Colorectal CancerCIRCLENCT07224789
Liquid Biopsy for Early Detection of Colorectal Cancer Using Circular RNA
An observational study of Colorectal Cancer, run by City of Hope Medical Center at 1 site in United States.
Trial summary
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. This study aims to develop a non-invasive liquid biopsy assay using plasma-derived cell-free circular RNAs (cf-circRNAs) for early and accurate detection of colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- cf-circRNA assay
- How many people
- 600 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jan 2025to 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
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients with histologically confirmed colorectal adenocarcinoma (Stages I-III) Patients with benign colorectal diseases (adenoma, polyp) Healthy control individuals with no evidence of malignancy
Who may be able to join
- Adults (≥18 years old)
- Histologically confirmed colorectal cancer (Stage I-III)
- Availability of pre-treatment plasma samples
- Written informed consent provided
Who cannot join
- History of other active malignancies within the past 5 years
- Poor sample quality or hemolysis
- Inability to provide informed consent
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
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. This study aims to develop a non-invasive liquid biopsy assay using plasma-derived cell-free circular RNAs (cf-circRNAs) for early and accurate detection of colorectal cancer.
Read the detailed description
Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related mortality worldwide. Despite the proven benefit of screening colonoscopy, its invasive nature, high cost, and low adherence rates limit its use for population-level early detection. Current non-invasive screening tools, such as fecal occult blood testing and stool DNA assays, offer limited sensitivity, particularly for early-stage or right-sided colorectal tumors.
Therefore, there is a growing clinical need for a highly sensitive, minimally invasive, and patient-compliant diagnostic approach that can complement existing screening modalities.
Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs characterized by covalently closed loop structures formed through back-splicing. Unlike linear RNAs, circRNAs are resistant to exonuclease-mediated degradation and are remarkably stable in body fluids. They exhibit tissue- and cancer-specific expression patterns, suggesting strong potential as non-invasive biomarkers.
Emerging evidence demonstrates that cell-free circRNAs (cf-circRNAs) circulate in plasma or serum either freely or encapsulated within extracellular vesicles such as exosomes. These cf-circRNAs retain the molecular signatures of their tumor of origin and can be reliably quantified using reverse transcriptase-quantitative PCR (RT-qPCR) or next-generation sequencing (NGS)-based platforms.
The CIRCLED study (Circular RNA for Colorectal Cancer Detection) is designed as a multi-center, case-control, observational study aiming to (1) identify diagnostic circRNA candidates from RNA sequencing, and (2) validate a cf-circRNA diagnostic panel capable of differentiating CRC patients from healthy individuals and those with benign colorectal diseases.
- Conditions
- Colorectal Cancer
- Being tested
- cf-circRNA assay
- Keywords
- circRNA, Early cancer detection, non-coding RNA, CRC, liquid biopsy
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
cf-circRNA assayDiagnostic test
Circular RNA detection in plasma or serum by RT-qPCR
| Study group | Role | What they receive |
|---|---|---|
| Colorectal Cancer - Training Cohort | Patients with histologically confirmed colorectal adenocarcinoma (Stage I-III) enrolled in the training set. Plasma samples are collected before any surgery or therapy for cf-circRNA profiling. Receives: Diagnostic Test: cf-circRNA assay | |
| Non-Disease Control - Training Cohort | Healthy individuals with no prior malignancy or major systemic disease, age- and sex-matched to the CRC group, included in the training set. Receives: Diagnostic Test: cf-circRNA assay | |
| Colorectal Cancer - Validation Cohort | Independent cohort of patients with histologically confirmed colorectal adenocarcinoma (Stage I-III) from separate institutions, used to validate the diagnostic cf-circRNA signature. Plasma obtained prior to treatment. Receives: Diagnostic Test: cf-circRNA assay | |
| Non-Disease Control - Validation Cohort | Independent cohort of healthy participants without malignant or inflammatory bowel disease, serving as external validation controls. Receives: Diagnostic Test: cf-circRNA assay |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sensitivity
Proportion of early-stage (Stage I-II) colorectal cancer patients correctly identified as positive by the circRNA-based diagnostic model.
