RAS MutationPhase 2NCT06321081
ICE Study: Combination of Irinotecan Plus Cetuximab and Envafolimab as a Rechallenge Regimen in mCRC
A Phase 2 study testing irinotecan, cetuximab, envafolimab in people with RAS Mutation and Metastatic Colorectal Cancer, run by Beijing Hospital at 1 site in China.
Trial summary
This is a non-profit phase II, open, clinical study of the combination of irinotecan plus cetuximab and envafolimab as a rechallenge regimen, in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients (according to liquid biopsy at baseline). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- RAS Mutation, Metastatic Colorectal Cancer, MSS
- What is being tested?
- irinotecan, cetuximab, envafolimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2024to 30 Dec 2026
- 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 written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management.
- Male or female subjects aged ≥ 18 years. Histologically proven diagnosis of colorectal adenocarcinoma. Diagnosis of metastatic disease. RAS (NRAS and KRAS exon 2,3 and 4) and BRAF wild-type in liquid biopsy at screening (according to NGS) Efficacy of any front-line therapies containing cetuximab or irinotecan with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1)..
- More than 2 months since the last dose of cetuximab administered in first line treatment before randomization.
- Measurable disease according to RECIST criteria v1.1. ECOG PS of 0 to 1 at trial entry. Estimated life expectancy of more than 12 weeks. Adequate hematological function defined by white blood cell (WBC) count ≥ 2.5 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused).
- Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all subjects or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
- Adequate renal function defined by an estimated creatinine clearance > 30 mL/min according to the Cockcroft-Gault formula (or local institutional standard method).
- Effective contraception for both male and female subjects throughout the study and for at least 2 months after last study treatment administration if the risk of conception exists (Note: The effects of the trial drug on the developing human fetus are unknown; thus, women of childbearing potential and men must agree to use effective contraception, defined as 2 barrier methods, or 1 barrier method with a spermicide, an intrauterine device, or use of oral female contraceptive. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this trial, the treating physician should be informed immediately).
Who cannot join
- Any contraindication to cetuximab and/or envafolimab. Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix.
- Pregnancy. Breastfeeding. Participation in a clinical study or experimental drug treatment within 30 days before enrollment.
- Subjects receiving immunosuppressive agents (such as steroids) for any reason, should be tapered off these drugs before initiation of the trial treatment, with the exception of:
- Subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily Intranasal, inhaled, topical steroids, Local steroid injection (e.g., intra-articular injection) Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) No ongoing neurological symptoms related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) Prior organ transplantation, including allogeneic stemcell transplantation
- Significant acute or chronic infections including, among others:
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
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- Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent:
- Subjects with diabetes type I, vitiligo, psoriasis, hypo- or hyperthyroid disease not requiring immunosuppressive treatment are eligible.
- Subjects requiring hormone replacement with corticosteroids are eligible if steroids are administered only for the purpose of hormonal replacement and at doses ≤ 10 mg or equivalent prednisone per day.
- Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) are acceptable.
- Active infection requiring systemic therapy. Previous or ongoing administration of systemic steroids for the management of an acute allergic phenomenon is acceptable as long as it is anticipated that the administration of steroids will be completed in 14 days, or that the daily dose after 14 days will be ≤ 10 mg per day of equivalent prednisone.
- Known severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v 5 Grade ≥ 3), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma).
- History of hypersensitivity to Polysorbate 80 that led to unacceptable toxicity requiring treatment cessation.
- Persisting toxicity related to prior therapy of Grade > 1 NCI- CTCAE v 5.0. Known alcohol or drug abuse. Clinically significant (that is active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication.
- History of keratitis, ulcerative keratitis or severe dry eye. Since contact lent use is also a risk factor for keratitis and ulceration, it is not recommended.
- Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
- Legal incapacity or limited legal capacity.
