Colorectal Cancer Metastatic
Conditions
Keywords
Metastatic colorectal cancer, RAS/BRAF wild type, Right-sided, Cetuximab, PD-1 inhibitor
Brief summary
The objective of this clinical trial is to evaluate the efficacy and safety of cetuximab combined with PD-1 inhibitor and irinotecan in negative ultraselection RAS/BRAF wild-type refractory right-sided metastatic colorectal cancer.
Detailed description
The present study focuses on exploring the effectiveness and safety of cetuximab combined with a PD-1 inhibitor and irinotecan in treating refractory, right-sided metastatic colorectal cancer (mCRC) patients who are negative ultraselected for RAS/BRAF mutations. Colorectal cancer ranks among the most prevalent digestive malignancies globally, with right-sided mCRC generally exhibiting poorer outcomes than left-sided cases. Current treatment guidelines vary based on genetic mutations and tumor location, recommending cetuximab for left-sided RAS/BRAF wild-type mCRC and alternative therapies for right-sided or mutated cases. Despite limited clinical data on EGFR inhibitors for right-sided mCRC, retrospective analyses suggest varying efficacy outcomes. The study aims to address these gaps by investigating cetuximab and PD-1 inhibitor combination therapy in this specific patient population, potentially enhancing treatment options for refractory mCRC.
Interventions
DRUGCetuximab
Cetuximab: 500 mg/m², intravenous infusion, once every 2 weeks
DRUGToripalimab
Toripalimab: 3 mg/kg, intravenous infusion, once every 2 weeks.
DRUGIrinotecan
Irinotecan: 150 mg/m², intravenous infusion, once every 2 weeks.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
To investigate the objective response rate (ORR) of cetuximab combined with toripalimab and irinotecan in right-sided mCRC patients with negative ultraselected RAS/BRAF wild-type who have progressed after previous treatments with bevacizumab, irinotecan, oxaliplatin, and 5-fluorouracil.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed colorectal adenocarcinoma. * Primary tumor located in the right colon. * Metastatic disease with at least one measurable lesion according to RECIST v1.1 criteria. * Histologically tested as RAS/BRAF V600E wild-type and negative ultraselected for mutations including: RAS/BRAF V600E/PIK3CA/PTEN/EGFR (ECD), HER2 and MET amplification, and ALK/RET/NTRK1 gene fusions. * Patients who have progressed after previous treatments including bevacizumab, irinotecan, oxaliplatin, and 5-fluorouracil, with tumor progression occurring during or within 3 months after irinotecan treatment. * No prior treatment with anti-EGFR or PD-1 antibodies. * Normal hematological function (platelets \>90×10\^9/L; white blood cells \>3×10\^9/L; neutrophils \>1.5×10\^9/L). * Serum bilirubin ≤1.5 times the upper limit of normal (ULN), transaminases ≤5 times ULN. * No ascites, normal coagulation function, albumin ≥35 g/L. * Liver function classified as Child-Pugh grade A. * Serum creatinine less than ULN, or calculated creatinine clearance \>50 ml/min (using the Cockcroft-Gault formula). * At least one measurable lesion according to RECIST v1.1 criteria. * ECOG performance status of 0-2. * Expected survival \>3 months. * Signed written informed consent. * Willing and able to undergo follow-up until death or study completion or termination.
Exclusion criteria
* Severe arterial thrombosis or ascites. * Bleeding tendencies or coagulation disorders. * Hypertensive crisis or hypertensive encephalopathy. * Severe uncontrolled systemic complications such as infections or diabetes. * Clinically significant cardiovascular diseases such as cerebrovascular accident (within 6 months prior to enrollment), myocardial infarction (within 6 months prior to enrollment), uncontrolled hypertension despite appropriate medication, unstable angina, congestive heart failure (NYHA grade 2-4), or arrhythmias requiring medication. * History of or physical examination showing central nervous system diseases (e.g., primary brain tumor, uncontrolled epilepsy, any history of brain metastasis or stroke). * Other malignancies within the past 5 years (except for basal cell carcinoma of the skin after curative surgery and/or carcinoma in situ of the cervix). * Use of immunosuppressive drugs within 1 week before treatment, excluding nasal, inhaled, or other topical steroids or physiological doses of systemic steroids (i.e., not exceeding 10 mg/day of prednisone or an equivalent dose of other steroids) or steroids used to prevent contrast agent allergies. * Steroid-dependent interstitial lung disease. * Known active autoimmune disease requiring symptomatic treatment or history of such disease within the past 2 years. Patients with vitiligo, psoriasis, alopecia, or -Graves' disease not requiring systemic treatment within the past 2 years, hypothyroidism requiring only thyroid hormone replacement, and type I diabetes requiring only insulin replacement can be enrolled. * Known history of primary immunodeficiency. * Known active tuberculosis. * Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. * Receipt of any investigational drug treatment within the last 28 days before the study. * Allergy to any drugs in the study. * Pregnant or breastfeeding women. * Women of childbearing potential (within 2 years of last menstruation) or men capable of fathering a child who are not using or refuse to use effective non-hormonal contraceptive methods (e.g., intrauterine device, barrier method combined with spermicide, or sterilization). * Inability or unwillingness to comply with the study protocol. * Presence of any other disease, functional impairment caused by metastatic lesions, or suspicious conditions found during a physical examination indicating a contraindication to the study drugs or high risk for treatment-related complications.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Assessed after every 4 cycles (each cycle is 14 days) for up to 24 months | The proportion of patients who have achieved partial response (PR) plus complete response (CR), as assessed by the investigator using RECIST v1.1 criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate | Assessed after every 4 cycles (each cycle is 14 days) for up to 24 months | The proportion of patients who have achieved complete response (CR), partial response (PR), or stable disease (SD) following treatment initiation. |
| Duration of Response | Assessed after every 4 cycles (each cycle is 14 days) for up to 24 months | Length of time from the initial detection of a measurable response (complete response or partial response) to the treatment until the first documentation of disease progression or recurrence |
| Progression-Free Survival | Assessed up to 24 months | The length of time from the start of treatment until the disease progresses or the patient dies from any cause, whichever occurs first. |
| Overall Survival | Assessed throughout the study duration (5 years) | Defined as the time from the start of study treatment to death due to any cause |
| Adverse events (Treatment-related) | Assessed throughout the study duration (5 years) | Assessment of adverse events and their severity according to NCI CTCAE version 5.0 criteria. |
Countries
China
Contacts
Primary ContactYuhong Li, PhD
Outcome results
None listed