Colorectal CancerMIRRORNCT06204484
MRD-guided Deferred Adjuvant Therapy in Resectable Early-stage Colon Cancer
A study testing CAPEOX adjuvant therapy, deferred CAPEOX adjuvant therapy and mFOLFOXIRI intensive adjuvant therapy in people with Colorectal Cancer, run by Sun Yat-sen University at 1 site in China.
Trial summary
The aim of this clinical trial is to test whether minimal residual disease (MRD) status detected by circulating tumor DNA (ctDNA) could be used to guide precision therapy of post-surgery in colon cancer. The colon cancers are intended for resectable colon cancer of high-risk stage II and low-risk stage III status. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- CAPEOX adjuvant therapy, deferred CAPEOX adjuvant therapy and mFOLFOXIRI intensive adjuvant therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 349 participants
- Where
- 1 siteChina
- Study dates
- 26 Jul 2023to 31 Jul 2028
- Phase
- Interventional
- 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 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must fit all of the following inclusion criteria to be enrolled in this study:
- Over 18 years old (including 18 years old) and under 70 years old (including 70 years old) when signing the informed consent form;
- The Eastern Cooperative Oncology Group (ECOG) physical status scores are 0-1 and do not deteriorate within 2 weeks before enrollment. The expected survival time is no less than 12 weeks;
- Histological or cytological confirmed stage II high-risk and stage III low-risk none high microsatellite instability (MSI-H) colon adenocarcinoma according to the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) primary tumor, regional nodes, metastasis (TNM) stage (8th edition). High-risk factors for stage II patients include: T4, poorly differentiated histology (high-grade, excluding MSI-H status), vascular invasion, neural invasion, intestinal obstruction or tumor site perforation pre-operation, positive or unknown margins, insufficient margin distance and examined lymph nodes less than 12; Stage III low-risk patients include patients with T1-3 N1 (excluding T4 or N2).
- No evidence of distant metastasis (distant organ and/or distant lymph node metastasis) confirmed by comprehensive examination;
- The distal end of the tumor is ≥12cm from the anal edge evaluated by pre-operative endoscopy. If the endoscopy is absent before surgery, the distance could be evaluated by radiology or during the surgery;
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- Patients who have not received neoadjuvant therapy and can achieve R0 radical resection;
- Sufficient surgical fresh tissue samples for customized personalized MRD testing panels detected by whole exome sequencing (WES); available for preoperative blood, post-operative day (POD) 3-7 blood, and POD 21-30 blood samples for MRD testing;
- Females of the childbearing period should take appropriate contraceptive measures and should not breastfeed from the screening stage to 3 months post-treatment. Before starting treatment, a negative pregnancy test, or one of the following criteria should be confirmed for no risk of pregnancy:
- Post-menopause, defined as age greater than 50 years and amenorrhea for at least 12 months after cessation of all exogenous hormone replacement therapy.
- Women younger than 50 years who have been amenorrhea for 12 months or more after cessation of all exogenous hormone therapy and whose luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels are within laboratory postmenopausal reference values can also be considered as post-menopausal.
- Have undergone irreversible sterilization surgery, including hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, except bilateral tubal ligation.
- Male participants should use barrier contraception (i.e., condoms) from the screening stage to 3 months post-treatment;
- The participants volunteer to join in the study and signed the informed consent in writing;
- Patients who are suitable for CAPEOX and mFOLFOXIRI adjuvant therapy.
Who cannot join
- Participants who meet any of the following criteria are not eligible for this study:
- Received any of the following treatments:
- Received neoadjuvant therapy in the past;
- Previously received any systemic chemotherapy or immunotherapy for colon cancer;
- Previously received any radiotherapy for colon cancer;
- Undergone colon cancer surgery in the past;
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- Previously or concomitantly diagnosed of other malignant tumors (except for adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer);
- Patients with other histological types rather than adenocarcinoma (such as neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.);
- MSI-H/deficient mismatch repair (dMMR) patients;
- Pathological, clinical, or radiologic evidence of metastatic lesions, including isolated, distant, or discontinuous intra-abdominal metastases;
- Patients with multiple primary colorectal cancer;
- Received other parts of open surgery rather than the colon within 14 days prior to the patient's enrollment;
- Cannot provide surgical tissues for customized personalized MRD testing or fail to customize personalized MRD testing panels.
- Cannot provide pre-operative blood, POD 3-7 blood, and POD 21-30 for MRD testing.