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
Beijing Hospital
Beijing, Beijing Municipality, 100730
Yingying Huang, 86-10-85136715, yinghh@hotmail.com
About this study
Official title: ICE Study: a Clinical Study of the Combination of Irinotecan Plus Cetuximab and Envafolimab as a Rechallenge Regimen in mCRC
This is a non-profit phase II, open, clinical study of the combination of irinotecan plus cetuximab and envafolimab as a rechallenge regimen, in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients (according to liquid biopsy at baseline). Patients have been treated in front lines with irinotecan and cetuximab and had a clinical benefit (complete or partial response) from both of them, no matter whether they had treated by any PD-1 inhibitor before.
Read the detailed description
This is a non-profit phase II, open-label, clinical study of the combination irinotecan plus cetuximab and envafolimab as a rechallenge regimen, in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients (according to liquid biopsy at baseline). Patients have been treated in front lines with irinotecan and cetuximab and had a clinical benefit (complete or partial response) from both of them, no matter whether they had treated by any PD-1 inhibitor before.
30 patients will be treated with irinotecan plus cetuximab and envafolimab. For each patient, before treatment, a blood sample will be obtained and analyzed for circulating free tumorDNA, to identify RAS/BRAF wild type patient to be enrolled.
The same procedure will be performed at progression of the disease. Treatment will continue until:
disease progression. significant clinical deterioration any criterion for withdrawal from the trial or trial drug is fulfilled treatment may continue past the initial determination of disease progression according to RECIST 1.1. if the subject's performance status has remained stable, and if in the opinion of the Investigator, the subject will benefit from continued treatment and if other criteria are fulfilled as outlined in the protocol, that is, no new symptoms or worsening of existing symptoms and no decrease in performance score.
- Conditions
- RAS Mutation, Metastatic Colorectal Cancer, MSS
- Being tested
- irinotecan, cetuximab, 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.
irinotecan, cetuximab, envafolimabDrug
Also called CPT-11, PD-L1 inhibitor
rechallenge treatment
| Study group | Role | What they receive |
|---|---|---|
| ICE treatment group | Experimental | any RAS wild type mCRC patients who had got benefits from cetuximab or irinotecan will be treated with ICE regimen (Irinotecan 150mg/m2,Q2W, cetuximab 500mg/m2, Q2W, envafolimab 200mg, Q2w) Receives: Drug: irinotecan, cetuximab, envafolimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression free survival
the interval from enrollment to disease progression
Measured: from screening up to 36 months (from the start of therapy until disease progression or death due to any cause
Secondary outcomes (1)
Overal survival
the interval from enrollment to death for every cause.
Measured: from screening up to 36 months (from the start of therapy until death due to any cause
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2024
- Study start1 Mar 2024
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for RAS MutationStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beijing Hospital
- Sponsor type
- Other government
- Collaborators
- Bethune Charitable Foundation
- Responsible party
- Principal investigator, Yingying Huang, Beijing Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06321081
- Sponsor's protocol ID
- 2023BJYYEC-428-02
- Status last verified
- Jul 2026
- First submitted
- 14 Mar 2024
- Last updated
- 28 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ICE Study: a Clinical Study of the Combination of Irinotecan Plus Cetuximab and Envafolimab as a Rechallenge Regimen in mCRC
- ClinicalTrials.gov ID
- NCT06321081
- Acronym / sponsor ID
- 2023BJYYEC-428-02
- Conditions
- RAS Mutation, Metastatic Colorectal Cancer, MSS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Beijing HospitalOther government
- Collaborators
- Bethune Charitable Foundation
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 20 Mar 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.
This is a non-profit phase II, open, clinical study of the combination of irinotecan plus cetuximab and envafolimab as a rechallenge regimen, in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients (according to liquid biopsy at baseline). Patients have been treated in front lines with irinotecan and cetuximab and had a clinical benefit (complete or partial response) from both of them, no matter whether they had treated by any PD-1 inhibitor before.
Detailed description
This is a non-profit phase II, open-label, clinical study of the combination irinotecan plus cetuximab and envafolimab as a rechallenge regimen, in pre-treated RAS/BRAF wild type metastatic colorectal cancer patients (according to liquid biopsy at baseline). Patients have been treated in front lines with irinotecan and cetuximab and had a clinical benefit (complete or partial response) from both of them, no matter whether they had treated by any PD-1 inhibitor before.
