Metastatic Colorectal CancerPhase 2CEILNCT05959356
Cetuximab and Envafolimab Plus mFOLFOXIRI as First-line Treatment for RAS/BRAF Wild-type, MSS, Unresectable Left-side Metastatic Colorectal Cancer
A Phase 2 study testing Cetuximab + Envafolimab + mFOLFOXIRI and Cetuximab + mFOLFOX6 in people with Metastatic Colorectal Cancer, run by Sun Yat-sen University at 3 sites in China.
Trial summary
The primary aim of phase II CEIL study is to evaluate the efficacy of cetuximab and envafolimab plus mFOLFOXIRI versus cetuximab plus mFOLFOX6 as first line treatment of patients with initially unresectable and previously untreated RAS/BRAF wild-type, MSS, left-side metastatic colorectal cancer(mCRC), in terms of… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Cetuximab + Envafolimab + mFOLFOXIRI and Cetuximab + mFOLFOX6
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 198 participants
- Where
- 3 sitesChina
- Study dates
- 9 Nov 2023to 31 Dec 2028
- Phase
- Phase 2
- 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
Who may be able to join
- Signed informed consent obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.
- Male or female subjects ≥ 18 years, expected lifespan ≥ 12 weeks.
- Patients have histologically or cytologically confirmed RAS and BRAF wild-type, MSS metastatic colorectal adenocarcinoma (mCRC), excluding appendiceal and anal cancers.
- AJCC/UICC stage IV left-side metastatic colorectal cancer. At least one measurable lesion according to RECIST 1.1.
- The patient has not previously received any systemic treatment specifically targeting advanced or metastatic colorectal cancer, including chemotherapy, monoclonal antibodies such as cetuximab or panitumumab targeting the epidermal growth factor receptor (EGFR), bevacizumab targeting the vascular endothelial growth factor (VEGF), immune checkpoint inhibitors such as anti-PD-1 or anti-PD-L1 antibodies, and anti-CTLA-4 antibodies. If recurrence or metastasis occurs during or within 6 months after adjuvant or neoadjuvant chemotherapy, adjuvant/neoadjuvant therapy is considered as a first-line systemic treatment for advanced or metastatic disease.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
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- Within 7 days before treatment, the following laboratory test values are obtained and appropriate organ function is present:
- Hemoglobin ≥ 90g/L, neutrophil count ≥ 1.5 × 10^9/L, platelet count ≥ 75 × 10^9/L; Serum total bilirubin ≤ 1.5 × upper limit of normal (UNL); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × UNL; if there are liver metastases, AST or ALT ≤ 5 × UNL; Serum creatinine ≤ 1.5 × UNL.
- Women of childbearing potential must have a negative blood pregnancy test at the baseline visit. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 continuous months, are surgically sterile, or are sexually inactive.
- Patients are not allowed to participate in other clinical trials during the study period and willing to comply with the study protocol and visit plan.
Who cannot join
- Concurrent active malignancy, excluding malignancies with disease-free survival of 5 years or more or in situ carcinoma considered cured after adequate treatment.
- Currently diagnosed with gastrointestinal diseases such as duodenal ulcer, ulcerative colitis, intestinal obstruction, or other conditions determined by the investigator to potentially cause gastrointestinal bleeding or perforation.
- Experienced thrombotic or embolic events, such as cerebrovascular accidents (including transient ischemic attacks), pulmonary embolism, or deep vein thrombosis, within the 12 months prior to study enrollment.
- Experienced the following conditions within the 12 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) class II or above heart failure, clinically significant supraventricular or ventricular arrhythmias, or symptomatic congestive heart failure.
- Use of systemic antibiotics for ≥7 days within the 4 weeks prior to study enrollment, or the occurrence of unexplained fever (>38.5°C) during the screening period/prior to the first dose (fever attributed to the tumor can be considered for enrollment, as determined by the investigator).
- Presence of uncontrolled pleural effusion, ascites, or pericardial effusion within 14 days prior to study enrollment despite appropriate treatment.
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- Presence of any unresolved adverse events of Grade 2 or higher (excluding anemia, alopecia, and skin pigmentation) attributed to previous treatments according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
- Presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, and acute pneumonia).