- Suffer from other serious diseases that may affect the follow-up and short-term survival according to the judgment of the investigators;
- Any other medical conditions and social/psychological problems, which make the patient unfit to participate in this study;
- History of blood transfusion within 2 weeks before surgery or during surgery;
- Those who cannot afford contrast-enhanced magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT) for clinical follow-up;
- Previously used Chinese patent medicine (CPM) with anti-tumor effect. Those who have used CPM with anti-tumor effect for less than 7 days, and have stopped for over 2 weeks can be enrolled in the study;
- Have serious or uncontrolled systemic diseases (such as severe mental disease, neurological disease, epilepsy or dementia, unstable or uncompensated respiratory, cardiovascular, hepatic or renal diseases, left ventricular ejection fraction (LVEF) < 50%, evidence of uncontrolled hypertension [greater than or equal to CTCAE grade 3 hypertension despite drug therapy]); patients with dysphagia, active gastrointestinal disease, or other diseases that significantly affect drug absorption, distribution, metabolism, and excretion. Those who have ever undergone major gastrectomy;
- Fever and body temperature above 38°C within the past 1 week, or active infection with clinical significance. Active tuberculosis. Active fungal, bacterial, and/or viral infections requiring systemic treatment;
- Those with active bleeding or new thrombotic disease who are taking therapeutic anticoagulant drugs or have bleeding tendency;
- Those with severe clinical abnormalities in rhythm, conduction, or morphology on the resting electrocardiogram, such as complete left bundle branch block, second-degree cardiac block, clinically significant ventricular arrhythmia, or atrial fibrillation, unstable angina, congestive heart failure, chronic heart failure with New York Heart Association (NYHA) class ≥ 2;
- Myocardial infarction, coronary/peripheral artery bypass, or cerebrovascular accident occurred within 3 months;
- QT interval (QTc) ≥450ms for males and ≥470ms for females in 12-lead electrocardiogram;
- Presence of risk factors leading to prolongation of the QTc or arrhythmia, such as heart failure, ≥CTCAE (version 4.03) 2nd-degree hypokalemia (2nd-degree hypokalemia is defined as serum potassium < the lower limit -3.0mmol/L, with symptoms need treatment), congenital long QT syndrome, family history of long QT syndrome;
- Intake of any drug known to prolong the QT interval within 2 weeks before enrollment;
- Insufficiency of bone marrow reserve or organ function, reaching any of the following laboratory limits (without corrective treatment within 1 week before blood draw for laboratory examination):
- Absolute neutrophil count <1.5×109/L;
- Platelet count <90×109/L;
- Hemoglobin <90 g/L (<9 g/dL);
- Alanine aminotransferase >3 times the upper limit of normal (ULN);
- Aspartate aminotransferase>3×ULN
- Total bilirubin > 1.5×ULN;
- Creatinine > 1.5×ULN or creatinine clearance rate < 45 mL/min (calculated by Cockcroft-Gault formula);
- Serum albumin (ALB) <28 g/L;
- Female subjects who are pregnant, lactating, or planning pregnancy during the study;
- Other circumstances in which the researchers assess that participants are not fit for this study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Gong Chen, PhD, +86 20 87343584, chengong@sysucc.org.cn
Gong Chen, PhD
About this study
Official title: The Effectiveness of Deferred Adjuvant Therapy Guided by Dynamic Monitoring Minimal Residue Disease in Resectable High-risk Stage II and Low-risk Stage III Colon Cancer: an Open-label, Multicenter, Phase II Clinical Study
The aim of this clinical trial is to test whether minimal residual disease (MRD) status detected by circulating tumor DNA (ctDNA) could be used to guide precision therapy of post-surgery in colon cancer. The colon cancers are intended for resectable colon cancer of high-risk stage II and low-risk stage III status. The main questions it aims to answer are:
- Whether patients with MRD negative status could benefit from deferred adjuvant therapy.
- Whether patients with MRD positive status need intensive adjuvant therapy. The qualified participants will go through two different randomized groups according to the post-surgery 1-month MRD status. In MRD negative groups, participants will be divided into standard adjuvant therapy groups and deferred adjuvant therapy groups at 1:2 ratios. In MRD positive groups, participants will be divided into standard adjuvant therapy groups and intensive adjuvant therapy groups at 1:2 ratios. All the patients will receive MRD detection every 3 months and radiological evaluation every 6 months up to 3 years, and survival follow-up up to 5 years.