30 patients will be treated with irinotecan plus cetuximab and envafolimab. For each patient, before treatment, a blood sample will be obtained and analyzed for circulating free tumorDNA, to identify RAS/BRAF wild type patient to be enrolled.
The same procedure will be performed at progression of the disease. Treatment will continue until:
disease progression. significant clinical deterioration any criterion for withdrawal from the trial or trial drug is fulfilled treatment may continue past the initial determination of disease progression according to RECIST 1.1. if the subject's performance status has remained stable, and if in the opinion of the Investigator, the subject will benefit from continued treatment and if other criteria are fulfilled as outlined in the protocol, that is, no new symptoms or worsening of existing symptoms and no decrease in performance score.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ICE treatment group | Experimental | Drug: irinotecan, cetuximab, envafolimabany RAS wild type mCRC patients who had got benefits from cetuximab or irinotecan will be treated with ICE regimen (Irinotecan 150mg/m2,Q2W, cetuximab 500mg/m2, Q2W, envafolimab 200mg, Q2w) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Signed written informed consent before any trial-related procedure is undertaken that is not part of the standard patient management.
- Male or female subjects aged ≥ 18 years. Histologically proven diagnosis of colorectal adenocarcinoma. Diagnosis of metastatic disease. RAS (NRAS and KRAS exon 2,3 and 4) and BRAF wild-type in liquid biopsy at screening (according to NGS) Efficacy of any front-line therapies containing cetuximab or irinotecan with a major response achieved (i.e. complete or partial response according to RECIST criteria v1.1)..
- More than 2 months since the last dose of cetuximab administered in first line treatment before randomization.
- Measurable disease according to RECIST criteria v1.1. ECOG PS of 0 to 1 at trial entry. Estimated life expectancy of more than 12 weeks. Adequate hematological function defined by white blood cell (WBC) count ≥ 2.5 × 109/L with absolute neutrophil count (ANC) ≥ 1.5 × 109/L, lymphocyte count ≥ 0.5 × 109/L, platelet count ≥ 100 × 109/L, and hemoglobin ≥ 9 g/dL (may have been transfused).
- Adequate hepatic function defined by a total bilirubin level ≤ 1.5 × the upper limit of normal (ULN) range and AST and alanine aminotransferase (ALT) levels ≤ 2.5 × ULN for all subjects or AST and ALT levels ≤ 5 x ULN (for subjects with documented metastatic disease to the liver).
Key exclusion criteria (17 listed)
- Any contraindication to cetuximab and/or envafolimab. Past or current history of malignancies other than colorectal carcinoma, except for curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix.
- Pregnancy. Breastfeeding. Participation in a clinical study or experimental drug treatment within 30 days before enrollment.
- Subjects receiving immunosuppressive agents (such as steroids) for any reason, should be tapered off these drugs before initiation of the trial treatment, with the exception of:
- Subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement dose, equivalent to ≤ 10 mg prednisone daily Intranasal, inhaled, topical steroids, Local steroid injection (e.g., intra-articular injection) Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) No ongoing neurological symptoms related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) Prior organ transplantation, including allogeneic stemcell transplantation
- Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome
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 |
|---|---|---|
| irinotecan, cetuximab, envafolimabAlso: CPT-11, PD-L1 inhibitorrechallenge treatment | Drug | ICE treatment group |
Primary outcome
progression free survival
Time frame: from screening up to 36 months (from the start of therapy until disease progression or death due to any cause
the interval from enrollment to disease progression
1 secondary outcome
Overal survival
Time frame: from screening up to 36 months (from the start of therapy until death due to any cause
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 28 Jul 2026.
- Individual participant dataSharing planned: Undecided
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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 Phase 2 study testing irinotecan, cetuximab, envafolimab in people with RAS Mutation and Metastatic Colorectal Cancer, run by Beijing Hospital 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 7 inclusion and 17 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 28 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 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 Yingying Huang (86 010 85136715, yinghh@hotmail.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: from screening up to 36 months (from the start of therapy until disease progression or death due to any cause). 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 28 Jul 2026.