jun 2024
Primary completion18 Jun 2028 (estimated)
Study completion18 Jun 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (17)Papers the sponsor has linked to this study.
Other trials for CRC (Colorectal Cancer)Studies of the same condition, open and under way.
More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Case-control
Time perspective: Retrospective
Enrolment: 600 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07224815
Sponsor's protocol ID: 23228/EpiCORE
Acronym: EpiCORE
Status last verified: Jul 2026
First submitted: 3 Nov 2025
Last updated: 7 Jul 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: 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.

Publications

Nelson MA, Shetty S, Kulakodlu M, Harley C, Seal B. A comparison of mortality and costs associated with FOLFOX versus FOLFIRI in stage IV colorectal cancer. J Med Econ. 2011;14(2):179-86. doi: 10.3111/13696998.2011.556693. Epub 2011 Feb 14.
PubMed 21319948
Bond MJG, Bolhuis K, Loosveld OJL, de Groot JWB, Droogendijk H, Helgason HH, Hendriks MP, Klaase JM, Kazemier G, Liem MSL, Rijken AM, Verhoef C, de Wilt JHW, de Jong KP, Gerhards MF, van Amerongen MJ, Engelbrecht MRW, van Lienden KP, Molenaar IQ, de Valk B, Haberkorn BCM, Kerver ED, Erdkamp F, van Alphen RJ, Mathijssen-van Stein D, Komurcu A, Lopez-Yurda M, Swijnenburg RJ, Punt CJA; Dutch Colorectal Cancer Study Group. First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group. Lancet Oncol. 2023 Jul;24(7):757-771. doi: 10.1016/S1470-2045(23)00219-X. Epub 2023 Jun 14.
PubMed 37329889
Bond MJG, Bolhuis K, Loosveld OJL, de Groot JWB, Droogendijk H, Helgason HH, Hendriks MP, Klaase JM, Kazemier G, Liem MSL, Rijken AM, Verhoef C, de Wilt JHW, de Jong KP, Gerhards MF, van Amerongen MJ, Engelbrecht MRW, van Lienden KP, Hermans JJ, Molenaar IQ, Grunhagen DJ, de Valk B, Haberkorn BCM, Kerver ED, Erdkamp F, van Alphen RJ, Mathijssen-van Stein D, Komurcu A, May AM, Swijnenburg RJ, Punt CJA; Dutch Colorectal Cancer Group. First-Line Systemic Treatment for Initially Unresectable Colorectal Liver Metastases: Post Hoc Analysis of the CAIRO5 Randomized Clinical Trial. JAMA Oncol. 2025 Jan 1;11(1):36-45. doi: 10.1001/jamaoncol.2024.5174.
PubMed 39570583
Neugut AI, Lin A, Raab GT, Hillyer GC, Keller D, O'Neil DS, Accordino MK, Kiran RP, Wright J, Hershman DL. FOLFOX and FOLFIRI Use in Stage IV Colon Cancer: Analysis of SEER-Medicare Data. Clin Colorectal Cancer. 2019 Jun;18(2):133-140. doi: 10.1016/j.clcc.2019.01.005. Epub 2019 Jan 31.
PubMed 30878317
Gibbons CE, Khan F. Dysphagia--a presenting symptom of forestier disease. J R Army Med Corps. 1996 Feb;142(1):32-3. doi: 10.1136/jramc-142-01-07.
PubMed 8667328
Guler GD, Ning Y, Coruh C, Mognol GP, Phillips T, Nabiyouni M, Hazen K, Scott A, Volkmuth W, Levy S. Plasma cell-free DNA hydroxymethylation profiling reveals anti-PD-1 treatment response and resistance biology in non-small cell lung cancer. J Immunother Cancer. 2024 Jan 11;12(1):e008028. doi: 10.1136/jitc-2023-008028.
PubMed 38212123
Ferrara R, Imbimbo M, Malouf R, Paget-Bailly S, Calais F, Marchal C, Westeel V. Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer. Cochrane Database Syst Rev. 2021 Apr 30;4(4):CD013257. doi: 10.1002/14651858.CD013257.pub3.
PubMed 33930176
Baldassarre G, L de la Serna I, Vallette FM. Death-ision: the link between cellular resilience and cancer resistance to treatments. Mol Cancer. 2025 May 15;24(1):144. doi: 10.1186/s12943-025-02339-1.
PubMed 40375296
Song D, Zhang Z, Zheng J, Zhang W, Cai J. 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation. Biomark Res. 2025 Mar 7;13(1):39. doi: 10.1186/s40364-025-00751-9.
PubMed 40055844
Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025 Jan-Feb;75(1):10-45. doi: 10.3322/caac.21871. Epub 2025 Jan 16.
PubMed 39817679
West-Szymanski DC, Zhang Z, Cui XL, Kowitwanich K, Gao L, Deng Z, Dougherty U, Williams C, Merkle S, Moore M, He C, Bissonnette M, Zhang W. Machine learning identifies cell-free DNA 5-hydroxymethylation biomarkers that detect occult colorectal cancer in PLCO Screening Trial subjects. bioRxiv [Preprint]. 2024 Feb 26:2024.02.25.581955. doi: 10.1101/2024.02.25.581955.
PubMed 38464122
West-Szymanski DC, Zhang Z, Cui XL, Kowitwanich K, Gao L, Deng Z, Dougherty U, Williams C, Merkle S, He C, Zhang W, Bissonnette M. 5-Hydroxymethylated Biomarkers in Cell-Free DNA Predict Occult Colorectal Cancer up to 36 Months Before Diagnosis in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. JCO Precis Oncol. 2024 Oct;8:e2400277. doi: 10.1200/PO.24.00277. Epub 2024 Oct 11.
PubMed 39393034
Zeng C, Stroup EK, Zhang Z, Chiu BC, Zhang W. Towards precision medicine: advances in 5-hydroxymethylcytosine cancer biomarker discovery in liquid biopsy. Cancer Commun (Lond). 2019 Mar 29;39(1):12. doi: 10.1186/s40880-019-0356-x.
PubMed 30922396
Xie YH, Chen YX, Fang JY. Comprehensive review of targeted therapy for colorectal cancer. Signal Transduct Target Ther. 2020 Mar 20;5(1):22. doi: 10.1038/s41392-020-0116-z.
PubMed 32296018
Tirendi S, Marengo B, Domenicotti C, Bassi AM, Almonti V, Vernazza S. Colorectal cancer and therapy response: a focus on the main mechanisms involved. Front Oncol. 2023 Jul 19;13:1208140. doi: 10.3389/fonc.2023.1208140. eCollection 2023.
PubMed 37538108

