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

NCT04687631 | Recruiting Phase 3

• 1 other identifier: TRUST
• Study Type: interventional
• Target: 508
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer; Liver Metastases

Keywords

Cetuximab; Bevacizumab; Triplet Chemotherapeutic Regimen; Colorectal Cancer; Liver Metastases

Outcome Measures

Primary Outcomes (1)

• Conversion resection rate of liver metastases

  Rate of conversion from initially unresectable liver metastases to resectable ones

  up to 6 months

Secondary Outcomes (7)

• Objective Response Rate

  up to 6 months

• Incidence of adverse events

  up to 6 months

• Progression-Free Survival

  up to 3 years

• Overall Survival

  up to 3 years

• Early tumor shrinkage

  at 8 weeks

Study Arms (2)

mFOLFOXIRI plus Cetuximab

EXPERIMENTAL

Drug: mFOLFOXIRI plus Cetuximab

mFOLFOXIRI plus Bevacizumab

EXPERIMENTAL

Drug: mFOLFOXIRI Plus Bevacizumab

Interventions

mFOLFOXIRI plus Cetuximab DRUG

cetuximab 500mg/m2 + oxaliplatin 85 mg/m2 + irinotecan 165 mg/m2 + folinic acid 400 mg/m2 + 5-fluorouracil 2400 mg/m2 46h infusion starting on day 1, every 2 weeks

mFOLFOXIRI plus Cetuximab

mFOLFOXIRI Plus Bevacizumab DRUG

bevacizumab 5mg/kg + oxaliplatin 85 mg/m2 + irinotecan 165 mg/m2 + folinic acid 400 mg/m2 + 5-fluorouracil 2400 mg/m2 46h infusion starting on day 1, every 2 weeks

mFOLFOXIRI plus Bevacizumab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The primary tumor was confirmed by histology as colorectal adenocarcinoma
• Initially unresectable liver metastases suggested by MDT
• RAS/BRAF gene wild-type states
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jianmin Xu, MD, Ph.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianmin Xu, MD, Ph.D.

CONTACT

86-21-64041990; xujmin@aliyun.com

Wentao Tang, MD, Ph.D.

CONTACT

86-21-64041990; tangwt1988@163.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy director of the department of general surgery

Study Record Dates

• First Submitted: December 27, 2020
• First Posted: December 29, 2020
• Study Start: January 14, 2021
• Primary Completion: March 31, 2025
• Study Completion (Estimated): September 30, 2027
• Last Updated: December 18, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)