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

Tongji Hospital

Status and phase

Enrolling

Phase 2

Conditions

Colorectal Liver Metastasis (CRLM)

Treatments

Drug: Bevacizumab

Procedure: liver resection

Combination Product: FOLFOX (oxaliplatin, leucovorin, 5-fluorouracil [5FU])

Drug: Cetuximab (Erbitux)

Procedure: hepatic arterial infusion chemotherapy (HAIC)

Study type

Interventional

Funder types

Other

Identifiers

NCT06988852

CHALLENGE-A1

Details and patient eligibility

About

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

Full 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.

Enrollment

300 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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