High-risk Stage II Colorectal CancerPhase 3NCT05954078

Circulating Tumor DNA Methylation Guided Postoperative Adjuvant Chemotherapy for High-risk Stage II/III Colorectal Cancer

A Phase 3 study testing mFOLFIRINOX adjuvant chemotherapy and mFOLFOX6/XELOX adjuvant chemotherapy in people with High-risk Stage II Colorectal Cancer and Stage III Colorectal Cancer, run by Fudan University at 1 site in China.

Recruiting

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

Sites and contacts

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 80 years
Conditions the study is for: High-risk Stage II Colorectal Cancer, Stage III Colorectal Cancer, Circulating Tumor DNA Methylation
What is being tested?: mFOLFIRINOX adjuvant chemotherapy and mFOLFOX6/XELOX adjuvant chemotherapy
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 340 participants
Where: 1 siteChina
Study dates: 1 Aug 2023to Jun 2028
Phase: Phase 3
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 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients who have been histopathologically diagnosed with colorectal adenocarcinoma;
Patients who have undergone radical curative resection of the primary tumors;
Patients with CRC of high-risk stage II and stage III based on final findings (UICC TNM Classification, 8th Edition);
Patients who tested positive for ctDNA methylation at 5-7 days after surgery prior to enrollment;
Patients with no obvious relapse confirmed by chest, abdominal, and pelvic CT scans, etc.;
Patients aged ≥ 18 and ≤80 years old, regardless of gender;

Show all 11Show fewer

Patients with expected survival of more than 12 months;
Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1;
Patients who have no severe disorder in major organs (such as the bone marrow, heart, lungs, liver, and kidneys) and meet the following criteria: Neutrophil count ≥ 1,500/mm3, Platelet count ≥ 100,000/mm3, Hemoglobin ≥ 8.0 g/dL, Serum creatinine ≤ 1.5 mg/dL, Total bilirubin ≤ 1.5 mg/dL, ALT and AST ≤ 100 U/L
Patients with no diarrhea or stomatitis of Grade 2 or severer according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0;
Patients who voluntarily gave written consent to participate in the trial after receiving a thorough explanation of the trial before enrolling in the trial

Who cannot join

Neoadjuvant therapy performed before operation;
Blood transfusion performed during operation or within 2 weeks before operation;
Incomplete baseline samples, including preoperative plasma samples and plasma samples 5-7 days after operation;
Pregnant or lactating women who have fertility and do not take adequate contraceptive measures;
Have a history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or non melanoma skin cancer;
Primary brain tumor or central nerve metastasis is not under control, with obvious intracranial hypertension or neuropsychiatric symptoms;

Show all 9Show fewer

Patients with the following serious or uncontrollable diseases: severe heart disease, the condition is still unstable after treatment, including myocardial infarction, congestive heart failure, unstable angina pectoris, pericardial effusion with obvious symptoms or unstable arrhythmia within 6 months before enrollment; definite neuropathy or psychosis, including dementia or seizures; severe or uncontrolled infection; active disseminated intravascular coagulation and obvious bleeding tendency;
Significant impairment of important organ function;
Other conditions in which the investigator believes that the patient should not participate in this trial

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

Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 200032
Junjie Peng, MD, PhD, 86-18017317122, pengjj67@hotmail.com
Shaobo Mo, MD, PhD, 86-18121290562, shaobom@126.com
Recruiting

Other trials in China

About this study

Official title: Circulating Tumor DNA Methylation Guided Postoperative Adjuvant Chemotherapy for High-risk Stage II/III Colorectal Cancer: A Multicenter, Prospective, Randomized Controlled Cohort Study (FINE Trial)

Colorectal cancer (CRC) is one of the most common gastrointestinal tumors. According to the latest cancer report, the incidence and mortality rates of CRC are both ranked top 5 among malignant tumors worldwide and continue to rise. Patients who receive treatment in the early stage (stage I) have a 5-year survival rate of approximately 90%. However, for high-risk stage II and III colorectal cancer patients, the 5-year survival rate is only 40%-70%, and almost half of the patients experience postoperative recurrence and metastasis.

