Conversion Therapy of RAS/BRAF Wild-Type Right-sided Colon Cancer Patients With Initially Unresectable Liver Metastases

Study Overview
=================
Brief Summary
-----------------
The prognosis of patients with metastatic right-sided colon cancer is worse than that of patients with metastatic left-sided cancer. Different guidelines have different recommendations on specific conversion therapy for colorectal liver metastases. The United States NCCN guidelines do not recommend standard chemotherapy combined with anti EGFR monoclonal antibody for patients with right colon cancer. The European ESMO guidelines recommend that patients with Ras / BRAF wild-type right-sided colon cancer should first consider three drugs ± bevacizumab, but considering the objective response rate results, standard chemotherapy + anti EGFR monoclonal antibody is still one of the choices. China CSCO guidelines recommend standard chemotherapy ± bevacizumab, and also recommend standard chemotherapy + cetuximab for patients with right-sided colon cancer. Therefore, the targeted therapy for RAS / BRAF wild-type metastatic right colon cancer is still controversial. Therefore, we are ready to carry out the clinical trial of cetuximab and bevacizumab in conversion therapy for RAS / BRAF wild-type metastatic right colon cancer. The conversion resection rate is the primary point, and the objective response rate, perioperative safety and long-term survival are the secondary points.

Official Title
-----------------
A Prospective Study on the Conversion Therapy of Ras / BRAF Wild Type Right-sided Colon Cancer Patients With Initially Unresectable Liver Metastases: Standard Chemotherapy Plus Cetuximab VS. Standard Chemotherapy Plus Bevacizumab

Conditions
-----------------
Colorectal Cancer, Liver Metastases

Intervention / Treatment
-----------------
* Drug: Cetuximab
* Drug: Bevacizumab
* Drug: mFOLFOX/FOLFIRI ( Standard Chemotherapy)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The primary tumor was confirmed by histology as colorectal adenocarcinoma primary right-sided colorectal adenocarcinoma Radiologic evidence suggests that the initial unresectable liver metastases RAS/BRAF gene wild-type states ECOG was 0   1 Life expectancy ≥ 3 months Good hematological function: neutrophil ≥ 1.5x109/l and platelet count ≥ 100x109 / L; HB ≥ 9g / dl (within one week before randomization) Normal liver and kidney function: serum bilirubin ≤ 1.5x normal upper limit (ULN), alkaline phosphatase ≤ 5x ULN, serum transaminase (AST or ALT) ≤ 5x ULN (within one week before randomization); Sign the written informed consent to participate in the experiment Exclusion Criteria: Patients with liver metastases from colorectal cancer who have previously received targeted therapy, chemotherapy, radiotherapy or interventional therapy Known or suspected extrahepatic metastasis Patients with known hypersensitivity to any component of the study treatment Clinical related coronary heart disease or history of myocardial infarction in the last 12 months or left ventricular ejection fraction below normal range Acute or subacute intestinal obstruction Pregnancy (no pregnancy confirmed by serum / urine β - hCG) or breastfeeding. She had other malignant tumors within 5 years, except for those with skin basal cell carcinoma or cervical cancer Known drug / alcohol abuse No legal capacity or limited legal capacity There is peripheral neuropathy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: standard chemotherapy plus Cetuximab<br> | Drug: Cetuximab<br>* mFOLFOX+Cetuximab for Ras / BRAF Wild Type Unresectable Right Colon Cancer Patients With Liver Metastasis<br>Drug: mFOLFOX/FOLFIRI ( Standard Chemotherapy)<br>* Standard Chemotherapy<br>|
| Experimental: standard chemotherapy plus Bevacizumab<br> | Drug: Bevacizumab<br>* mFOLFOX+Bevacizumab for Ras / BRAF Wild Type Unresectable Right Colon Cancer Patients With Liver Metastasis<br>Drug: mFOLFOX/FOLFIRI ( Standard Chemotherapy)<br>* Standard Chemotherapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conversion liver resection rate | Rate of conversion from initially unresectable liver metastases to resectable ones | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective response rate | rate of objective response for therapy(according to RECIST 1.0) | up to 6 months | 
| Incidence of adverse events | Incidence of adverse events | up to 6 months | 
| Progression free survival | Progression free survival | up to 3 years | 
| overall survival | overall survival | up to 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cetuximab, Bevacizumab, Liver Metastases, Colorectal Cancer, right-sided