- Known human immunodeficiency virus (HIV) infection or known active hepatitis (defined as HBV-DNA ≥ 500 IU/ml for hepatitis B, and HCV-RNA above the limit of detection for hepatitis C) or co-infection with hepatitis B and C.
- History of known or suspected allergy to any investigational drug used in the study.
- Pregnancy or lactation in women.
- Pre-menopausal women (last menstrual period <2 years ago) who do not use or refuse to use effective non-hormonal contraception, or fertile men.
- Presence of other significant physical or mental illnesses or laboratory abnormalities that may increase the risk of participation in the study, interfere with study results, or are deemed unsuitable for participation by the investigator.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 recruiting
- Recruiting
The First People's Hospital of Foshan
Foshan, Guangdong, 528000
Wei Wang, Ph.D, 8618666392971
- Recruiting
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, 510655
Yanhong Deng, Ph.D, 8613925106525, dengyanh@mail.sysu.edu.cn
- Recruiting
Affiliated Cancer Hospital of Guizhou Medical University
Guiyang, Guizhou, 550000
Wen-Ling Wang, Ph.D, 8613885077539
About this study
Official title: Cetuximab and Envafolimab Plus mFOLFOXIRI Versus Cetuximab Plus mFOLFOX6 as First-line Treatment for RAS/BRAF Wild-type, MSS, Unresectable Left-side Metastatic Colorectal Cancer: A Randomized Controlled Phase II Trial (CEIL)
The primary aim of phase II CEIL study is to evaluate the efficacy of cetuximab and envafolimab plus mFOLFOXIRI versus cetuximab plus mFOLFOX6 as first line treatment of patients with initially unresectable and previously untreated RAS/BRAF wild-type, MSS, left-side metastatic colorectal cancer(mCRC), in terms of Progression-free Survival.
Read the detailed description
This is a prospective, open-label, multi-center, randomized controlled phase II trial in which patients with initially unresectable and previously untreated RAS/BRAF wild-type, MSS, left-side mCRC will be randomized to two therapy groups:
Experimental arm A: receive induction treatment with cetuximab and envafolimab plus mFOLFOXIRI up to 8 cycles followed by maintenance with cetuximab and envafolimab plus 5-FU/LV until disease progression, unacceptable toxicity or patient's refusal.
Standard arm B: receive induction treatment with cetuximab plus mFOLFOX6 up to 8 cycles followed by maintenance with cetuximab plus 5-FU/LV until disease progression, unacceptable toxicity or patient's refusal.
The second- and subsequent lines of treatment will be at investigators' choice.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Cetuximab + Envafolimab + mFOLFOXIRI, Cetuximab + mFOLFOX6
- Keywords
- First-line treatment, RAS/BRAF wild-type, Microsatellite stable(MSS), Unresectable left-side metastatic colorectal cancer, Envafolimab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cetuximab + Envafolimab + mFOLFOXIRIDrug
Also called Cetuximab or c225, Envafolimab, Irinotecan, Oxaliplatin
Cetuximab 500mg/m² + envafolimab 200mg + irinotecan 150 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of each 2 weeks cycle up to max 8 cycles, followed by maintenance with cetuximab 500mg/m² + envafolimab 200mg + leucovorin 200 mg/m² + 5-FU 400 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of each 2 weeks cycle until PD, unacceptable toxicity or patient's refusal.
Cetuximab + mFOLFOX6Drug
Also called Cetuximab or c225, Oxaliplatin, Leucovorin, 5-FU
Cetuximab 500mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 400 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of each 2 weeks cycle up to max 8 cycles, followed by maintenance with cetuximab 500mg/m² + leucovorin 200 mg/m² + 5-FU 400 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of each 2 weeks cycle until PD, unacceptable toxicity or patient's refusal.
| Study group | Role | What they receive |
|---|---|---|
| Arm A | Experimental | cetuximab+envafolimab+mFOLFOXIRI up to 8 cycles followed by maintenance with cetuximab+envafolimab+5-FU/LV Receives: Drug: Cetuximab + Envafolimab + mFOLFOXIRI |
| Arm B | Active comparator | cetuximab+mFOLFOX6 up to 8 cycles followed by maintenance with cetuximab+5-FU/LV Receives: Drug: Cetuximab + mFOLFOX6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.
