Cetuximab, Irinotecan, Toripalimab in RAS/BRAF Wild-type Ultraselected Right-sided Colorectal Cancer Study

NCT ID: NCT06547203

Last Updated: 2024-08-09

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-18
• Study Completion Date: 2029-07-30

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.

Conditions

Colorectal Cancer Metastatic

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cetuimab plus toripalimab and irinotecan

Single Arm study, with patients receiving:

Cetuximab: 500 mg/m², intravenous infusion, once every 2 weeks. Toripalimab: 3 mg/kg, intravenous infusion, once every 2 weeks. Irinotecan: 150 mg/m², intravenous infusion, once every 2 weeks.

Patients will continue treatment until any of the following conditions occur: the researcher determines there is no longer a clinical benefit, intolerable toxicity occurs, a new anti-tumor treatment is initiated, withdrawal of informed consent, loss to follow-up, death, or other conditions specified in the protocol requiring termination of treatment.

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

Cetuximab: 500 mg/m², intravenous infusion, once every 2 weeks

Toripalimab

Intervention Type: DRUG

Toripalimab: 3 mg/kg, intravenous infusion, once every 2 weeks.

Irinotecan

Intervention Type: DRUG

Irinotecan: 150 mg/m², intravenous infusion, once every 2 weeks.

Interventions

Cetuximab

Cetuximab: 500 mg/m², intravenous infusion, once every 2 weeks

Intervention Type: DRUG

Toripalimab

Toripalimab: 3 mg/kg, intravenous infusion, once every 2 weeks.

Intervention Type: DRUG

Irinotecan

Irinotecan: 150 mg/m², intravenous infusion, once every 2 weeks.

Intervention Type: DRUG

Other Intervention Names

Erbitux; Loqtorzi; CPT-11

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sun Yat-sen University

OTHER

Sponsor Role: lead

Responsible Party

Yuhong Li

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yuhong Li, PhD

Role: CONTACT

liyh@sysucc.org.cn

87342487 ext. 020

Facility Contacts

Li Yuhong, MD

Role: primary

liyh@sysucc.org.cn

020-87342487

Other Identifiers

CITRUS

Identifier Type: -

Identifier Source: org_study_id