Clinical trial NCT06547203: Cetuximab, Irinotecan, Toripalimab in RAS/BRAF Wild-type Ultraselected Right-sided Colorectal Cancer Study
Official title: Negative Ultraselection of Patients With RAS/BRAF Wild-type Refractory Right-Sided Metastatic Colorectal Cancer Receiving Cetuximab in Combination With Toripalimab and Irinotecan: A Phase II, Single-arm Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Colorectal Cancer Metastatic
Keywords: Metastatic colorectal cancer
RAS/BRAF wild type
Right-sided
Cetuximab
PD-1 inhibitor
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2024-08-09
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: Assessed after every 4 cycles (each cycle is 14 days) for up to 24 months
Secondary outcomes:
measure: Disease Control Rate
timeFrame: Assessed after every 4 cycles (each cycle is 14 days) for up to 24 months
measure: Duration of Response
timeFrame: Assessed after every 4 cycles (each cycle is 14 days) for up to 24 months
measure: Progression-Free Survival
timeFrame: Assessed up to 24 months
measure: Overall Survival
timeFrame: Assessed throughout the study duration (5 years)
measure: Adverse events (Treatment-related)
timeFrame: Assessed throughout the study duration (5 years)
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
References: