A Clinical Study to Evaluate the Efficacy and Safety of Envafolimab Combined With Cetuxima-βand mFOLFOX6 in Patients With MSS, RAS/BRAF Wild-Type Metastatic Colorectal Cancer (mCRC)

April 28, 2025 updated by: Rui-hua Xu, MD, PhD, Sun Yat-sen University

mFOLFOX and Cetuximab - β With or Without Envafolimab for MSS, RAS/BRAF Wild - Type Advanced Unresectable CRC: Prospective, Randomized, Controlled Phase Ⅱ/Ⅲ Trial

This is a prospective randomized controlled Phase Ⅱ/Ⅲ Clinical study to evaluate the clinical efficacy and safety of Envafolimab combining with Cetuximab -β and mFOLFOX6 in Patients With MSS, RAS/BRAF Wild-Type Metastatic Colorectal Cancer (mCRC)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Patients diagnosed with unresectable, microsatellite - stable (MSS), RAS/BRAF wild - type metastatic colorectal adenocarcinoma who have not received prior systemic anti-neoplastic therapy for metastatic or recurrent lesions will be included in this study.

In the Phase II study, approximately 186 patients will be enrolled, with 93 assigned to the experimental group and 93 to the control group. In the Phase III study, around 404 patients will be recruited, with 202 allocated to the experimental group and 202 to the control group.

Eligible patients will undergo a screening period of up to 28 days, followed by a treatment period consisting of 2 - week cycles for a maximum duration of 2 years. Subsequently, a follow - up period will be implemented, which includes a safety follow - up and survival follow - ups conducted every 12 weeks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
590

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510075
        • Medical Oncology,Sun Yat-sen University Cancer Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients are eligible for the study if they meet all of the following criteria:

    1. Prior to enrollment, the participant is required to sign a written informed consent form.
    2. Participants should be above 18 years，regardless of gender.
    3. Histopathologically confirmed untreated advanced colorectal adenocarcinoma.
    4. Tumors with RAS (KRAS, NRAS, HRAS) and BRAF wild-type, MSS phenotype, excluding appendiceal or anal cancer. All listed codons must be wild-type: KRAS: Exons 2, 3, 4 (Codons 12, 13, 59, 61, 117, 146) ; NRAS: Exons 2, 3, 4 (Codons 12, 13, 59, 61, 117, 146)
    5. Imaging (enhanced CT/MRI/PET-CT) confirms advanced/metastatic colorectal cancer with measurable lesions according to RECIST v1.1.
    6. No prior systemic therapy for advanced/metastatic colorectal cancer, including chemotherapy, EGFR inhibitors (cetuximab, panitumumab), VEGF inhibitors (bevacizumab), and immune checkpoint inhibitors (anti-PD-1/PD-L1/CTLA-4). Adjuvant/neoadjuvant chemotherapy within 6 months before recurrence/metastasis is considered first-line therapy.
    7. ECOG PS score 0-1.
    8. Expected survival >12 weeks.

    9. Adequate organ function (without blood component or growth factor use within 14 days):

      Hematology:Neutrophils ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L. Liver/kidney function: SCr ≤1.5×ULN or creatinine clearance ≥50 ml/min, TBIL ≤1.5×ULN, AST/ALT ≤2.5×ULN (≤5×ULN if due to liver metastasis), urine protein <2+ (≤1g/24h if ≥2+).

    10. Normal coagulation, no active bleeding/thrombosis: INR ≤1.5×ULN, APTT ≤1.5×ULN, PT ≤1.5×ULN.
    11. Non-surgically sterile women of childbearing potential must use contraception during and 3 months after treatment; serum/urine HCG negative within 7 days before enrollment; not breastfeeding. Non-surgically sterile men must use contraception with partners during and 3 months after treatment.

