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

Phase 3

Not yet recruiting

• Conditions: Liver Metastases; Colorectal Cancer
• Interventions: Drug: mFOLFOX 6; Drug: mFOLFOX6 + Cetuximab

• Registration Number: NCT05948072
• Lead Sponsor: Fudan University

Brief Summary

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.

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 Timeline

• Status Verified: 2023-07
• Study First Submitted: 2023-07-09
• Study First Submitted QC: 2023-07-14
• Last Update Submitted: 2023-07-14
• Study Start: 2023-07-15
• Study First Posted: 2023-07-17
• Last Update Posted: 2023-07-17
• Primary Completion: 2026-07-15
• Study Completion: 2026-07-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 250

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
mFOLFOX6	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.
mFOLFOX6 + Cetuximab	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.

Primary Outcome Measures

Name	Time	Method
Event-free survival	3 years	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

Secondary Outcome Measures

Name	Time	Method
postoperative complication	After surgery during one month	Patients will be evaluated for surgical morbidity during 1 month. Postoperative morbidity will be scored according 'Clavien-Dindo Grade'.
overall survival	5 years	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.
postoperative hospital stay	30 days post operatively	The postoperative hospital stay is defined as the number of date from the first day after operation to discharge.
postoperative mortality	After surgery during 90 days	any death occured within 90 days after the last resection of primary and metastatic lesions

Trial Locations

Locations (1)

Zhongshan hosptial, Fudan University; 🇨🇳 Shanghai, China