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

Sponsor

Fudan University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04525326

Collaborator

(none)

584

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer Liver Metastases	Drug: Cetuximab Drug: Bevacizumab Drug: mFOLFOX/FOLFIRI ( Standard Chemotherapy)	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

584 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Oct 1, 2020

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Nov 1, 2022

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: standard chemotherapy plus Cetuximab

Drug: Cetuximab

mFOLFOX+Cetuximab for Ras / BRAF Wild Type Unresectable Right Colon Cancer Patients With Liver Metastasis

Drug: mFOLFOX/FOLFIRI ( Standard Chemotherapy)

Standard Chemotherapy

Experimental: standard chemotherapy plus Bevacizumab

Drug: Bevacizumab

mFOLFOX+Bevacizumab for Ras / BRAF Wild Type Unresectable Right Colon Cancer Patients With Liver Metastasis

Drug: mFOLFOX/FOLFIRI ( Standard Chemotherapy)

Standard Chemotherapy

Outcome Measures

Primary Outcome Measures

Conversion liver resection rate [up to 6 months]
Rate of conversion from initially unresectable liver metastases to resectable ones

Secondary Outcome Measures

objective response rate [up to 6 months]
rate of objective response for therapy(according to RECIST 1.0)
Incidence of adverse events [up to 6 months]
Incidence of adverse events
Progression free survival [up to 3 years]
Progression free survival
overall survival [up to 5 years]
overall survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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