- Conditions
- Colorectal Cancer
- Being tested
- CAPEOX adjuvant therapy, deferred CAPEOX adjuvant therapy, mFOLFOXIRI intensive adjuvant therapy
- Keywords
- circulating tumor DNA, adjuvant therapy
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAPEOX adjuvant therapyOther
In MRD-/+ standard therapy groups, patients will receive 3-month CAPEOX therapy, regardless of the MRD status.
deferred CAPEOX adjuvant therapyOther
In MRD-negative deferred adjuvant therapy group, patients won't get the standard CAPEOX adjuvant therapy at first. When MRD negative status turns to positive status, the 3-month CAPEOX therapy will be arranged.
mFOLFOXIRI intensive adjuvant therapyOther
In the MRD+ intensive standard therapy group, which represents a high risk of recurrence, patients will receive 3-month mFOLFOXIRI intensive therapy, instead of the CAPEOX standard adjuvant therapy.
| Study group | Role | What they receive |
|---|---|---|
| MRD-negative standard adjuvant therapy | Active comparator | In MRD-negative standard therapy groups, patients will receive 3-month capecitabine and oxaliplatin (CAPEOX) therapy. Receives: Other: CAPEOX adjuvant therapy |
| MRD-negative deferred adjuvant therapy | Experimental | In MRD- deferred adjuvant therapy group, patients won't get the standard CAPEOX adjuvant therapy at first. When MRD negative status turns to positive status, the 3-month CAPEOX therapy will be arranged. Receives: Other: deferred CAPEOX adjuvant therapy |
| MRD-positive standard adjuvant therapy | Active comparator | In MRD-positive standard therapy groups, patients will receive 3-month CAPEOX therapy, regardless of the MRD status. Receives: Other: CAPEOX adjuvant therapy |
| MRD-positive intensive adjuvant therapy | Experimental | In the MRD+ intensive standard therapy group, which represents a high risk of recurrence, patients will receive 3-month modified folinic acid, fluorouracil, oxaliplatin and irinotecan (mFOLFOXIRI) intensive therapy, instead of the CAPEOX standard adjuvant therapy. Receives: Other: mFOLFOXIRI intensive adjuvant therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Relapse-free survival (RFS) time in MRD-negative groups
To evaluate the 3-year RFS time in MRD guided deferred adjuvant therapy groups
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.
Secondary outcomes (3)
Overall survival (OS) time in MRD-negative groups
To evaluate the 5-year OS time in MRD-guided deferred adjuvant therapy groups
Measured: From the date of randomization until the date of death from any cause, assessed up to 5 years.
RFS time in MRD-positive groups
To evaluate the 3-year RFS time in MRD-guided intensive adjuvant therapy groups
Measured: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.
OS time in MRD+ groups
To evaluate the 5-year OS time in MRD-guided deferred adjuvant therapy groups
Measured: From the date of randomization until the date of death from any cause, assessed up to 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2024
- Study start26 Jul 2023
- Primary completion31 Jul 2028 (estimated)
- Study completion31 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 349 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Collaborators
- Guangzhou Burning Rock Dx Co., Ltd.
- Responsible party
- Principal investigator, Gong Chen, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06204484
- Sponsor's protocol ID
- MIRROR
- Acronym
- MIRROR
- Status last verified
- Jan 2024
- First submitted
- 28 Nov 2023
- Last updated
- 12 Jan 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of Deferred Adjuvant Therapy Guided by Dynamic Monitoring Minimal Residue Disease in Resectable High-risk Stage II and Low-risk Stage III Colon Cancer: an Open-label, Multicenter, Phase II Clinical Study
- ClinicalTrials.gov ID
- NCT06204484
- Acronym / sponsor ID
- MIRROR / MIRROR
- Conditions
- Colorectal Cancer
- Keywords
- circulating tumor DNA, adjuvant therapy
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 349 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Collaborators
- Guangzhou Burning Rock Dx Co., Ltd.
- Study start
- 26 Jul 2023 (actual)
- Primary completion
- 31 Jul 2028 (estimated)
- Study completion
- 31 Jul 2028 (estimated)
- First posted
- 12 Jan 2024 (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 aim of this clinical trial is to test whether minimal residual disease (MRD) status detected by circulating tumor DNA (ctDNA) could be used to guide precision therapy of post-surgery in colon cancer. The colon cancers are intended for resectable colon cancer of high-risk stage II and low-risk stage III status. The main questions it aims to answer are:
- Whether patients with MRD negative status could benefit from deferred adjuvant therapy.
