FOLFOX-HAIC as Conversion Treatment for Initially Unresectable Colorectal Liver Metastasis

Phase 2

Recruiting

• Conditions: Colorectal Liver Metastasis (CRLM)
• Interventions: Combination Product: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU]); Procedure: hepatic arterial infusion chemotherapy (HAIC); Drug: Bevacizumab; Drug: Cetuximab (Erbitux); Procedure: liver resection

• Registration Number: NCT06988852
• Lead Sponsor: Tongji Hospital

Brief Summary

Try FOLFOX-HAIC combining bevacizumab or cetuximab for initially unresectable colorectal liver metastasis patients to increase the conversion to resection rate to improve long-term survival outcomes

Detailed Description

Colorectal cancer (CRC) was a common malignancy. Approximately 50% CRC patients would develop either synchronous or metachronous liver metastasis, which served as the leading cause of death in CRC, during the course of their diseases. Complete resection of all liver metastases is a major contributor to long-term survival with a median OS of 35 months, while it is just 20-24 months in modern chemotherapy. However,80%-90% colorectal liver metastasis (CRLM) patients present with initially unresectable diseases and the median OS in untreated patients is only 7.5 months. Liver transplantation achieves a 5-year OS rate of 56% compared to the rate of 9% for systemic chemotherapy, organ shortage and high cost limit its popularization. Conversion treatment refers to applying local and/or systemic treatment for IU-CRLM to eliminate technical or biologic unresectable factors to gain potential resectable states and is associated with a 5-year OS rate of 30%-61% in successful patients, which is non-inferior to those who are initially resectable. However, the conversion to resection rates (CTRRs) with negative margin vary from 1.7% to 66% depending on treatment regimens. So, promoting the conversion ability is the only way to improve long-term survival.

The systemic conversion treatment includes systemic chemotherapy and target agents. It shows high adverse event (AE) rates in practice and the CTRRs varies from 1.7% to 49%, which is unsatisfactory. The locoregional conversion treatment, such as hepatic arterial infusion chemotherapy (HAIC), transarterial chemoembolization (TACE), transarterial radioembolization (TARE) and so on, is only suitable for liver-only metastases. For the reason of CRLM deriving predominant blood supply from hepatic artery while liver parenchyma mainly from portal vein, transarterial interventional therapy may not only improve the CTRRs but also reduce AE rates. It's a pity that the CTRRs in TACE or TARE only range from 7% to 10%. HAIC achieves 17.8%-66% CTRRs depending on different drug regimens. Target agents indeed increases the CTTRs in systemic chemotherapy, but bevacizumab doesn't increases it in FUDR-HAIC and brings unexpectedly biliary toxicity. However, in unresectable hepatocellular carcinoma (uHCC), FOLFOX-HAIC combining with Sintilimab® and bevacizumab achieved a CTRR of 48.2% and no biliary toxicity event occurred. Another study, oxaliplatin-HAIC with systemic chemotherapy plus cetuximab achieved an impressive CTTR of 66% but was only suitable for patients without mutational RAS. Maybe a new regimen, oxaliplatin-based complete arterial infusion regimen combining with bevacizumab or cetuximab for IU-CRLM could achieve a milestone outcome, but no literature had reported it.

In this study, we establish a prospective and consecutive IU-CRLM patient cohort treated with FOLFOX-HAIC combining with bevacizumab or cetuximab to evaluate the CTRR, tumor response, safety and long-term oncological outcomes.

Study Timeline

• Study Start: 2023-05-01
• Status Verified: 2025-05
• Study First Submitted: 2025-05-04
• Study First Submitted QC: 2025-05-23
• Last Update Submitted: 2025-05-23
• Study First Posted: 2025-05-25
• Last Update Posted: 2025-05-25
• Primary Completion: 2030-12-31
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• age 18-75 years
• no history of other malignant diseases
• refuse or progress in prior systemic treatment
• diagnosed as CRLM confirmed by pathology, in spite of whether the primary tumor had been resected
• at least one lesion in the liver could be measured
• left ventricular ejection ≥45%, forced expiratory volume in one second/forced vital capacity≥60% and Eastern Cooperative Oncology Group (ECOG) score of 0-1
• Child-Pugh class A
• adequate organ function, i.e.: white blood cell (WBC) ≥3.0×109/L, neutrophils ≥1.5×109/L, platelet (PLT) ≥75×109/L, total bilirubin ≤30μmol/L, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤200U/L, creatinine ≤150μmol/L

Exclusion Criteria

• extra-hepatic metastasis verified by medical imaging
• unable to tolerate chemotherapy, anesthesia or surgery
• allergy or previous intolerable to any agent of oxaliplatin, leucovorin, 5-Fu, bevacizumab or cetuximab
• tumor spread in abdomen
• cerebral infarction, cerebral hemorrhage, gastrointestinal hemorrhage/perforation within 6 months, coagulation disorders and gastrointestinal ulcer
• primary tumor may not be completely resected
• prior treatment of CRLM with resection, ablation or radiation
• incomplete clinical or follow-up data

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment group	FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])	Patients in the treatment group would undergo FOLFOX-HAIC combining Bevacizumab or Cetuximab
Treatment group	hepatic arterial infusion chemotherapy (HAIC)	Patients in the treatment group would undergo FOLFOX-HAIC combining Bevacizumab or Cetuximab
Treatment group	Bevacizumab	Patients in the treatment group would undergo FOLFOX-HAIC combining Bevacizumab or Cetuximab
Treatment group	Cetuximab (Erbitux)	Patients in the treatment group would undergo FOLFOX-HAIC combining Bevacizumab or Cetuximab
Treatment group	liver resection	Patients in the treatment group would undergo FOLFOX-HAIC combining Bevacizumab or Cetuximab

Primary Outcome Measures

Name	Time	Method
conversion to resection rate	180 days	conversion to resection rate: the number of patients underwent liver resection/total patients underwent FOLFOX-HAIC combining with target agents

Secondary Outcome Measures

Name	Time	Method
drug treatment safety assessment	Baseline up to study termination, assessed up to 12 months.	Any adverse event during treatment that is incompatible with the therapeutic purpose of the medication. The incidence and severity of adverse events and serious adverse events as assessed according to CTCAE v5.0.
objective response rate	From the time of enrollment until disease progression, death, or the end of the study, assessed up to 12 months.	Objective response rate (ORR) was defined as the sum of cases with complete response (CR) and partial response (PR) which assessed by the RECIST 1.1 criteria.

Trial Locations

Locations (1)

Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China