CRC (Colorectal Cancer)EpiDRIVENCT07224841
Development of a cfDNA 5mC/5hmC-based Biomarker Panel to Predict Targeted Therapy Efficacy in mCRC
An observational study of CRC (Colorectal Cancer), run by City of Hope Medical Center at 1 site in United States.
Trial summary
The EpiDRIVE study aims to identify cfDNA-based epigenetic determinants of response in metastatic colorectal cancer (mCRC) patients treated with EGFR- or VEGF-targeted therapy. By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to develop a predictive biomarker panel… 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 (EpiDRIVE Discovery Phase) and EpiDRIVE Assay (Targeted Sequencing / qPCR Validation)
- How many people
- 500 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 EGFR-targeted or VEGF-targeted therapy and had available pre-treatment plasma samples for cfDNA analysis.
Who may be able to join
- Histologically confirmed metastatic colorectal adenocarcinoma (mCRC).
- Received EGFR-targeted therapy (cetuximab/panitumumab) or VEGF-targeted therapy (bevacizumab).
- Availability of pre-treatment plasma sample for cfDNA analysis.
- Documented radiologic response evaluation (RECIST 1.1).
- RAS/BRAF mutation status known.
Who cannot join
- Inadequate cfDNA quality or low cfDNA yield.
- Non-adenocarcinoma histology.
- Concurrent or prior other active malignancy.
- Active inflammatory or autoimmune disease affecting cfDNA methylation profiles.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
City of Hope Medical Center
Duarte, California, 91016
Ajay Goel, PhD, 626-218-3452, ajgoel@coh.org
About this study
Official title: Development of a cfDNA 5mC/5hmC-based Epigenetic Biomarker Panel to Identify Determinants of Response In VEGF/EGFR-targeted Therapy for Metastatic Colorectal Cancer
The EpiDRIVE study aims to identify cfDNA-based epigenetic determinants of response in metastatic colorectal cancer (mCRC) patients treated with EGFR- or VEGF-targeted therapy.
By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to develop a predictive biomarker panel capable of differentiating responders from non-responders to targeted therapy.
Read the detailed description
Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer-related death. Although targeted agents such as anti-EGFR (cetuximab, panitumumab) and anti-VEGF (bevacizumab) therapies have improved survival, treatment response varies widely even among molecularly defined subgroups.
Traditional biomarkers, including RAS/BRAF mutation and tumor sidedness, fail to accurately predict therapeutic efficacy.
Recent studies highlight the potential of cell-free DNA (cfDNA) methylation (5mC) and hydroxymethylation (5hmC) as sensitive, non-invasive indicators of tumor biology and treatment dynamics.
The EpiDRIVE study integrates cfDNA 5mC/5hmC sequencing and targeted validation to discover and verify epigenetic determinants of therapeutic response.
Discovery phase: Whole-genome 5mC/5hmC profiling to identify differentially modified regions between responders and non-responders.
Training phase: Targeted sequencing to establish a predictive cfDNA epigenetic panel (EpiDRIVE panel).
Validation phase: qPCR-based validation of selected markers in an independent cohort to confirm predictive accuracy.
This study aims to provide a non-invasive biomarker framework to predict and monitor efficacy of EGFR- and VEGF-targeted therapies in mCRC, ultimately guiding personalized treatment selection.
- Conditions
- CRC (Colorectal Cancer)
- Being tested
- cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase), EpiDRIVE Assay (Targeted Sequencing / qPCR Validation)
- Keywords
- mCRC, Target therapy, 5mc/5hmc, 5-hydroxymethylation, Metastatic colorectal cancer, anti-EGFR therapy, anti-VEGF therapy, RAS/BRAF mutation, 5-methylcytosine
- 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 (EpiDRIVE Discovery Phase)Diagnostic test
High-throughput genome-wide sequencing of cfDNA methylation (5mC) and hydroxymethylation (5hmC) profiles from pre-treatment plasma samples in the discovery cohort to identify epigenetic determinants of targeted-therapy response (PFS ≥ 12 months vs < 12 months).
EpiDRIVE Assay (Targeted Sequencing / qPCR Validation)Diagnostic test
Targeted sequencing or qPCR-based validation of cfDNA 5mC/5hmC markers identified from the discovery phase to develop and validate a predictive biomarker model discriminating patients with long vs short progression-free survival after EGFR-/VEGF-targeted therapy.
| Study group | Role | What they receive |
|---|---|---|
| Discovery Cohort - Long PFS Group (Responder) | Patients with metastatic colorectal cancer (mCRC) who received EGFR- or VEGF-targeted therapy and achieved a progression-free survival (PFS) ≥ 12 months, classified as clinical responders.
Pre-treatment plasma cfDNA samples were analyzed by genome-wide 5mC/5hmC sequencing to identify epigenetic determinants associated with durable treatment response. Receives: Diagnostic Test: cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase) | |
| Discovery Cohort - Short PFS Group (Non-Responder) | Patients with mCRC who received EGFR- or VEGF-targeted therapy and showed progression-free survival (PFS) < 12 months, classified as non-responders.
Pre-treatment cfDNA samples were analyzed using genome-wide 5mC/5hmC sequencing and compared with long-PFS responders to identify differential methylation and hydroxymethylation patterns associated with resistance. Receives: Diagnostic Test: cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase) | |
| Training Cohort - Long PFS Group (Responder) | Independent mCRC cohort with PFS ≥ 12 months following EGFR- or VEGF-targeted therapy.
Candidate cfDNA 5mC/5hmC markers identified in the discovery phase were validated using targeted sequencing (EpiDRIVE assay) to construct the predictive epigenetic biomarker panel. Receives: Diagnostic Test: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation) | |
| Training Cohort - Short PFS Group (Non-Responder) | Independent mCRC patients with PFS < 12 months after targeted therapy. Targeted sequencing using the EpiDRIVE assay was conducted to refine and optimize the predictive model by comparing short- vs long-PFS cases. Receives: Diagnostic Test: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation) | |
| Validation Cohort - Long PFS Group (Responder) | Separate validation cohort of mCRC patients achieving PFS ≥ 12 months under EGFR- or VEGF-targeted therapy.
qPCR-based EpiDRIVE assay was used to confirm predictive accuracy of the cfDNA 5mC/5hmC biomarker panel in identifying durable responders. Receives: Diagnostic Test: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation) | |
| Validation Cohort - Short PFS Group (Non-Responder) | Independent validation cohort of mCRC patients with PFS < 12 months after targeted therapy.
cfDNA was analyzed using the qPCR-based EpiDRIVE assay to assess model specificity and distinguish non-responders from long-term responders. Receives: Diagnostic Test: EpiDRIVE 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) according to cfDNA 5mC/5hmC biomarker profile
Progression-free survival (PFS) among patients with metastatic colorectal cancer (mCRC) receiving EGFR- or VEGF-targeted therapy, stratified by cfDNA 5mC/5hmC-based biomarker status.
Measured: Up to 36 months from therapy initiation
Secondary outcomes (1)
Overall Survival (OS)
Time from initiation of EGFR- or VEGF-targeted therapy to death from any cause. Overall survival will be analyzed in relation to cfDNA 5mC/5hmC biomarker-defined groups (high vs low EpiDRIVE score) to assess whether epigenetic cfDNA profiles are associated with differences in survival outcomes.
Measured: Up to 60 months from therapy initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- 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 (15)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
- 500 participants (estimated)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ajay Goel, PhD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07224841
- Sponsor's protocol ID
- 23228/EpiDRIVE
- Acronym
- EpiDRIVE
- 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
Xu C, Mannucci A, Esposito F, Oliveres H, Alonso-Orduna V, Yubero A, Fernandez-Martos C, Salud A, Gallego J, Martin-Richard M, Fernandez-Plana J, Guillot M, Aparicio J, Fakih M, Kopetz S, Feliu J, Maurel J, Goel A. An Exosome-Based Liquid Biopsy Predicts Depth of Response and Survival Outcomes to Cetuximab and Panitumumab in Metastatic Colorectal Cancer: The EXONERATE Study. Clin Cancer Res. 2025 Mar 17;31(6):1002-1015. doi: 10.1158/1078-0432.CCR-24-1934.
PubMed 39820673Koroukian SM, Booker BD, Vu L, Schumacher FR, Rose J, Cooper GS, Selfridge JE, Markt SC. Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer. JAMA Netw Open. 2023 Jan 3;6(1):e2250030. doi: 10.1001/jamanetworkopen.2022.50030.
PubMed 36656585Tirendi 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 37538108Xie 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 32296018Cai Z, Zhang J, He Y, Xia L, Dong X, Chen G, Zhou Y, Hu X, Zhong S, Wang Y, Chen H, Xie D, Liu X, Liu J. Liquid biopsy by combining 5-hydroxymethylcytosine signatures of plasma cell-free DNA and protein biomarkers for diagnosis and prognosis of hepatocellular carcinoma. ESMO Open. 2021 Feb;6(1):100021. doi: 10.1016/j.esmoop.2020.100021. Epub 2021 Jan 25.
PubMed 33508734Zeng 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 30922396West-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 39393034West-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 38464122Siegel 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 39817679Song 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 40055844Baldassarre 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 40375296Ferrara 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 33930176Guler 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 38212123Shao J, Xu Y, Olsen RJ, Kasparian S, Sun K, Mathur S, Zhang J, He C, Chen SH, Bernicker EH, Li Z. 5-Hydroxymethylcytosine in Cell-Free DNA Predicts Immunotherapy Response in Lung Cancer. Cells. 2024 Apr 19;13(8):715. doi: 10.3390/cells13080715.
