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

NCT06547203 | Recruiting Phase 2

• 1 other identifier: CITRUS
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer Metastatic

Keywords

Metastatic colorectal cancer; RAS/BRAF wild type; Right-sided; Cetuximab; PD-1 inhibitor

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  The proportion of patients who have achieved partial response (PR) plus complete response (CR), as assessed by the investigator using RECIST v1.1 criteria

  Assessed after every 4 cycles (each cycle is 14 days) for up to 24 months

Secondary Outcomes (5)

• Disease Control Rate

  Assessed after every 4 cycles (each cycle is 14 days) for up to 24 months

• Duration of Response

  Assessed after every 4 cycles (each cycle is 14 days) for up to 24 months

• Progression-Free Survival

  Assessed up to 24 months

• Overall Survival

  Assessed throughout the study duration (5 years)

• Adverse events (Treatment-related)

  Assessed throughout the study duration (5 years)

Study Arms (1)

Cetuimab plus toripalimab and irinotecan

EXPERIMENTAL

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.

Drug: Cetuximab; Drug: Toripalimab; Drug: Irinotecan

Interventions

Cetuximab DRUG

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

Also known as: Erbitux

Cetuimab plus toripalimab and irinotecan

Toripalimab DRUG

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

Also known as: Loqtorzi

Cetuimab plus toripalimab and irinotecan

Irinotecan DRUG

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

Also known as: CPT-11

Cetuimab plus toripalimab and irinotecan

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; toripalimab; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Central Study Contacts

Yuhong Li, PhD

CONTACT

87342487; liyh@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 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.

Study Record Dates

• First Submitted: July 18, 2024
• First Posted: August 9, 2024
• Study Start: July 18, 2024
• Primary Completion (Estimated): July 30, 2026
• Study Completion (Estimated): July 30, 2029
• Last Updated: August 9, 2024

Record last verified: 2024-08

Locations

CN (1)