Measured: Through study completion, an average of 1 year
Secondary outcomes (2)
Specificity
True Negative Rate: the probability of a negative test result, conditioned on the individual truly being negative
Measured: Through study completion, an average of 1 year
Proportion of correct predictions (true positives and true negatives) among the total cases (i.e., accuracy)
A measure of trueness: proportion of correct predictions (both true positives and true negatives) among the total number of cases examined
Measured: Through study completion, an average of 1 year
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 start15 Jan 2025
- 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 (9)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies 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)
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
- NCT07224789
- Sponsor's protocol ID
- 23228/CIRCLE
- Acronym
- CIRCLE
- 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
Dong Y, He D, Peng Z, Peng W, Shi W, Wang J, Li B, Zhang C, Duan C. Circular RNAs in cancer: an emerging key player. J Hematol Oncol. 2017 Jan 3;10(1):2. doi: 10.1186/s13045-016-0370-2.
PubMed 28049499Qu S, Yang X, Li X, Wang J, Gao Y, Shang R, Sun W, Dou K, Li H. Circular RNA: A new star of noncoding RNAs. Cancer Lett. 2015 Sep 1;365(2):141-8. doi: 10.1016/j.canlet.2015.06.003. Epub 2015 Jun 5.
PubMed 26052092Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol. 2014 May;32(5):453-61. doi: 10.1038/nbt.2890.
PubMed 24811520Chen LY, Wang L, Ren YX, Pang Z, Liu Y, Sun XD, Tu J, Zhi Z, Qin Y, Sun LN, Li JM. The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1alpha translation. Mol Cancer. 2020 Nov 23;19(1):164. doi: 10.1186/s12943-020-01272-9.
PubMed 33225938Xu H, Liu Y, Cheng P, Wang C, Liu Y, Zhou W, Xu Y, Ji G. CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis. J Exp Clin Cancer Res. 2020 Dec 14;39(1):283. doi: 10.1186/s13046-020-01799-1.
PubMed 33317596Long F, Lin Z, Li L, Ma M, Lu Z, Jing L, Li X, Lin C. Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer. Mol Cancer. 2021 Feb 3;20(1):26. doi: 10.1186/s12943-021-01318-6.
PubMed 33536039Zhang Y, Luo J, Yang W, Ye WC. CircRNAs in colorectal cancer: potential biomarkers and therapeutic targets. Cell Death Dis. 2023 Jun 9;14(6):353. doi: 10.1038/s41419-023-05881-2.
PubMed 37296107Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019 Dec;16(12):713-732. doi: 10.1038/s41575-019-0189-8. Epub 2019 Aug 27.
PubMed 31455888Siegel 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
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
- Liquid Biopsy for Early Detection of Colorectal Cancer Using Circular RNA
- ClinicalTrials.gov ID
- NCT07224789
- Acronym / sponsor ID
- CIRCLE / 23228/CIRCLE
- Conditions
- Colorectal Cancer
- Keywords
- circRNA, Early cancer detection, non-coding RNA, CRC, liquid biopsy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Study start
- 15 Jan 2025 (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.
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. This study aims to develop a non-invasive liquid biopsy assay using plasma-derived cell-free circular RNAs (cf-circRNAs) for early and accurate detection of colorectal cancer.
Detailed description
Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related mortality worldwide. Despite the proven benefit of screening colonoscopy, its invasive nature, high cost, and low adherence rates limit its use for population-level early detection. Current non-invasive screening tools, such as fecal occult blood testing and stool DNA assays, offer limited sensitivity, particularly for early-stage or right-sided colorectal tumors.
Therefore, there is a growing clinical need for a highly sensitive, minimally invasive, and patient-compliant diagnostic approach that can complement existing screening modalities.
Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs characterized by covalently closed loop structures formed through back-splicing. Unlike linear RNAs, circRNAs are resistant to exonuclease-mediated degradation and are remarkably stable in body fluids. They exhibit tissue- and cancer-specific expression patterns, suggesting strong potential as non-invasive biomarkers.
Emerging evidence demonstrates that cell-free circRNAs (cf-circRNAs) circulate in plasma or serum either freely or encapsulated within extracellular vesicles such as exosomes. These cf-circRNAs retain the molecular signatures of their tumor of origin and can be reliably quantified using reverse transcriptase-quantitative PCR (RT-qPCR) or next-generation sequencing (NGS)-based platforms.
