Clinical trial NCT05948072: Cetuximab+mFOLFOX6 VS. mFOLFOX6 Alone in RAS/BRAF Wild Type Patients With High-Risk Resectable CRLM
Official title: Pre-and Post-operative Cetuximab Plus mFOLFOX6 Versus mFOLFOX6 Alone in RAS/BRAF Wild Type Patients With High-Risk Resectable Colorectal Liver Metastases
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Colorectal Cancer
Liver Metastases
Lead sponsor: Fudan University
Sponsor class: OTHER
First posted: 2023-07-17
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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;

Primary outcomes:
measure: Event-free survival
timeFrame: 3 years
Secondary outcomes:
measure: overall survival
timeFrame: 5 years
measure: postoperative hospital stay
timeFrame: 30 days post operatively
measure: postoperative complication
timeFrame: After surgery during one month
measure: postoperative mortality
timeFrame: After surgery during 90 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Zhongshan hosptial, Fudan University
Study officials:
affiliation: Fudan University
name: Jianmin Xu, MD
role: PRINCIPAL_INVESTIGATOR
References: