Additional Chemotherapy Administered Directly Into the Liver Using a Chemo Pump in Patients With Bile Duct Cancer Inside the Liver Treatable by Surgery

Official title

Preventing Liver Recurrence After Partial Hepatectomy for Intrahepatic Cholangiocarcinoma Using Adjuvant Hepatic Arterial Infusion Pump Chemotherapy - PUMP IV Trial

Overview

The goal of this clinical trial is to learn if additional chemotherapy by means of a chemo pump can prevent return of disease in adult patients with bile duct cancer in the liver that can be treated with surgery. The main questions it aims to answer are: * Does addition of chemotherapy by means of a chemo pump lead to less return of disease within the liver two years after surgery? * Does addition of chemotherapy by means of a chemo pump lead to longer survival of patients? * Does addition of chemotherapy by means of a chemo pump lead to an increase in quality of life? Participants will receive an implanted chemo pump, through which additional chemotherapy will be given to the liver in addition to surgery.

Interventions

• Combination product Hepatic Arterial Infusion Pump chemotherapy with floxuridin
  Participants in this arm will receive in addition to standard care (surgery) a chemo pump. This pump will provide participants with 4 cycles of treatment with chemotherapy (Floxuridin), each lasting 4 weeks. Total treatment with chemotherapy will last 16 weeks (approx. 4 months)

Primary outcome measures

• Two-year hepatic recurrence free survival (hRFS) [Time frame: From pump implantation until 2 years after that surgery]

Secondary outcome measures (10)

• Overall recurrence free survival (RFS) [Time frame: From pump implantation until the earliest return of disease in the body during the study (up to 5 years after inclusion)]
• Overall survival (OS) [Time frame: From pump implantation until death or lost to follow-up during the study (up to 5 years after inclusion)]
• Post-operative complications [Time frame: From pump implantation until 90 days after surgery]
• Chemotherapy related adverse events (AEs) [Time frame: From inclusion until 4 weeks after the end of treatment with chemotherapy]
• Proportion of patients started with HAIP chemotherapy [Time frame: From pump implantation until the first cycle of HAIP chemotherapy, on average between 4 and 16 weeks after implantation of the HAIP chemopump]
• Quality of life: EORTC QLQ-30 [Time frame: From inclusion until 5 years after surgery]
• Quality of life: EQ-5D [Time frame: From inclusion until 5 years after surgery]
• Cost-effectiveness [Time frame: From implantation of the chemo pump until 2 years after (=timeframe of the primary outcome)]
• Predictive biomarkers in the blood for efficacy of HAIP chemotherapy [Time frame: From implantation of the chemo pump until 1 year after surgery or return of disease (whichever comes first)]
• Predictive biomarkers from liver tissue for efficacy of HAIP chemotherapy [Time frame: From resection until 25 years after (conform applicable laws)]

Eligibility criteria

Inclusion criteria

• 18 years or older
• ECOG or WHO performance status 0 or 1
• Diagnosis of resectable iCCA on imaging. No histological confirmation is needed before surgery, according to standard of care.
• Patient is able to undergo a laparotomy.
• Positioning of a catheter for HAIP chemotherapy is technically feasible based on a CT-scan with early arterial phase with 1mm cuts. The default site for the catheter insertion is the GDA. Accessory or aberrant hepatic arteries are no contraindication for catheter placement.
• Adequate bone marrow, liver, and renal function before inclusion (values may be max. 30 days old)
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^ 9/L
• White blood cell count (WBC) ≥ 2.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Glomerular filtration rate (GFR) ≥ 30 ml/min
• Haemoglobin (Hb) ≥ 5.5 mmol/L
• Total bilirubin ≤ 25 µmol/L
• Written informed consent must be given according to ICH/good clinical practice (GCP), and national/local regulations.

Exclusion criteria

• Presence of extrahepatic disease at the time of first presentation. Patients with locoregional lymph node disease or with small (≤ 1 cm) extrahepatic lesions that are too small to characterize or biopsy are eligible.
• Second primary malignancy, except for adequately treated non-melanoma skin cancer, or other malignancy treated at least 3 years previously without evidence of recurrence or with a life expectancy longer than 5 years.
• Known homozygous dihydropyrimidine dehydrogenase (DPYD) deficiency
• Prior hepatic radiation, ablation, or resection for iCCA.
• Clinical evidence of portal hypertension (ascites, gastroesophageal varices, or portal vein thrombosis). Some postoperative ascites is allowed.
• (Partial) portal vein thrombosis in future liver remnant.
• Pregnant or lactating women.
• History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance for HAIP chemotherapy.
• Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator.
• Organ allografts requiring immunosuppressive therapy.
• Serious infections (uncontrolled or requiring treatment).
• Participation in another interventional study for iCCA with survival as outcome.
• Participation in another prospective study with an interventional medical product.
• Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Netherlands · 1 center

• Erasmus Medical Center — Rotterdam

Identifiers

NCT: NCT06888063 · MEC-2024-0324 · 2024-513726-33-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