The CIRCLED study (Circular RNA for Colorectal Cancer Detection) is designed as a multi-center, case-control, observational study aiming to (1) identify diagnostic circRNA candidates from RNA sequencing, and (2) validate a cf-circRNA diagnostic panel capable of differentiating CRC patients from healthy individuals and those with benign colorectal diseases.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Colorectal Cancer - Training Cohort | – | Diagnostic Test: cf-circRNA assayPatients with histologically confirmed colorectal adenocarcinoma (Stage I-III) enrolled in the training set. Plasma samples are collected before any surgery or therapy for cf-circRNA profiling. |
| Non-Disease Control - Training Cohort | – | Diagnostic Test: cf-circRNA assayHealthy individuals with no prior malignancy or major systemic disease, age- and sex-matched to the CRC group, included in the training set. |
| Colorectal Cancer - Validation Cohort | – | Diagnostic Test: cf-circRNA assayIndependent cohort of patients with histologically confirmed colorectal adenocarcinoma (Stage I-III) from separate institutions, used to validate the diagnostic cf-circRNA signature. Plasma obtained prior to treatment. |
| Non-Disease Control - Validation Cohort | – | Diagnostic Test: cf-circRNA assayIndependent cohort of healthy participants without malignant or inflammatory bowel disease, serving as external validation controls. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with histologically confirmed colorectal adenocarcinoma (Stages I-III) Patients with benign colorectal diseases (adenoma, polyp) Healthy control individuals with no evidence of malignancy
Key inclusion criteria (4 listed)
- Adults (≥18 years old)
- Histologically confirmed colorectal cancer (Stage I-III)
- Availability of pre-treatment plasma samples
- Written informed consent provided
Key exclusion criteria (3 listed)
- History of other active malignancies within the past 5 years
- Poor sample quality or hemolysis
- Inability to provide informed consent
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 |
|---|---|---|
| cf-circRNA assayCircular RNA detection in plasma or serum by RT-qPCR | Diagnostic test | Colorectal Cancer - Training Cohort, Colorectal Cancer - Validation Cohort, Non-Disease Control - Training Cohort, Non-Disease Control - Validation Cohort |
Primary outcome
Sensitivity
Time frame: Through study completion, an average of 1 year
Proportion of early-stage (Stage I-II) colorectal cancer patients correctly identified as positive by the circRNA-based diagnostic model.
2 secondary outcomes
Specificity
Time frame: Through study completion, an average of 1 year
Proportion of correct predictions (true positives and true negatives) among the total cases (i.e., accuracy)
Time frame: Through study completion, an average of 1 year
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 28049499Dong Y, He D, Peng Z, Peng W, Shi W, Wang J, Li B, Zhang C, Duan C. Circular RNAs in cancer: an emerging key player. J Hematol Oncol. 2017 Jan 3;10(1):2. doi: 10.1186/s13045-016-0370-2.
- Background: PubMed 26052092Qu S, Yang X, Li X, Wang J, Gao Y, Shang R, Sun W, Dou K, Li H. Circular RNA: A new star of noncoding RNAs. Cancer Lett. 2015 Sep 1;365(2):141-8. doi: 10.1016/j.canlet.2015.06.003. Epub 2015 Jun 5.
- Background: PubMed 24811520Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol. 2014 May;32(5):453-61. doi: 10.1038/nbt.2890.
- Background: PubMed 33225938Chen LY, Wang L, Ren YX, Pang Z, Liu Y, Sun XD, Tu J, Zhi Z, Qin Y, Sun LN, Li JM. The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1alpha translation. Mol Cancer. 2020 Nov 23;19(1):164. doi: 10.1186/s12943-020-01272-9.
- Background: PubMed 33317596Xu H, Liu Y, Cheng P, Wang C, Liu Y, Zhou W, Xu Y, Ji G. CircRNA_0000392 promotes colorectal cancer progression through the miR-193a-5p/PIK3R3/AKT axis. J Exp Clin Cancer Res. 2020 Dec 14;39(1):283. doi: 10.1186/s13046-020-01799-1.
- Background: PubMed 33536039Long F, Lin Z, Li L, Ma M, Lu Z, Jing L, Li X, Lin C. Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer. Mol Cancer. 2021 Feb 3;20(1):26. doi: 10.1186/s12943-021-01318-6.
- Background: PubMed 37296107Zhang Y, Luo J, Yang W, Ye WC. CircRNAs in colorectal cancer: potential biomarkers and therapeutic targets. Cell Death Dis. 2023 Jun 9;14(6):353. doi: 10.1038/s41419-023-05881-2.
- Background: PubMed 31455888Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019 Dec;16(12):713-732. doi: 10.1038/s41575-019-0189-8. Epub 2019 Aug 27.
- 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.
- 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 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 4 inclusion and 3 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 Goel Ajay, PhD (626-218-3452, ajgoel@coh.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sensitivity (time frame: Through study completion, an average of 1 year). 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 NCT07224789, which also lists 9 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.