Cetuximab Plus FOLFOXIRI vs Cetuximab Plus FOLFOX For CRCLM

NCT03493048 | Active Not Recruiting Phase 2

• 1 other identifier: ERBIRINOX-CRCLM
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the trial is to optimize response rates and rates of secondary resections of metastases in patients with initially non-resectable metastatic colorectal cancer Liver Metastasis of RAS wildtype. The patients will be treated in two therapy groups: Experimental arm A: Chemotherapy with FOLFOXIRI + Cetuximab Standard arm B: Chemotherapy with FOLFOX + Cetuximab

Conditions

Colorectal Cancer; Liver Metastases

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Partial response (PR) plus complete response (CR)): assessed by the investigator using RECIST v1.1 criteria

  assessed up to 12 months

Secondary Outcomes (5)

• Depth of Response

  Each follow up visit, assessed up to 12 months

• R0 Resection Rate

  Each follow up visit, assessed up to 12 months

• Early Tumor Shrinkage

  Each follow up visit, assessed up to 12 months

• Progression-Free Survival

  Each follow up visit, assessed up to 60 months

• Overall Survival

  Each follow up visit, assessed up to 60 months

Study Arms (2)

Cetuximab Plus FOLFOXIRI

EXPERIMENTAL

Cetuximab Plus FOLFOXIRI Patients will receive Cetuximab Plus FOLFOXIRI every 14 days: Cetuximab 500mg/m2 ivd over 90 minutes on Day 1; Oxaliplatin 85 mg/m2 ivd over 3 hours on Day 1; Irinotecan 130 mg/m2 ivd over 90 minutes on Day 1; Leucovorin (l-LV) 200mg/m2 ivd over 2 hours on Day 1; followed by 5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion on Day 1.

Drug: Irinotecan; Drug: Cetuximab; Drug: 5-fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin

Cetuximab Plus FOLFOX

ACTIVE COMPARATOR

Patients will receive Cetuximab Plus FOLFOX every 14 days: Cetuximab 500mg/m2 ivd over 90 minutes on Day 1; Oxaliplatin 85 mg/m2 ivd over 3 hours on Day 1; Leucovorin (l-LV) 200mg/m2 ivd over 2 hours on Day 1; followed by 5-Fluorouracil 2.4 g/m2 for 46 hours continuous infusion on Day 1.

Drug: Cetuximab; Drug: 5-fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin

Interventions

Irinotecan DRUG

Irinotecan 130 mg/m²

Also known as: CPT-11

Cetuximab Plus FOLFOXIRI

Cetuximab DRUG

Cetuximab, iv, 500mg/m2

Also known as: Erbitux

Cetuximab Plus FOLFOX; Cetuximab Plus FOLFOXIRI

5-fluorouracil DRUG

5-FU 2400 mg/m² cont. inf.