PubMed 38667328Li Q, Huang CC, Huang S, Tian Y, Huang J, Bitaraf A, Dong X, Nevalanen MT, Patel M, Wong J, Zhang J, Manley BJ, Park JY, Kohli M, Gore EM, Kilari D, Wang L. 5-hydroxymethylcytosine sequencing in plasma cell-free DNA identifies unique epigenomic features in prostate cancer patients resistant to androgen deprivation therapies. medRxiv [Preprint]. 2024 Oct 17:2023.10.13.23296758. doi: 10.1101/2023.10.13.23296758.
PubMed 37904926
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 Identify Determinants of Response In VEGF/EGFR-targeted Therapy for Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT07224841
- Acronym / sponsor ID
- EpiDRIVE / 23228/EpiDRIVE
- Conditions
- CRC (Colorectal Cancer)
- Keywords
- mCRC, Target therapy, 5mc/5hmc, 5-hydroxymethylation, Metastatic colorectal cancer, anti-EGFR therapy, anti-VEGF therapy, RAS/BRAF mutation
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 500 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 EpiDRIVE study aims to identify cfDNA-based epigenetic determinants of response in metastatic colorectal cancer (mCRC) patients treated with EGFR- or VEGF-targeted therapy.
By integrating 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) profiling, this study seeks to develop a predictive biomarker panel capable of differentiating responders from non-responders to targeted therapy.
Detailed description
Metastatic colorectal cancer (mCRC) remains one of the leading causes of cancer-related death. Although targeted agents such as anti-EGFR (cetuximab, panitumumab) and anti-VEGF (bevacizumab) therapies have improved survival, treatment response varies widely even among molecularly defined subgroups.
Traditional biomarkers, including RAS/BRAF mutation and tumor sidedness, fail to accurately predict therapeutic efficacy.
Recent studies highlight the potential of cell-free DNA (cfDNA) methylation (5mC) and hydroxymethylation (5hmC) as sensitive, non-invasive indicators of tumor biology and treatment dynamics.
The EpiDRIVE study integrates cfDNA 5mC/5hmC sequencing and targeted validation to discover and verify epigenetic determinants of therapeutic response.
Discovery phase: Whole-genome 5mC/5hmC profiling to identify differentially modified regions between responders and non-responders.
Training phase: Targeted sequencing to establish a predictive cfDNA epigenetic panel (EpiDRIVE panel).
Validation phase: qPCR-based validation of selected markers in an independent cohort to confirm predictive accuracy.
This study aims to provide a non-invasive biomarker framework to predict and monitor efficacy of EGFR- and VEGF-targeted therapies in mCRC, ultimately guiding personalized treatment selection.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Discovery Cohort - Long PFS Group (Responder) | – | Diagnostic Test: cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase)Patients with metastatic colorectal cancer (mCRC) who received EGFR- or VEGF-targeted therapy and achieved a progression-free survival (PFS) ≥ 12 months, classified as clinical responders. Pre-treatment plasma cfDNA samples were analyzed by genome-wide 5mC/5hmC sequencing to identify epigenetic determinants associated with durable treatment response. |
| Discovery Cohort - Short PFS Group (Non-Responder) | – | Diagnostic Test: cfDNA 5mC/5hmC Sequencing (EpiDRIVE Discovery Phase)Patients with mCRC who received EGFR- or VEGF-targeted therapy and showed progression-free survival (PFS) < 12 months, classified as non-responders. Pre-treatment cfDNA samples were analyzed using genome-wide 5mC/5hmC sequencing and compared with long-PFS responders to identify differential methylation and hydroxymethylation patterns associated with resistance. |
| Training Cohort - Long PFS Group (Responder) | – | Diagnostic Test: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation)Independent mCRC cohort with PFS ≥ 12 months following EGFR- or VEGF-targeted therapy. Candidate cfDNA 5mC/5hmC markers identified in the discovery phase were validated using targeted sequencing (EpiDRIVE assay) to construct the predictive epigenetic biomarker panel. |
| Training Cohort - Short PFS Group (Non-Responder) | – | Diagnostic Test: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation)Independent mCRC patients with PFS < 12 months after targeted therapy. Targeted sequencing using the EpiDRIVE assay was conducted to refine and optimize the predictive model by comparing short- vs long-PFS cases. |
| Validation Cohort - Long PFS Group (Responder) | – | Diagnostic Test: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation)Separate validation cohort of mCRC patients achieving PFS ≥ 12 months under EGFR- or VEGF-targeted therapy. qPCR-based EpiDRIVE assay was used to confirm predictive accuracy of the cfDNA 5mC/5hmC biomarker panel in identifying durable responders. |
| Validation Cohort - Short PFS Group (Non-Responder) | – | Diagnostic Test: EpiDRIVE Assay (Targeted Sequencing / qPCR Validation)Independent validation cohort of mCRC patients with PFS < 12 months after targeted therapy. cfDNA was analyzed using the qPCR-based EpiDRIVE assay to assess model specificity and distinguish non-responders from long-term responders. |
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 EGFR-targeted or VEGF-targeted therapy and had available pre-treatment plasma samples for cfDNA analysis.
