Efficacy of Adjuvant Hepatic Arterial Infusion of Floxuridine Post-Resection in Low-Risk Resectable Colorectal Liver Metastases: A Randomized Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of surgery combined with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy, as measured by progression-free survival (PFS), compared to surgery alone in patients with resectable colorectal liver metastases and a low clinical risk score (CRS 0-2). This is clinically relevant as it aims to determine whether the addition of HAIP chemotherapy can improve outcomes in this patient population, potentially leading to changes in treatment protocols for colorectal liver metastases.

Secondary objectives include:

• Comparing overall survival between the two treatment arms.
• Assessing progression-free survival in the liver between the two arms.
• Evaluating postoperative complications and adverse events between the two arms.
• Comparing quality of life between the two arms.
• Evaluating the cost-effectiveness of HAIP chemotherapy, expressed by the incremental cost-effectiveness ratio.
• Determining whether CT angiography can replace a nuclear medicine scan to rule out extrahepatic perfusion of the pump.
• Identifying predictive biomarkers for the efficacy of HAIP chemotherapy.
• Establishing the systemic pharmacokinetic profile of intra-arterial administration of floxuridine.

The clinical trial involves participants diagnosed with **resectable colorectal liver metastases** without extrahepatic disease. The study population includes both male and female subjects aged 18 years and older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Participants are required to have a Clinical Risk Score (CRS) of 0-2 and must have histologically confirmed colorectal cancer. Additionally, the trial includes individuals with radiologically confirmed colorectal liver metastases that are amenable to resection or open ablation. The trial does not involve a vulnerable population. Participants must have adequate bone marrow, liver, and renal function, as assessed within 15 days prior to inclusion. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the efficacy of adjuvant hepatic arterial infusion pump (HAIP) chemotherapy following the resection of colorectal liver metastases in patients with a low clinical risk score. This study is a **randomized controlled trial** aimed at comparing the progression-free survival (PFS) of patients undergoing surgery with HAIP chemotherapy versus surgery alone. The trial is expected to run until June 2026, with recruitment having commenced in August 2018. Participants will be involved in the study for a maximum treatment period of 24 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (≥18 years), ECOG performance status of 0 or 1, and a Clinical Risk Score (CRS) of 0-2. Additional criteria include histologically confirmed colorectal cancer, radiologically confirmed colorectal liver metastases amenable to resection or open ablation, and adequate bone marrow, liver, and renal function. The screening will also assess the technical feasibility of catheter positioning for HAIP chemotherapy using a CT scan with early arterial phase.

Following the inclusion visit, participants will attend regular follow-up visits to monitor their health status, treatment efficacy, and any adverse events. These visits will also evaluate secondary endpoints such as overall survival, progression-free survival in the liver, postoperative complications, quality of life, and cost-effectiveness. The pharmacokinetic profile of intra-arterial administration of floxuridine and predictive biomarkers for the efficacy of HAIP chemotherapy will also be assessed.

The study will conclude with an end-of-study visit, where final assessments will be conducted to gather comprehensive data on the primary and secondary endpoints. Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with the study protocol, or if the investigator deems it in the participant's best interest. The trial is conducted under strict ethical guidelines to ensure the safety and well-being of all participants.

The clinical trial involves the use of **Floxuridin**, a derivative of 5-fluorouracil (5-FU), which is employed as an antimetabolic drug in oncology. Floxuridin is administered in the form of an intra-arterial infusion, specifically targeting hepatic arterial infusion pump (HAIP) chemotherapy. The pharmaceutical form of Floxuridin is designated as PHF00082MIG. The maximum daily dose of Floxuridin is 0.12 units, with a total maximum dose of 6.72 units over the course of the treatment. The treatment period is set for a maximum of 24 weeks. The administration route is intra-arterial, ensuring direct delivery to the liver, which is critical for patients with resectable colorectal liver metastases.

In this randomized controlled trial, the experimental treatment with Floxuridin is compared against the standard-of-care therapy, which involves surgery alone. The primary objective is to assess the efficacy of surgery combined with adjuvant HAIP chemotherapy, as measured by progression-free survival (PFS), in patients with a low clinical risk score (CRS 0-2). The trial does not involve the use of a placebo or any other comparator treatment. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy in this clinical trial will be assessed by comparing the **progression free survival (PFS)** of patients undergoing surgery combined with adjuvant hepatic arterial infusion pump (HAIP) chemotherapy to those undergoing surgery alone. The primary endpoint is progression free survival, which will be measured to evaluate the effectiveness of the treatment. Secondary endpoints include overall survival, progression free survival in the liver, postoperative complications, adverse events, quality of life, cost effectiveness, the accuracy of CT angiography to detect extrahepatic perfusion, the pharmacokinetic profile of intra-arterial administration of floxuridine, and predictive biomarkers for the efficacy of HAIP chemotherapy.

The trial will involve patients with resectable colorectal liver metastases who have a low clinical risk score (CRS 0-2). The efficacy parameters will be collected and analyzed at various timepoints throughout the study, although specific timepoints are not detailed in the provided data. The study aims to determine the effectiveness of the treatment regimen in improving patient outcomes, with a focus on the primary endpoint of progression free survival.