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

• Status: Recruiting
• Trial end date: 2024-12-31
• Target enrollment: 0
• Participant gender: All

Summary

Evidence suggests that the addition of cetuximab or bevacizumab to doublet regimens could improve response rate and resectability rate of liver metastases and survival in colorectal liver metastases (CRLM). Moreover, it is observed that FOLFOXIRI yields higher response and resection rates compared with doublet regimens. However, which is better in conversion therapy of RAS/BRAF wild-type initially unresectable CRLM, FOLFOXIRI plus cetuximab or bevacizumab, remains unknown.

In this study, RAS/BRAF wild-type colorectal cancer patients with initially unresectable liver-only metastases, as prospectively confirmed by a local multidisciplinary team (MDT) according to predefined criteria, will be randomised between modified FOLFOXIRI (mFOLFOXIRI) plus cetuximab and mFOLFOXIRI plus bevacizumab. Patient imaging will be reviewed for resectability by MDT, consisting of at least one radiologist and three liver surgeons every assessment. MDT review will be performed prior to randomization as well as during treatment, as described in the protocol.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fudan University
• Treatments: Bevacizumab; Cetuximab

Criteria

Inclusion Criteria:

1. The primary tumor was confirmed by histology as colorectal adenocarcinoma

2. Initially unresectable liver metastases suggested by MDT

3. RAS/BRAF gene wild-type states

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

5. Life expectancy ≥ 3 months

6. Good hematological function: neutrophil ≥ 1.5x109 / L and platelet count ≥ 100x109 / L; HB ≥ 9g / dl (within one week before randomization)

7. 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);

8. 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. 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