Key inclusion criteria (5 listed)
- Histologically confirmed metastatic colorectal adenocarcinoma (mCRC).
- Received EGFR-targeted therapy (cetuximab/panitumumab) or VEGF-targeted therapy (bevacizumab).
- Availability of pre-treatment plasma sample for cfDNA analysis.
- Documented radiologic response evaluation (RECIST 1.1).
- RAS/BRAF mutation status known.
Key exclusion criteria (4 listed)
- Inadequate cfDNA quality or low cfDNA yield.
- Non-adenocarcinoma histology.
- Concurrent or prior other active malignancy.
- Active inflammatory or autoimmune disease affecting cfDNA methylation profiles.
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 (EpiDRIVE Discovery Phase)High-throughput genome-wide sequencing of cfDNA methylation (5mC) and hydroxymethylation (5hmC) profiles from pre-treatment plasma samples in the discovery cohort to identify epigenetic determinants of targeted-therapy response (PFS ≥ 12 months vs < 12 months). | Diagnostic test | Discovery Cohort - Long PFS Group (Responder), Discovery Cohort - Short PFS Group (Non-Responder) |
| EpiDRIVE Assay (Targeted Sequencing / qPCR Validation)Targeted sequencing or qPCR-based validation of cfDNA 5mC/5hmC markers identified from the discovery phase to develop and validate a predictive biomarker model discriminating patients with long vs short progression-free survival after EGFR-/VEGF-targeted therapy. | Diagnostic test | Training Cohort - Long PFS Group (Responder), Training Cohort - Short PFS Group (Non-Responder), Validation Cohort - Long PFS Group (Responder), Validation Cohort - Short PFS Group (Non-Responder) |
Primary outcome
Progression-Free Survival (PFS) according to cfDNA 5mC/5hmC biomarker profile
Time frame: Up to 36 months from therapy initiation
Progression-free survival (PFS) among patients with metastatic colorectal cancer (mCRC) receiving EGFR- or VEGF-targeted therapy, stratified by cfDNA 5mC/5hmC-based biomarker status.
1 secondary outcome
Overall Survival (OS)
Time frame: Up to 60 months from therapy initiation
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 39820673Xu C, Mannucci A, Esposito F, Oliveres H, Alonso-Orduna V, Yubero A, Fernandez-Martos C, Salud A, Gallego J, Martin-Richard M, Fernandez-Plana J, Guillot M, Aparicio J, Fakih M, Kopetz S, Feliu J, Maurel J, Goel A. An Exosome-Based Liquid Biopsy Predicts Depth of Response and Survival Outcomes to Cetuximab and Panitumumab in Metastatic Colorectal Cancer: The EXONERATE Study. Clin Cancer Res. 2025 Mar 17;31(6):1002-1015. doi: 10.1158/1078-0432.CCR-24-1934.
- Background: PubMed 36656585Koroukian SM, Booker BD, Vu L, Schumacher FR, Rose J, Cooper GS, Selfridge JE, Markt SC. Receipt of Targeted Therapy and Survival Outcomes in Patients With Metastatic Colorectal Cancer. JAMA Netw Open. 2023 Jan 3;6(1):e2250030. doi: 10.1001/jamanetworkopen.2022.50030.
- Background: PubMed 37538108Tirendi 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.
- Background: PubMed 32296018Xie 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.
- Background: PubMed 33508734Cai Z, Zhang J, He Y, Xia L, Dong X, Chen G, Zhou Y, Hu X, Zhong S, Wang Y, Chen H, Xie D, Liu X, Liu J. Liquid biopsy by combining 5-hydroxymethylcytosine signatures of plasma cell-free DNA and protein biomarkers for diagnosis and prognosis of hepatocellular carcinoma. ESMO Open. 2021 Feb;6(1):100021. doi: 10.1016/j.esmoop.2020.100021. Epub 2021 Jan 25.
- Background: PubMed 30922396Zeng 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.
- 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.
- 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 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 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 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 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.
- 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 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 (626-359-8111, 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) according to cfDNA 5mC/5hmC biomarker profile (time frame: Up to 36 months from therapy initiation). 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 NCT07224841, which also lists 15 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.