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

Phase 3

• Conditions: Colorectal Cancer; Liver Metastases
• Interventions: Drug: Cetuximab; Drug: Bevacizumab; Drug: mFOLFOX/FOLFIRI ( Standard Chemotherapy)

• Registration Number: NCT04525326
• Lead Sponsor: Fudan University

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2020-08
• Study First Submitted: 2020-08-21
• Study First Submitted QC: 2020-08-23
• Last Update Submitted: 2020-08-23
• Study First Posted: 2020-08-25
• Last Update Posted: 2020-08-25
• Study Start: 2020-10-01
• Primary Completion: 2022-10-01
• Study Completion: 2022-11-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 584

Inclusion Criteria

1. The primary tumor was confirmed by histology as colorectal adenocarcinoma
2. primary right-sided colorectal adenocarcinoma
3. Radiologic evidence suggests that the initial unresectable liver metastases
4. RAS/BRAF gene wild-type states
5. ECOG was 0 ~ 1
6. Life expectancy ≥ 3 months
7. Good hematological function: neutrophil ≥ 1.5x109/l and platelet count ≥ 100x109 / L; HB ≥ 9g / dl (within one week before randomization)
8. 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);
9. Sign the written informed consent to participate in the experiment

Exclusion Criteria

1. Patients with liver metastases from colorectal cancer who have previously received targeted therapy, chemotherapy, radiotherapy or interventional therapy
2. Known or suspected extrahepatic metastasis
3. Patients with known hypersensitivity to any component of the study treatment
4. Clinical related coronary heart disease or history of myocardial infarction in the last 12 months or left ventricular ejection fraction below normal range
5. Acute or subacute intestinal obstruction
6. Pregnancy (no pregnancy confirmed by serum / urine β - hCG) or breastfeeding.
7. She had other malignant tumors within 5 years, except for those with skin basal cell carcinoma or cervical cancer
8. Known drug / alcohol abuse
9. No legal capacity or limited legal capacity
10. There is peripheral neuropathy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
standard chemotherapy plus Cetuximab	Cetuximab	-
standard chemotherapy plus Cetuximab	mFOLFOX/FOLFIRI ( Standard Chemotherapy)	-
standard chemotherapy plus Bevacizumab	mFOLFOX/FOLFIRI ( Standard Chemotherapy)	-
standard chemotherapy plus Bevacizumab	Bevacizumab	-

Primary Outcome Measures

Name	Time	Method
Conversion liver resection rate	up to 6 months	Rate of conversion from initially unresectable liver metastases to resectable ones

Secondary Outcome Measures

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