Interested in taking part?

Ajay Goel, PhD

6263598111

ajgoel@coh.org

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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All CRC (Colorectal Cancer) trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Predict Chemotherapy Efficacy in Metastatic Colorectal Cancer
ClinicalTrials.gov ID: NCT07224815
Acronym / sponsor ID: EpiCORE / 23228/EpiCORE
Conditions: CRC (Colorectal Cancer)
Keywords: CRC, Colorectal cancer, 5mC, 5hmC, RAS/BRAF mutation, FOLFOX, FOLFIRI, hydroxymethylation
Study type: Observational
Recruitment status: Recruiting
Enrolment: 600 participants (estimated)
Lead sponsor: City of Hope Medical CenterUniversity, hospital or other
Study start: 21 Jun 2024 (actual)
Primary completion: 18 Jun 2028 (estimated)
Study completion: 18 Jun 2028 (estimated)
First posted: 5 Nov 2025 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The EpiCORE study aims to identify cfDNA-based epigenetic markers predictive of response to first-line chemotherapy (FOLFOX or FOLFIRI) in metastatic colorectal cancer (mCRC).

Detailed description

Current predictive biomarkers, such as RAS/BRAF mutation or microsatellite instability, fail to accurately forecast response to cytotoxic chemotherapy.

Emerging evidence suggests that cfDNA methylation (5mC) and hydroxymethylation (5hmC) patterns reflect tumor biology and drug sensitivity, offering a promising avenue for precision chemotherapy.

The EpiCORE study integrates genome-wide 5mC/5hmC sequencing and targeted validation assays to identify and confirm epigenetic determinants of chemotherapy efficacy.

Discovery phase: Genome-wide 5mC/5hmC profiling of cfDNA from patients treated with first-line FOLFOX or FOLFIRI to identify candidate regions associated with treatment response.

Training phase: Targeted sequencing and model construction based on candidate loci.

Validation phase: qPCR-based testing to confirm predictive accuracy of the finalized EpiCORE panel.

This study aims to establish a robust cfDNA biomarker framework for predicting and monitoring chemotherapy response in mCRC, contributing to individualized therapeutic decision-making.