Evidence suggests that Stage III CRC patients can benefit from standard adjuvant chemotherapy. It is worth noting that some high-risk stage II patients, especially those with T4N0, have a poorer prognosis compared to stage IIIA (T1-2N+). Adjuvant chemotherapy is now also recommended for postoperative cases of high-risk stage II CRC. Given the high effectiveness of the three-drug FOLFOXIRI regimen in treating metastatic CRC and the success of adjuvant chemotherapy in treating pancreatic cancer, the combination of 5-fluorouracil, oxaliplatin, and irinotecan may have a synergistic effect.

Extensive study results have shown that: (a) The status of ctDNA methylation after surgery is significantly correlated with patient prognosis, and patients who are positive for ctDNA methylation in the first 1-4 weeks after surgery (before adjuvant chemotherapy) have a poor prognosis. (b) Patients who are ctDNA methylation positive in the first 1-4 weeks after surgery (before adjuvant chemotherapy) can benefit from adjuvant chemotherapy, and achieving ctDNA methylation negativity through adjuvant chemotherapy significantly improves patient prognosis. This project focuses on exploring the optimized mode of postoperative adjuvant chemotherapy for high-risk stage II and III CRC guided by ctDNA methylation, which has high scientific and innovative value.

This multicenter, prospective, and randomized controlled cohort study uses a single-tube methylation-specific quantitative PCR (mqMSP) detection, which detects 10 different methylation markers and can quantitatively analyze plasma samples containing tumor DNA as low as 0.05%. This study will use this ctDNA methylation detection technology to perform quantitative detection of ctDNA methylation in the plasma of enrolled patients, and explore the effect of different chemotherapy regimens on ctDNA clearance rate and the prognostic value for ctDNA positive patients. We hope to screen out high-risk populations for recurrence through postoperative ctDNA testing, and administer more intensive chemotherapy regimens (chemotherapy upgrading) as early as possible to improve ctDNA clearance rate and patient prognosis.

Conditions: High-risk Stage II Colorectal Cancer, Stage III Colorectal Cancer, Circulating Tumor DNA Methylation
Being tested: mFOLFIRINOX adjuvant chemotherapy, mFOLFOX6/XELOX adjuvant chemotherapy
Medical subject headings: Colorectal Neoplasms

What participants receive

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

mFOLFIRINOX adjuvant chemotherapyDrug
Also called Oxaliplatin, Irinotecan, Leucovorin, 5-Fluorouracil
mFOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 6 cycles
mFOLFOX6/XELOX adjuvant chemotherapyDrug
Also called Oxaliplatin, Leucovorin, 5-Fluorouracil
mFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 400mg/m2 infusion, and 2400mg/m2 as a 46-hour continuous infusion on day 1) for 12 cycles or XELOX (oxaliplatin 130mg/m2, ivgtt, Q3w; capecitabine 1000mg/m2, p.o, Q3w) for 8 cycles

Study groups in NCT05954078
Study group	Role	What they receive
mFOLFIRINOX adjuvant chemotherapy	Experimental	Patients will receive mFOLFIRINOX once every two weeks for 6 cycles as adjuvant chemotherapy, after which a blood test is conducted to check the status of ctDNA. If the ctDNA remains positive, the treatment continues for another 6 cycles. If the ctDNA becomes negative, then maintenance chemotherapy with single-agent capecitabine is given once every 21 days for 4 cycles. Receives: Drug: mFOLFIRINOX adjuvant chemotherapy
mFOLFOX6/XELOX adjuvant chemotherapy	Active comparator	Patients will receive mFOLFOX6 once every two weeks for 6 cycles or XELOX once every three weeks for 4 cycles as adjuvant chemotherapy. After the treatment, a blood test is conducted to check the status of ctDNA. If the ctDNA remains positive, the treatment continues with another 6 cycles of mFOLFOX 6 or 4 cycles of XELOX given once every 21 days. If the ctDNA becomes negative, then maintenance chemotherapy with single-agent capecitabine is given once every 21 days for 4 cycles. Receives: Drug: mFOLFOX6/XELOX adjuvant chemotherapy

What is being measured

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

ctDNA clearance rate
The rate of ctDNA positive before chemotherapy that turns negative after adjuvant chemotherapy
Measured: ctDNA clearance rate after 3 months of chemotherapy (6 cycles or 4 cycles for chemotherapy); ctDNA clearance rate after 6 months of chemotherapy (12 cycles or 8 cycles for chemotherapy)

