Hepatic Arterial Infusion PUMP Chemotherapy Combined With Systemic Therapy Versus Systemic Therapy Alone as Induction Therapy for Initially Unresectable Colorectal Liver Metastases: a Randomised Controlled Trial
The goal of this randomized clinical trial is to investigate induction treatment with Hepatic Arterial Infusion Pump therapy combined with systemic therapy (HAIP-SYST) in chemotherapy-naive patients with unresectable colorectal liver metastases without extrahepatic disease. The main question it aims to answer is if combined HAIP-SYST improves survival compared to induction treatment with systemic therapy alone. Patients in the control arm will receive systemic therapy according to standard of care. Study procedures experimental arm * Surgery for pump placement and resection of the primary tumor * Pre- and postoperative imaging (CT-anghiography, 99mTc-MAA scintigraphy) * Induction treatment with hepatic arterial infusion pump therapy with Floxuridine combined with systemic therapy Study procedures both arms * Evaluation of resectability status by a National Liver Panel with surgeons and radiologists * Questionnaires for Quality of Life
• Age ≥ 18 years.
• Histologically confirmed colorectal adenocarcinoma.
• Unresectable synchronous CRLM according to a National Liver Panel (CT-scan obtained ≤ 4 weeks prior to registration).
• No extrahepatic metastases. Patients with small (≤ 10 mm) extrahepatic lesions that are not clearly suspicious of metastases are eligible.
• No previous systemic therapy for colorectal cancer.
• Positioning of a catheter for HAIP chemotherapy is technically feasible based on imaging. The default site for the catheter insertion is the gastroduodenal artery (GDA). Accessory or aberrant hepatic arteries are no contra-indication for catheter implantation. The GDA should have at least one branch to the liver. Accessory or aberrant hepatic arteries should be ligated to allow for cross perfusion to the entire liver through intrahepatic shunts. Patients with celiac trunk stenosis are not eligible. Patients with both a replaced right and replaced left hepatic artery are not eligible.
• ECOG performance status 0 or 1.
• Life expectancy of at least 12 weeks.
• Known mutation status of RAS and BRAFV600E.
• Primary tumour in situ and resectable without neoadjuvant therapy.
• Patient is eligible for surgery.
• Patient is eligible for doublet chemotherapy.
• Laboratory requirements: i.e. adequate bone marrow, liver and renal function (obtained within 15 days prior to registration).
‣ Hb ≥ 5.5 mmol/L
⁃ absolute neutrophil count (ANC) ≥1.5 x 109/L
⁃ platelets ≥100 x 109/L
⁃ total bilirubin ≤ 1.5 times the upper limit of normal (ULN)
⁃ ASAT/AST ≤ 5 x ULN
⁃ ALAT/ALT ≤ 5 x ULN
⁃ alkaline phosphatase ≤ 5 x ULN
⁃ Serum creatinine ≤ 1.5 x upper limit of normal or a MDRD (eGFR) ≥ 45 ml/min;
⁃ Prothrombin time or INR \< 1.5 x ULN, unless coumarin derivates are used. All patients using coumarin derivates will be treated with LMWH or DOAC instead.
• Before registration, written informed consent must be given and signed according to ICH/GCP, and national/local regulations.