Study design

Observational model: Case-control
Time perspective: Retrospective
Number of arms: 6

Arm	Type	Receives
Discovery Cohort - PFS ≥ 12 Months (Responder)	–	Diagnostic Test: cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase)Patients with mCRC who achieved progression-free survival ≥ 12 months after first-line chemotherapy (FOLFOX or FOLFIRI). cfDNA 5mC/5hmC sequencing performed to identify epigenetic determinants of durable response.
Discovery Cohort - PFS < 12 Months (Non-Responder)	–	Diagnostic Test: cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase)Patients with progression-free survival < 12 months after first-line chemotherapy. Compared with responders to identify epigenetic features associated with resistance.
Training Cohort - PFS ≥ 12 Months (Responder)	–	Diagnostic Test: EpiCORE Assay (Targeted Sequencing / qPCR Validation)Independent mCRC cohort with long PFS (≥12M). Targeted sequencing (EpiCORE assay) to refine predictive markers.
Training Cohort - PFS < 12 Months (Non-Responder)	–	Diagnostic Test: EpiCORE Assay (Targeted Sequencing / qPCR Validation)Independent mCRC cohort with short PFS (<12M). Targeted sequencing to validate resistance-associated markers.
Validation Cohort - PFS ≥ 12 Months (Responder)	–	Diagnostic Test: EpiCORE Assay (Targeted Sequencing / qPCR Validation)Independent validation cohort analyzed with qPCR-based EpiCORE assay to confirm biomarker predictive accuracy.
Validation Cohort - PFS < 12 Months (Non-Responder)	–	Diagnostic Test: EpiCORE Assay (Targeted Sequencing / qPCR Validation)Independent validation cohort with poor PFS analyzed to assess specificity and model performance.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Patients diagnosed with Stage IV colorectal adenocarcinoma who received first-line FOLFOX or FOLFIRI chemotherapy and have available pre-treatment serum or plasma samples for cfDNA analysis.

Key inclusion criteria (5 listed)

Histologically confirmed metastatic colorectal adenocarcinoma (mCRC).
Received first-line chemotherapy (FOLFOX or FOLFIRI).
Availability of pre-treatment serum or plasma samples for cfDNA 5mC/5hmC analysis.
Documented radiologic or clinical response evaluation (RECIST 1.1 or PFS-based).
RAS/BRAF mutation status available.

Key exclusion criteria (4 listed)

Inadequate cfDNA yield or poor DNA quality.
Non-adenocarcinoma histology.
Active inflammatory or autoimmune disease that may alter cfDNA methylation.
Concomitant malignancy requiring systemic therapy.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
cfDNA 5mC/5hmC Sequencing (EpiCORE Discovery Phase)Genome-wide profiling of cfDNA methylation and hydroxymethylation from pre-treatment plasma to identify molecular determinants associated with chemotherapy efficacy (PFS ≥ 12M vs < 12M).	Diagnostic test	Discovery Cohort - PFS < 12 Months (Non-Responder), Discovery Cohort - PFS ≥ 12 Months (Responder)
EpiCORE Assay (Targeted Sequencing / qPCR Validation)Targeted validation of cfDNA 5mC/5hmC markers from discovery phase using sequencing and qPCR to build and validate a predictive model for first-line chemotherapy response.	Diagnostic test	Training Cohort - PFS < 12 Months (Non-Responder), Training Cohort - PFS ≥ 12 Months (Responder), Validation Cohort - PFS < 12 Months (Non-Responder), Validation Cohort - PFS ≥ 12 Months (Responder)

Primary outcome

Progression-Free Survival (PFS)
Time frame: Up to 36 months from initiation of first-line chemotherapy
Progression-free survival (PFS) is defined as the time from initiation of first-line chemotherapy (FOLFOX or FOLFIRI) to the date of documented disease progression or death from any cause, whichever occurs first. The primary objective of the EpiCORE study is to evaluate whether cfDNA 5mC/5hmC-based biomarker profiles (EpiCORE panel) are associated with differences in PFS among patients with metastatic colorectal cancer (mCRC).

1 secondary outcome

Overall Survival (OS):
Time frame: Up to 60 months from initiation of first-line chemotherapy