Secondary outcomes (4)

Disease-free survival (DFS)
Defined as the time from randomization to relapse or death, whichever occurred first
Measured: Up to 3 years
Overall survival (OS)
Overall Survival (OS) is defined as the time from the date of randomization to the date of documented death from any cause
Measured: Up to 5 years
Incidence of Adverse Events
For each of the AEs due to the following study treatment, the frequency of cases with the worst grade in all courses according to CTCAE v5.0 will be calculated using all treated patients as the denominator.
Measured: Up to 3 years
Treatment Completion Rate
This rate will be calculated for each eligible subject in accordance with the following equation. Treatment completion rate (%) = number of treatment courses completed/6 × 100
Measured: Up to 3 years

Timeline

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

1 Aug 2023Jun 2028

First posted20 Jul 2023
Study start1 Aug 2023
Primary completionJun 2026 (estimated)
Study completionJun 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for High-risk Stage II Colorectal CancerStudies of the same condition, open and under way.
More trials run by Fudan 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 340 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05954078
Sponsor's protocol ID: FINE Trial
Status last verified: May 2024
First submitted: 12 Jul 2023
Last updated: 20 May 2024
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Interested in taking part?

Each site lists its own contact. Pick the site nearest to you.

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?

See sites and contacts

Recruiting
Researching the Effect of Exercise on Cancer
Breast Cancer, Prostate Cancer
Active, not recruitingPhase 3
Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer
Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma
Active, not recruitingPhase 2
A Phase II Clinical Trial Comparing the Efficacy of RO7198457 Versus Watchful Waiting in Patients With ctDNA-positive, Resected Stage II (High Risk) and Stage III Colorectal Cancer
Colorectal Cancer Stage II, Colorectal Cancer Stage III
Active, not recruitingPhase 2
Therapy Adapted for High Risk and Low Risk HIV-Associated Anal Cancer
AIDS-Related Anal Carcinoma, Anal Margin Squamous Cell Carcinoma
RecruitingPhase 2
Immunotherapy (Toripalimab) for Reducing Recurrence Risk After Surgery for Mismatch Repair Deficient Stage IIB, IIC, or III Colon Cancer
Localized Colon Carcinoma, Stage IIB Colon Cancer AJCC v8

All High-risk Stage II Colorectal Cancer trials

Study at a glance

From the registry record, last updated by the sponsor on 20 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Circulating Tumor DNA Methylation Guided Postoperative Adjuvant Chemotherapy for High-risk Stage II/III Colorectal Cancer: A Multicenter, Prospective, Randomized Controlled Cohort Study (FINE Trial)
ClinicalTrials.gov ID: NCT05954078
Acronym / sponsor ID: FINE Trial
Conditions: High-risk Stage II Colorectal Cancer, Stage III Colorectal Cancer, Circulating Tumor DNA Methylation
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 340 participants (estimated)
Lead sponsor: Fudan UniversityUniversity, hospital or other
Study start: 1 Aug 2023 (actual)
Primary completion: Jun 2026 (estimated)
Study completion: Jun 2028 (estimated)
First posted: 20 Jul 2023 (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.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
mFOLFIRINOX adjuvant chemotherapy	Experimental	Drug: mFOLFIRINOX adjuvant chemotherapyPatients will receive mFOLFIRINOX once every two weeks for 6 cycles as adjuvant chemotherapy, after which a blood test is conducted to check the status of ctDNA. If the ctDNA remains positive, the treatment continues for another 6 cycles. If the ctDNA becomes negative, then maintenance chemotherapy with single-agent capecitabine is given once every 21 days for 4 cycles.
mFOLFOX6/XELOX adjuvant chemotherapy	Active comparator	Drug: mFOLFOX6/XELOX adjuvant chemotherapyPatients will receive mFOLFOX6 once every two weeks for 6 cycles or XELOX once every three weeks for 4 cycles as adjuvant chemotherapy. After the treatment, a blood test is conducted to check the status of ctDNA. If the ctDNA remains positive, the treatment continues with another 6 cycles of mFOLFOX 6 or 4 cycles of XELOX given once every 21 days. If the ctDNA becomes negative, then maintenance chemotherapy with single-agent capecitabine is given once every 21 days for 4 cycles.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Patients who have been histopathologically diagnosed with colorectal adenocarcinoma;
Patients who have undergone radical curative resection of the primary tumors;
Patients with CRC of high-risk stage II and stage III based on final findings (UICC TNM Classification, 8th Edition);
Patients who tested positive for ctDNA methylation at 5-7 days after surgery prior to enrollment;
Patients with no obvious relapse confirmed by chest, abdominal, and pelvic CT scans, etc.;