Measured: 2 year
Secondary outcomes (7)
Objective response rate
CR + PR rate according to RECIST
Measured: 2 year
Disease control rate
CR + PR + SD rate according to RECIST
Measured: 2 year
No evidence of disease
The percentage of patients who had a curative treatment following protocol treatment, i.e., liver metastases that can be completely resected and/or ablated with no evidence of residual malignant disease.
Measured: 2 year
Overall survival
Time from date of randomization until the date of first documented death from any cause.
Measured: 4 year
Safety (Incidence of Adverse Events)
Percentage of patients, relative to the total of enrolled subjects, experiencing a specific adverse event of grade 3/4, according to National Cancer Institute Common Toxicity Criteria (version 5.0), during the induction and the maintenance phases of treatment.
Measured: 2 year
Health related quality of life
Scores according to EORTC QLQ-CR29 scoring manual.
Measured: Every 2 weeks after the first treatment until 6 months.
Quality-adjusted time without symptoms or toxicity
Q-TWiST was calculated as the sum of the utility-weighted mean durations for each health state. Q-TWiST = (TWiST × μTWiST) + (TOX × μTOX) + (REL × μREL).
Base case utilities: μTWiST = 1, μTOX = 0.5, μREL = 0.5. Duration of AEs was measured until disease progression. All time in TOX was front-loaded at the beginning of threrapy.
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2023
- Study start9 Nov 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 198 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yanhong Deng, Sun Yat-sen University
- Investigators
- Yanhong Deng, Ph.D, Principal investigator, Sixth Affiliated Hospital, Sun Yat-sen University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05959356
- Sponsor's protocol ID
- GIHSYSU-33
- Acronym
- CEIL
- Status last verified
- Nov 2025
- First submitted
- 16 Jul 2023
- Last updated
- 17 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cetuximab and Envafolimab Plus mFOLFOXIRI Versus Cetuximab Plus mFOLFOX6 as First-line Treatment for RAS/BRAF Wild-type, MSS, Unresectable Left-side Metastatic Colorectal Cancer: A Randomized Controlled Phase II Trial (CEIL)
- ClinicalTrials.gov ID
- NCT05959356
- Acronym / sponsor ID
- CEIL / GIHSYSU-33
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- First-line treatment, RAS/BRAF wild-type, Microsatellite stable(MSS), Unresectable left-side metastatic colorectal cancer, Envafolimab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 198 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 9 Nov 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 25 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.
The primary aim of phase II CEIL study is to evaluate the efficacy of cetuximab and envafolimab plus mFOLFOXIRI versus cetuximab plus mFOLFOX6 as first line treatment of patients with initially unresectable and previously untreated RAS/BRAF wild-type, MSS, left-side metastatic colorectal cancer(mCRC), in terms of Progression-free Survival.
Detailed description
This is a prospective, open-label, multi-center, randomized controlled phase II trial in which patients with initially unresectable and previously untreated RAS/BRAF wild-type, MSS, left-side mCRC will be randomized to two therapy groups:
Experimental arm A: receive induction treatment with cetuximab and envafolimab plus mFOLFOXIRI up to 8 cycles followed by maintenance with cetuximab and envafolimab plus 5-FU/LV until disease progression, unacceptable toxicity or patient's refusal.
Standard arm B: receive induction treatment with cetuximab plus mFOLFOX6 up to 8 cycles followed by maintenance with cetuximab plus 5-FU/LV until disease progression, unacceptable toxicity or patient's refusal.
The second- and subsequent lines of treatment will be at investigators' choice.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A | Experimental | Drug: Cetuximab + Envafolimab + mFOLFOXIRIcetuximab+envafolimab+mFOLFOXIRI up to 8 cycles followed by maintenance with cetuximab+envafolimab+5-FU/LV |
| Arm B | Active comparator | Drug: Cetuximab + mFOLFOX6cetuximab+mFOLFOX6 up to 8 cycles followed by maintenance with cetuximab+5-FU/LV |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Signed informed consent obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent.