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
Background: PubMed 21319948Nelson MA, Shetty S, Kulakodlu M, Harley C, Seal B. A comparison of mortality and costs associated with FOLFOX versus FOLFIRI in stage IV colorectal cancer. J Med Econ. 2011;14(2):179-86. doi: 10.3111/13696998.2011.556693. Epub 2011 Feb 14.
Background: PubMed 37329889Bond MJG, Bolhuis K, Loosveld OJL, de Groot JWB, Droogendijk H, Helgason HH, Hendriks MP, Klaase JM, Kazemier G, Liem MSL, Rijken AM, Verhoef C, de Wilt JHW, de Jong KP, Gerhards MF, van Amerongen MJ, Engelbrecht MRW, van Lienden KP, Molenaar IQ, de Valk B, Haberkorn BCM, Kerver ED, Erdkamp F, van Alphen RJ, Mathijssen-van Stein D, Komurcu A, Lopez-Yurda M, Swijnenburg RJ, Punt CJA; Dutch Colorectal Cancer Study Group. First-line systemic treatment strategies in patients with initially unresectable colorectal cancer liver metastases (CAIRO5): an open-label, multicentre, randomised, controlled, phase 3 study from the Dutch Colorectal Cancer Group. Lancet Oncol. 2023 Jul;24(7):757-771. doi: 10.1016/S1470-2045(23)00219-X. Epub 2023 Jun 14.
Background: PubMed 39570583Bond MJG, Bolhuis K, Loosveld OJL, de Groot JWB, Droogendijk H, Helgason HH, Hendriks MP, Klaase JM, Kazemier G, Liem MSL, Rijken AM, Verhoef C, de Wilt JHW, de Jong KP, Gerhards MF, van Amerongen MJ, Engelbrecht MRW, van Lienden KP, Hermans JJ, Molenaar IQ, Grunhagen DJ, de Valk B, Haberkorn BCM, Kerver ED, Erdkamp F, van Alphen RJ, Mathijssen-van Stein D, Komurcu A, May AM, Swijnenburg RJ, Punt CJA; Dutch Colorectal Cancer Group. First-Line Systemic Treatment for Initially Unresectable Colorectal Liver Metastases: Post Hoc Analysis of the CAIRO5 Randomized Clinical Trial. JAMA Oncol. 2025 Jan 1;11(1):36-45. doi: 10.1001/jamaoncol.2024.5174.
Background: PubMed 30878317Neugut AI, Lin A, Raab GT, Hillyer GC, Keller D, O'Neil DS, Accordino MK, Kiran RP, Wright J, Hershman DL. FOLFOX and FOLFIRI Use in Stage IV Colon Cancer: Analysis of SEER-Medicare Data. Clin Colorectal Cancer. 2019 Jun;18(2):133-140. doi: 10.1016/j.clcc.2019.01.005. Epub 2019 Jan 31.
Background: PubMed 8667328Gibbons CE, Khan F. Dysphagia--a presenting symptom of forestier disease. J R Army Med Corps. 1996 Feb;142(1):32-3. doi: 10.1136/jramc-142-01-07.
Background: PubMed 38212123Guler GD, Ning Y, Coruh C, Mognol GP, Phillips T, Nabiyouni M, Hazen K, Scott A, Volkmuth W, Levy S. Plasma cell-free DNA hydroxymethylation profiling reveals anti-PD-1 treatment response and resistance biology in non-small cell lung cancer. J Immunother Cancer. 2024 Jan 11;12(1):e008028. doi: 10.1136/jitc-2023-008028.
Background: PubMed 33930176Ferrara R, Imbimbo M, Malouf R, Paget-Bailly S, Calais F, Marchal C, Westeel V. Single or combined immune checkpoint inhibitors compared to first-line platinum-based chemotherapy with or without bevacizumab for people with advanced non-small cell lung cancer. Cochrane Database Syst Rev. 2021 Apr 30;4(4):CD013257. doi: 10.1002/14651858.CD013257.pub3.
Background: PubMed 40375296Baldassarre G, L de la Serna I, Vallette FM. Death-ision: the link between cellular resilience and cancer resistance to treatments. Mol Cancer. 2025 May 15;24(1):144. doi: 10.1186/s12943-025-02339-1.
Background: PubMed 40055844Song D, Zhang Z, Zheng J, Zhang W, Cai J. 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation. Biomark Res. 2025 Mar 7;13(1):39. doi: 10.1186/s40364-025-00751-9.
Background: PubMed 39817679Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025 Jan-Feb;75(1):10-45. doi: 10.3322/caac.21871. Epub 2025 Jan 16.
Background: PubMed 38464122West-Szymanski DC, Zhang Z, Cui XL, Kowitwanich K, Gao L, Deng Z, Dougherty U, Williams C, Merkle S, Moore M, He C, Bissonnette M, Zhang W. Machine learning identifies cell-free DNA 5-hydroxymethylation biomarkers that detect occult colorectal cancer in PLCO Screening Trial subjects. bioRxiv [Preprint]. 2024 Feb 26:2024.02.25.581955. doi: 10.1101/2024.02.25.581955.
Background: PubMed 39393034West-Szymanski DC, Zhang Z, Cui XL, Kowitwanich K, Gao L, Deng Z, Dougherty U, Williams C, Merkle S, He C, Zhang W, Bissonnette M. 5-Hydroxymethylated Biomarkers in Cell-Free DNA Predict Occult Colorectal Cancer up to 36 Months Before Diagnosis in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. JCO Precis Oncol. 2024 Oct;8:e2400277. doi: 10.1200/PO.24.00277. Epub 2024 Oct 11.
Individual participant dataSharing planned: No. 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.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Ajay Goel, PhD contact

6263598111

ajgoel@coh.org

Ajay Goel, PhD principal investigator

City of Hope Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of CRC (Colorectal Cancer), run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ajay Goel, PhD (6263598111, ajgoel@coh.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) (time frame: Up to 36 months from initiation of first-line chemotherapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07224815, which also lists 17 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.