Also known as: 5-FU

Cetuximab Plus FOLFOX; Cetuximab Plus FOLFOXIRI

Oxaliplatin DRUG

oxaliplatin 85 mg/m²

Also known as: L-OHP

Cetuximab Plus FOLFOX; Cetuximab Plus FOLFOXIRI

Leucovorin DRUG

leucovorin 200 mg/m²

Also known as: FOLINIC ACID

Cetuximab Plus FOLFOX; Cetuximab Plus FOLFOXIRI

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and ≤ 70 years.
• Histologically confirmed colorectal adenocarcinoma.
• Liver metastasis confirmed by imaging or pathology.
• The multidisciplinary team (MDT) determines that the liver metastases are unresectable, which is specifically defined as ① metastatic lesions ≥ 5; ② ineligible for R0 resection; ③ expected insufficient residual liver volume after resection; ④ unable to preserve all three hepatic veins after resection, unable to ensure that the blood flow and bile ducts of the residual liver into and out of the liver could be preserved, and unable to preserve the adjacent two liver segments. Patients who meet any of the above criteria can be determined as having initially unresectable liver metastases.
• Patients with wild-type RAS.
• No prior treatment for liver metastases, including chemotherapy, surgery, radiotherapy, transcatheter arterial chemoembolization (TACE), and targeted therapy.
• Absence of extrahepatic metastasis confirmed by CT, MRI or PET/CT (if necessary) (enrollment can be considered if there is a lung or lymph node lesion less than 10 mm, which is difficult to determine metastases).
• Normal hematologic function (platelets \> 90 × 109/L; leukocytes \> 3 × 109/L; neutrophils \> 1.5 × 109/L).
• Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN) and transaminases ≤ 5 times ULN.
• No ascites, normal coagulation function, albumin ≥ 35 g/L.
• Liver function: Child-Push score: Class A
• Serum creatinine \< ULN, or calculated creatinine clearance \> 50 ml/min (using the Cockcroft-Gault formula).
• ECOG score 0-1.
• Life expectancy \> 3 months.
• Sign written informed consent.

You may not qualify if:

• Presence of any extrahepatic metastasis and/or primary tumor that cannot be resected with radical surgery.
• Serious arterial embolism or ascites.
• Have bleeding tendency or coagulation disorder.
• Have hypertensive risk or hypertensive encephalopathy.
• Serious uncontrolled systemic complications such as infection or diabetes.
• Clinically significant cardiovascular disease such as cerebrovascular accident (within 6 months prior to enrollment), myocardial infarction (within 6 months prior to enrollment), uncontrolled hypertension despite appropriate medical treatment. Unstable angina, congestive heart failure (NYHA class 2-4), cardiac arrhythmia requiring medication.
• History or physical evidence of central nervous system disease (e.g., primary brain tumor, epilepsy uncontrolled by standard of care, any history of brain metastases or stroke).
• History of other malignancies (except basal cell carcinoma of the skin and/or carcinoma in situ of the cervix after radical surgery) within the past 5 years.
• Treatment with any ongoing investigational drug within the last 28 days prior to the study.
• Any residual toxicity from prior chemotherapy (except alopecia), such as peripheral neuropathy ≥ NCI CTC v4.03 Grade 2, will not be considered for oxaliplatin-containing regimen.
• Hypersensitivity to any drug in the study.
• Pregnant and lactating women.
• Women of childbearing age (\< 2 years after menstruation) or men of childbearing potential who are not using or refuse to use effective non-hormonal contraception (intrauterine contraceptive ring, barrier contraceptives combined with spermicidal gel, or surgical sterilization).
• Unable or unwilling to comply with the study protocol.
• Patients with any other diseases, dysfunction caused by metastatic lesions, or suspected disease found by physical examination, indicating possible contraindications to the use of the investigational drug or putting the patients at high risk of treatment-related complications.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (1)

• Wang DS, Ren C, Li SS, Fong WP, Wu XJ, Xiao J, Li BK, Zheng Y, Ding PR, Chen G, Qiu MZ, Wang ZQ, Wang FH, Luo HY, Wang F, Wang XZ, Wang LY, Xie DJ, Chen T, Li LR, Lu ZH, Zhai XH, Liu TS, Yuan Y, Chen JQ, Tan Q, Pan ZZ, Wan DS, Zhang R, Yuan YF, Xu RH, Li YH. Cetuximab plus FOLFOXIRI versus cetuximab plus FOLFOX as conversion regimen in RAS/BRAF wild-type patients with initially unresectable colorectal liver metastases (TRICE trial): A randomized controlled trial. PLoS Med. 2024 May 10;21(5):e1004389. doi: 10.1371/journal.pmed.1004389. eCollection 2024 May.

  PMID: 38728364 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Irinotecan; Cetuximab; Fluorouracil; Oxaliplatin; Leucovorin

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)

Camptothecin; Alkaloids; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Yuhong Li

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 27, 2018
• First Posted: April 10, 2018
• Study Start: April 15, 2018
• Primary Completion: December 30, 2022
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 3, 2025

Record last verified: 2025-07

Locations

CN (1)