- Male or female subjects ≥ 18 years, expected lifespan ≥ 12 weeks.
- Patients have histologically or cytologically confirmed RAS and BRAF wild-type, MSS metastatic colorectal adenocarcinoma (mCRC), excluding appendiceal and anal cancers.
- AJCC/UICC stage IV left-side metastatic colorectal cancer. At least one measurable lesion according to RECIST 1.1.
- The patient has not previously received any systemic treatment specifically targeting advanced or metastatic colorectal cancer, including chemotherapy, monoclonal antibodies such as cetuximab or panitumumab targeting the epidermal growth factor receptor (EGFR), bevacizumab targeting the vascular endothelial growth factor (VEGF), immune checkpoint inhibitors such as anti-PD-1 or anti-PD-L1 antibodies, and anti-CTLA-4 antibodies. If recurrence or metastasis occurs during or within 6 months after adjuvant or neoadjuvant chemotherapy, adjuvant/neoadjuvant therapy is considered as a first-line systemic treatment for advanced or metastatic disease.
Key exclusion criteria (13 listed)
- Concurrent active malignancy, excluding malignancies with disease-free survival of 5 years or more or in situ carcinoma considered cured after adequate treatment.
- Currently diagnosed with gastrointestinal diseases such as duodenal ulcer, ulcerative colitis, intestinal obstruction, or other conditions determined by the investigator to potentially cause gastrointestinal bleeding or perforation.
- Experienced thrombotic or embolic events, such as cerebrovascular accidents (including transient ischemic attacks), pulmonary embolism, or deep vein thrombosis, within the 12 months prior to study enrollment.
- Experienced the following conditions within the 12 months prior to study enrollment: myocardial infarction, severe/unstable angina pectoris, New York Heart Association (NYHA) class II or above heart failure, clinically significant supraventricular or ventricular arrhythmias, or symptomatic congestive heart failure.
- Use of systemic antibiotics for ≥7 days within the 4 weeks prior to study enrollment, or the occurrence of unexplained fever (>38.5°C) during the screening period/prior to the first dose (fever attributed to the tumor can be considered for enrollment, as determined by the investigator).
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 |
|---|---|---|
| Cetuximab + Envafolimab + mFOLFOXIRIAlso: Cetuximab or c225, Envafolimab, Irinotecan, OxaliplatinCetuximab 500mg/m² + envafolimab 200mg + irinotecan 150 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of each 2 weeks cycle up to max 8 cycles, followed by maintenance with cetuximab 500mg/m² + envafolimab 200mg + leucovorin 200 mg/m² + 5-FU 400 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of each 2 weeks cycle until PD, unacceptable toxicity or patient's refusal. | Drug | Arm A |
| Cetuximab + mFOLFOX6Also: Cetuximab or c225, Oxaliplatin, Leucovorin, 5-FUCetuximab 500mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 400 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of each 2 weeks cycle up to max 8 cycles, followed by maintenance with cetuximab 500mg/m² + leucovorin 200 mg/m² + 5-FU 400 mg/m² + 5-FU 2400 mg/m² civ. 46h all on day 1 of each 2 weeks cycle until PD, unacceptable toxicity or patient's refusal. | Drug | Arm B |
Primary outcome
Progression free survival
Time frame: 2 year
Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.
7 secondary outcomes
Objective response rate
Time frame: 2 year
Disease control rate
Time frame: 2 year
No evidence of disease
Time frame: 2 year
Overall survival
Time frame: 4 year
Safety (Incidence of Adverse Events)
Time frame: 2 year
Health related quality of life
Time frame: Every 2 weeks after the first treatment until 6 months.
Quality-adjusted time without symptoms or toxicity
Time frame: 2 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 17 Dec 2025.
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CRC
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.
Yanhong Deng, Ph.D principal investigator
Sixth Affiliated Hospital, Sun Yat-sen University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cetuximab + Envafolimab + mFOLFOXIRI and Cetuximab + mFOLFOX6 in people with Metastatic Colorectal Cancer, run by Sun Yat-sen University at 3 sites 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 10 inclusion and 13 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 17 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Yanhong Deng, Ph.D (86-13925106525, 13925106525@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: 2 year). 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 17 Dec 2025.