Cetuximab+mFOLFOX6 VS. mFOLFOX6 Alone in RAS/BRAF Wild Type Patients With High-Risk Resectable CRLM

Pre-and Post-operative Cetuximab Plus mFOLFOX6 Versus mFOLFOX6 Alone in RAS/BRAF Wild Type Patients With High-Risk Resectable Colorectal Liver Metastases

For patients with initially resectable colorectal cancer liver metastases who have high-risk factors, neoadjuvant therapy is currently considered a consensus approach. However, there is ongoing debate regarding the optimal treatment strategy. Our study aims to investigate whether the addition of cetuximab to neoadjuvant chemotherapy improves outcomes compared to neoadjuvant chemotherapy alone. The objective of this phase III clinical trial is to determine whether the combination of cetuximab and mFOLFOX6 chemotherapy is superior to neoadjuvant mFOLFOX6 chemotherapy alone for patients with initially resectable colorectal cancer liver metastases who have wild-type RAS/BRAF and high-risk factors.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer; Liver Metastases
• Intervention / Treatment: Drug: mFOLFOX6 + Cetuximab; Drug: mFOLFOX 6

Detailed Description

Primary

• To determine whether the addition of cetuximab to neoadjuvant mFOLFOX6 chemotherapy results in improved event-free survival when compared with neoadjuvant mFOLFOX6 chemotherapy alone in patients with high-risk & RAS/BRAF-wild-type & resectable colorectal liver metastases.

Secondary

• To evaluate the overall survival of patients treated with these regimens.
• To evaluate the quality of life of patients treated with these regimens.
• To evaluate the preoperative remission rate, safety, surgical complications, actual resection rate, pathological resection status of patients treated with these regimens.

• Study Type: Interventional
• Enrollment (Estimated): 250
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jianmin Xu, MD; Phone Number: 86-021-64041990; Email: xujmin@aliyun.com
• Study Contact Backup: Name: Dexiang Zhu, MD; Phone Number: 86-13636443958; Email: 13636443958@163.com

Study Locations

• China
  • Shanghai, China, 200032
    • Zhongshan Hosptial, Fudan University
    • Contact: Jianmin Xu, PhD; Phone Number: +86-13501984869; Email: xujmin@aiiyun.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histological proof of colorectal adenocarcinoma;
2. Age ≥ 18 years and ≤75 years;
3. RAS wild type；
4. CRS≥3；
5. Simultaneous liver-limited metastases;
6. At least one measurable liver metastases;
7. World Health Organization (WHO) performance status 0-1;
8. Life expectancy ≥ 3 months;
9. Adequate hematologic function: absolute neutrophil count (ANC)≥1.5×109/l, platelets≥100×109/l, and hemoglobin(HB) ≥ 9g/dl;
10. Adequate liver and renal function: total bilirubin ≤2.0 mg/dl, serum transaminases ≤ 5x upper limit of normal(ULN), and serum creatinine ≤ 1.5x ULN and creatinine clearance ≥ 30 ml/min;
11. Written informed consent.

Exclusion Criteria:

1. Previous systemic treatment for metastatic disease;
2. Previous surgery for metastatic disease;
3. Extrahepatic metastases;
4. Unresectable primary tumor;
5. Major cardiovascular events (myocardial infarction, severe/unstable angina, congestive heart failure, CVA) within 12 months before randomisation;
6. Acute or subacute intestinal obstruction;
7. Second primary malignancy within the past 5 years;
8. Drug or alcohol abuse;
9. No legal capacity or limited legal capacity;
10. Pregnant or lactating women;
11. Uncontrolled hypertension, or unsatisfactory blood pressure control with ≥3 antihypertensive drugs;
12. Peripheral neuropathy;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: mFOLFOX6 + Cetuximab; Cetuximab + mFOLFOX6: Cetuximab (500mg/m2 IV ) will be given. Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: mFOLFOX6 + Cetuximab; Cetuximab + mFOLFOX6: Cetuximab (500mg/m2 IV ) will be given. Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Active Comparator: mFOLFOX6; mFOLFOX6: Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.	Drug: mFOLFOX 6; mFOLFOX6: Oxaliplatin (85 mg/m2 IV over 2 h on day 1), Leucovorin calcium (350 mg/m2 IV over 2 h on day 1) plus a bolus of 5FU (400 mg/m2) followed by a 46h-48h IV infusion of 5FU 2400 mg/m2 will be repeated for every 2 weeks. The regimens repeat every 2 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival	The Event-free survival (EFS) was defined as the period from the start of initial medication to the date of tumor relapse, progression, or death	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
postoperative hospital stay	The postoperative hospital stay is defined as the number of date from the first day after operation to discharge.	30 days post operatively
postoperative complication	Patients will be evaluated for surgical morbidity during 1 month. Postoperative morbidity will be scored according 'Clavien-Dindo Grade'.	After surgery during one month
postoperative mortality	any death occured within 90 days after the last resection of primary and metastatic lesions	After surgery during 90 days
overall survival	The overall survival (OS) was defined as the period from the start of initial medication until death from any cause, at which point the data was censored.	5 years

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Jianmin Xu, MD, Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2023
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 15, 2026

Study Registration Dates

• First Submitted: July 9, 2023
• First Submitted That Met QC Criteria: July 14, 2023
• First Posted (Actual): July 17, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 14, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm Metastasis; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: NEO-HR-CRLM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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