    12. Willing participant with good compliance for safety and survival follow-up.

      Exclusion Criteria:

      -

  • Patients will be excluded from the study if they meet any of the following exclusion criteria:

    1. Other malignancies in the past or current (excluding cured basal cell carcinoma or cervical carcinoma in situ).
    2. Current duodenal ulcer, ulcerative colitis, intestinal obstruction, or other GI conditions that may cause bleeding or perforation, as judged by the investigator.
    3. Patients with symptomatic pleural, peritoneal, or pericardial effusions requiring treatment.
    4. History of allergy to monoclonal proteins or any component of the study drugs.
    5. Oral traditional Chinese medicine, immunomodulators within 2 weeks, or radiotherapy within 4 weeks before treatment.
    6. Thyroid dysfunction that is uncontrolled by medication.
    7. Uncontrolled hypertension despite receiving optimal treatment (systolic BP>150 mmHg or diastolic BP>90 mmHg).
    8. Uncontrolled cardiac conditions: (1) NYHA Class II+ heart failure; (2) unstable angina; (3) myocardial infarction within 1 year; (4) clinically significant arrhythmias requiring treatment.
    9. Active autoimmune disease or a history of such diseases.
    10. Immunosuppressants, systemic, or absorbable topical steroids for immunosuppression (>10 mg/day prednisone or equivalent) within 2 weeks before enrollment.
    11. CNS metastases.
    12. Active infection or unexplained fever>38.5°C during screening or before first dose (tumor-related fever is acceptable).
    13. History or current evidence of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonia, or severe pulmonary dysfunction.
    14. Congenital or acquired immunodeficiency, such as HIV infection, or active hepatitis (elevated transaminases not meeting inclusion criteria, HBV DNA≥1000 IU/ml, HCV RNA≥1000 IU/ml).
    15. Live vaccine administration within 4 weeks before first dose or planned during the study.
    16. History of psychiatric drug abuse, alcoholism, or drug addiction.
    17. Pregnant or breastfeeding women, or those planning pregnancy during the trial.
    18. Any other factor that may lead to premature study discontinuation, as judged by the investigator.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Envafolimab combining with Cetuximab -β and mFOLFOX6
Drug: Cetuxima-β
500 mg/m², initial intravenous infusion (IV)>120 min, subsequent IV >60 min , D1，every 2 weeks
Drug: Envafolimab
a single fixed dose of 200 mg, subcutaneous injection(SC), every 2 weeks (Day 1 of each cycle [D1])
Drug: mFOLFOX6
Oxaliplatin 85 mg/m² , IV, over 120 min, Day 1; Leucovorin 400 mg/m² (or Calcium Folinate 200 mg/m²), IV, over 120 min, D1; 5-FU 400 mg/m² , bolus injection, followed by 1200 mg/(m²·d) continuous IV for 2 days (total dose 2400 mg/m² over 46 - 48 hours)
Active Comparator: Cetuximab -β and mFOLFOX6
Drug: Cetuxima-β
500 mg/m², initial intravenous infusion (IV)>120 min, subsequent IV >60 min , D1，every 2 weeks
Drug: mFOLFOX6
Oxaliplatin 85 mg/m² , IV, over 120 min, Day 1; Leucovorin 400 mg/m² (or Calcium Folinate 200 mg/m²), IV, over 120 min, D1; 5-FU 400 mg/m² , bolus injection, followed by 1200 mg/(m²·d) continuous IV for 2 days (total dose 2400 mg/m² over 46 - 48 hours)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Progressin Free Survival，PFS
Time Frame: Time Frame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 3 years
Progression-free survival based on RECIST v1.1
Time Frame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
OS，Overall survival
Time Frame: from the date of first dose unitl the date of death from any cause，assessed up to 3 years
from the date of first dose unitl the date of death from any cause，assessed up to 3 years
ORR， Objective response
Time Frame: up to 3 years
Objective response rate based on RECIST v1.1
up to 3 years
DCR， Disease control rate
Time Frame: up to 1 year
the proportion of patients with the best overall response of CR, PR, or stable disease (SD)
up to 1 year
NED Rate， No Evidence of Disease Rate
Time Frame: up to 3 years
The proportion of participants with no evidence of disease after treatment, as determined by current assessments (pathological, imaging, and molecular biology). NED includes complete response (CR), R0 resection, or other local treatments, such as radiofrequency, microwave, or cryoablation (which can be combined with surgery), that eliminate the tumor.
up to 3 years
Safety(Adverse Event (AE) Incidence)
Time Frame: up to 3 years
Adverse Event (AE) Incidence
up to 3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 28, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2025

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 6, 2025

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 6, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • SMA CRC 005

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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