- Whether patients with MRD positive status need intensive adjuvant therapy. The qualified participants will go through two different randomized groups according to the post-surgery 1-month MRD status. In MRD negative groups, participants will be divided into standard adjuvant therapy groups and deferred adjuvant therapy groups at 1:2 ratios. In MRD positive groups, participants will be divided into standard adjuvant therapy groups and intensive adjuvant therapy groups at 1:2 ratios. All the patients will receive MRD detection every 3 months and radiological evaluation every 6 months up to 3 years, and survival follow-up up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| MRD-negative standard adjuvant therapy | Active comparator | Other: CAPEOX adjuvant therapyIn MRD-negative standard therapy groups, patients will receive 3-month capecitabine and oxaliplatin (CAPEOX) therapy. |
| MRD-negative deferred adjuvant therapy | Experimental | Other: deferred CAPEOX adjuvant therapyIn MRD- deferred adjuvant therapy group, patients won't get the standard CAPEOX adjuvant therapy at first. When MRD negative status turns to positive status, the 3-month CAPEOX therapy will be arranged. |
| MRD-positive standard adjuvant therapy | Active comparator | Other: CAPEOX adjuvant therapyIn MRD-positive standard therapy groups, patients will receive 3-month CAPEOX therapy, regardless of the MRD status. |
| MRD-positive intensive adjuvant therapy | Experimental | Other: mFOLFOXIRI intensive adjuvant therapyIn the MRD+ intensive standard therapy group, which represents a high risk of recurrence, patients will receive 3-month modified folinic acid, fluorouracil, oxaliplatin and irinotecan (mFOLFOXIRI) intensive therapy, instead of the CAPEOX standard adjuvant therapy. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Participants must fit all of the following inclusion criteria to be enrolled in this study:
- Over 18 years old (including 18 years old) and under 70 years old (including 70 years old) when signing the informed consent form;
- The Eastern Cooperative Oncology Group (ECOG) physical status scores are 0-1 and do not deteriorate within 2 weeks before enrollment. The expected survival time is no less than 12 weeks;
- Histological or cytological confirmed stage II high-risk and stage III low-risk none high microsatellite instability (MSI-H) colon adenocarcinoma according to the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) primary tumor, regional nodes, metastasis (TNM) stage (8th edition). High-risk factors for stage II patients include: T4, poorly differentiated histology (high-grade, excluding MSI-H status), vascular invasion, neural invasion, intestinal obstruction or tumor site perforation pre-operation, positive or unknown margins, insufficient margin distance and examined lymph nodes less than 12; Stage III low-risk patients include patients with T1-3 N1 (excluding T4 or N2).
- No evidence of distant metastasis (distant organ and/or distant lymph node metastasis) confirmed by comprehensive examination;
Key exclusion criteria (38 listed)
- Received any of the following treatments:
- Previously or concomitantly diagnosed of other malignant tumors (except for adequately treated cervical carcinoma in situ, basal or squamous cell skin cancer);
- Patients with other histological types rather than adenocarcinoma (such as neuroendocrine carcinoma, sarcoma, lymphoma, squamous cell carcinoma, etc.);
- MSI-H/deficient mismatch repair (dMMR) patients;
- Pathological, clinical, or radiologic evidence of metastatic lesions, including isolated, distant, or discontinuous intra-abdominal metastases;
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 |
|---|---|---|
| CAPEOX adjuvant therapyIn MRD-/+ standard therapy groups, patients will receive 3-month CAPEOX therapy, regardless of the MRD status. | Other | MRD-negative standard adjuvant therapy, MRD-positive standard adjuvant therapy |
| deferred CAPEOX adjuvant therapyIn MRD-negative deferred adjuvant therapy group, patients won't get the standard CAPEOX adjuvant therapy at first. When MRD negative status turns to positive status, the 3-month CAPEOX therapy will be arranged. | Other | MRD-negative deferred adjuvant therapy |
| mFOLFOXIRI intensive adjuvant therapyIn the MRD+ intensive standard therapy group, which represents a high risk of recurrence, patients will receive 3-month mFOLFOXIRI intensive therapy, instead of the CAPEOX standard adjuvant therapy. | Other | MRD-positive intensive adjuvant therapy |
Primary outcome
Relapse-free survival (RFS) time in MRD-negative groups
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.
To evaluate the 3-year RFS time in MRD guided deferred adjuvant therapy groups
3 secondary outcomes
Overall survival (OS) time in MRD-negative groups
Time frame: From the date of randomization until the date of death from any cause, assessed up to 5 years.
RFS time in MRD-positive groups
Time frame: From the date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.
OS time in MRD+ groups
Time frame: From the date of randomization until the date of death from any cause, assessed up to 5 years.
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 12 Jan 2024.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CAPEOX adjuvant therapy, deferred CAPEOX adjuvant therapy and mFOLFOXIRI intensive adjuvant therapy in people with Colorectal Cancer, run by Sun Yat-sen University at 1 site in China.
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 15 inclusion and 38 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 12 Jan 2024. 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 China. 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 Gong Chen, PhD (+86 20 87343584, chengong@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relapse-free survival (RFS) time in MRD-negative groups (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Jan 2024.