Key exclusion criteria (9 listed)

Neoadjuvant therapy performed before operation;
Blood transfusion performed during operation or within 2 weeks before operation;
Incomplete baseline samples, including preoperative plasma samples and plasma samples 5-7 days after operation;
Pregnant or lactating women who have fertility and do not take adequate contraceptive measures;
Have a history of other malignant tumors within 5 years, except cured cervical carcinoma in situ or non melanoma skin cancer;

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
mFOLFIRINOX adjuvant chemotherapyAlso: Oxaliplatin, Irinotecan, Leucovorin, 5-FluorouracilmFOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan 180 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 6 cycles	Drug	mFOLFIRINOX adjuvant chemotherapy
mFOLFOX6/XELOX adjuvant chemotherapyAlso: Oxaliplatin, Leucovorin, 5-FluorouracilmFOLFOX6 (oxaliplatin 85 mg/m2, and folinic acid 400 mg/m2 followed by 5-fluorouracil 400mg/m2 infusion, and 2400mg/m2 as a 46-hour continuous infusion on day 1) for 12 cycles or XELOX (oxaliplatin 130mg/m2, ivgtt, Q3w; capecitabine 1000mg/m2, p.o, Q3w) for 8 cycles	Drug	mFOLFOX6/XELOX adjuvant chemotherapy

Primary outcome

ctDNA clearance rate
Time frame: ctDNA clearance rate after 3 months of chemotherapy (6 cycles or 4 cycles for chemotherapy); ctDNA clearance rate after 6 months of chemotherapy (12 cycles or 8 cycles for chemotherapy)
The rate of ctDNA positive before chemotherapy that turns negative after adjuvant chemotherapy

4 secondary outcomes

Disease-free survival (DFS)
Time frame: Up to 3 years
Overall survival (OS)
Time frame: Up to 5 years
Incidence of Adverse Events
Time frame: Up to 3 years
Treatment Completion Rate
Time frame: Up to 3 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 20 May 2024.
Individual participant dataSharing planned: No

Related trials for High-risk Stage II Colorectal Cancer

Recruiting
Researching the Effect of Exercise on Cancer
Breast Cancer, Prostate Cancer
Active, not recruitingPhase 3
Nivolumab After Combined Modality Therapy in Treating Patients With High Risk Stage II-IIIB Anal Cancer
Anal Basaloid Carcinoma, Anal Canal Cloacogenic Carcinoma
Active, not recruitingPhase 2
A Phase II Clinical Trial Comparing the Efficacy of RO7198457 Versus Watchful Waiting in Patients With ctDNA-positive, Resected Stage II (High Risk) and Stage III Colorectal Cancer
Colorectal Cancer Stage II, Colorectal Cancer Stage III
Active, not recruitingPhase 2
Therapy Adapted for High Risk and Low Risk HIV-Associated Anal Cancer
AIDS-Related Anal Carcinoma, Anal Margin Squamous Cell Carcinoma
RecruitingPhase 2
Immunotherapy (Toripalimab) for Reducing Recurrence Risk After Surgery for Mismatch Repair Deficient Stage IIB, IIC, or III Colon Cancer
Localized Colon Carcinoma, Stage IIB Colon Cancer AJCC v8

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.

Fudan University Shanghai Cancer Center

Shanghai, China

86-18017317122

pengjj67@hotmail.com

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

Questions about this trial

What is this clinical trial studying?

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 11 inclusion and 9 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 20 May 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

ctDNA clearance rate (time frame: ctDNA clearance rate after 3 months of chemotherapy (6 cycles or 4 cycles for chemotherapy); ctDNA clearance rate after 6 months of chemotherapy (12 cycles or 8 cycles for 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 NCT05954078.

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 20 May 2024.