Cetuximab Plus FOLFOXIRI vs Cetuximab Plus FOLFOX For CRCLM

Cetuximab Plus FOLFOXIRI vs Cetuximab Plus FOLFOX in Patients With Initially Unresectable Colorectal Liver Metastasis

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

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer; Liver Metastases
• Intervention / Treatment: Drug: Irinotecan; Drug: Cetuximab; Drug: 5-fluorouracil; Drug: Oxaliplatin; Drug: Leucovorin

Detailed Description

We intend to carry out a randomized controlled clinical study of cetuximab plus FOLFOXIRI regimen versus cetuximab plus FOLFOX regimen in the first-line treatment of patients with initially unresectable CRLM, to answer the question of whether cetuximab plus FOLFOXIRI regimen can improve the overall ORR, surgical resection rate and OS compared with cetuximab plus FOLFOX regimen in patients with previously untreated, initially unresectable CRLM patients.

• Study Type: Interventional
• Enrollment (Actual): 146
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. Age ≥ 18 years and ≤ 70 years.
2. Histologically confirmed colorectal adenocarcinoma.
3. Liver metastasis confirmed by imaging or pathology.
4. 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.
5. Patients with wild-type RAS.
6. No prior treatment for liver metastases, including chemotherapy, surgery, radiotherapy, transcatheter arterial chemoembolization (TACE), and targeted therapy.
7. 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).
8. Normal hematologic function (platelets > 90 × 109/L; leukocytes > 3 × 109/L; neutrophils > 1.5 × 109/L).
9. Serum bilirubin ≤ 1.5 times the upper limit of normal (ULN) and transaminases ≤ 5 times ULN.
10. No ascites, normal coagulation function, albumin ≥ 35 g/L.
11. Liver function: Child-Push score: Class A
12. Serum creatinine < ULN, or calculated creatinine clearance > 50 ml/min (using the Cockcroft-Gault formula).
13. ECOG score 0-1.
14. Life expectancy > 3 months.
15. Sign written informed consent.
16. Willing and able to be followed up until death or end of study or study termination.

Exclusion criteria:

1. Presence of any extrahepatic metastasis and/or primary tumor that cannot be resected with radical surgery.
2. Serious arterial embolism or ascites.
3. Have bleeding tendency or coagulation disorder.
4. Have hypertensive risk or hypertensive encephalopathy.
5. Serious uncontrolled systemic complications such as infection or diabetes.
6. 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.
7. 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).
8. 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.
9. Treatment with any ongoing investigational drug within the last 28 days prior to the study.
10. 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.
11. Hypersensitivity to any drug in the study.
12. Pregnant and lactating women.
13. 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).
14. Unable or unwilling to comply with the study protocol.
15. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cetuximab Plus FOLFOXIRI; 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; Irinotecan 130 mg/m²; Other Names: CPT-11; Drug: Cetuximab; Cetuximab, iv, 500mg/m2; Other Names: Erbitux; Drug: 5-fluorouracil; 5-FU 2400 mg/m² cont. inf.; Other Names: 5-FU; Drug: Oxaliplatin; oxaliplatin 85 mg/m²; Other Names: L-OHP; Drug: Leucovorin; leucovorin 200 mg/m²; Other Names: FOLINIC ACID
Active Comparator: Cetuximab Plus FOLFOX; 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; Cetuximab, iv, 500mg/m2; Other Names: Erbitux; Drug: 5-fluorouracil; 5-FU 2400 mg/m² cont. inf.; Other Names: 5-FU; Drug: Oxaliplatin; oxaliplatin 85 mg/m²; Other Names: L-OHP; Drug: Leucovorin; leucovorin 200 mg/m²; Other Names: FOLINIC ACID

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Depth of Response	The investigator assesses DpR by measuring the ratio of maximum tumor regression to baseline tumor, and calculates the median value	Each follow up visit, assessed up to 12 months
R0 Resection Rate	Defined as the proportion of patients who achieve complete resection after treatment with cetuximab plus FOLFOXIRI regimen or cetuximab plus FOLFOX regimen according to the study protocol	Each follow up visit, assessed up to 12 months
Early Tumor Shrinkage	Target lesion reduction of a least 20% from the nadir following 4 treatment courses assessed using the RECIST version 1.1 criteria	Each follow up visit, assessed up to 12 months
Progression-Free Survival	Assessed by the investigator using RECIST v1.1, defined as the time from the start of study treatment to disease progression, or relapse after resection of liver metastases, or death due to any cause.	Each follow up visit, assessed up to 60 months
Overall Survival	Defined as the time from the start of study treatment to death due to any cause	Each follow up visit, assessed up to 60 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Investigators: Principal Investigator: Yuhong Li, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2018
• Primary Completion (Actual): December 30, 2022
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: March 27, 2018
• First Submitted That Met QC Criteria: April 9, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 6, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Irinotecan; Cetuximab
• Other Study ID Numbers: ERBIRINOX-CRCLM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No