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

Fudan University

Status and phase: Not yet enrolling; Phase 3

Conditions: Liver Metastases; Colorectal Cancer

Treatments: Drug: mFOLFOX 6; Drug: mFOLFOX6 + Cetuximab

Study type: Interventional

Funder types: Other

Identifiers

NCT05948072

NEO-HR-CRLM

Details and patient eligibility

About

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.

Full 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.

Enrollment: 250 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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;

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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250 participants in 2 patient groups

mFOLFOX6 + Cetuximab

Experimental group

Description:

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.

Treatment:

Drug: mFOLFOX6 + Cetuximab

mFOLFOX6

Active Comparator group

Description:

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.

Treatment:

Drug: mFOLFOX 6