Journal Article

Combining Hepatic Percutaneous Perfusion with Ipilimumab plus Nivolumab in advanced uveal melanoma (CHOPIN): study protocol for a phase Ib/randomized phase II trial

Kapiteijn, E., Lutjeboer, J., Tong, T. M. L., van der Meer, R. W., Zoethout, R. W. M., Blank, C. U., van der Kooij, M. K., Martini, C. H., Tijl, F. G. J., Burgmans, M. C., van Persijn van Meerten, E. L., Speetjens, F. M., van Erkel, A. R.

2022

Overview

Background While immune checkpoint inhibition (ICI) has revolutionized the treatment of metastatic cutaneous melanoma, no standard treatments are available for patients with metastatic uveal melanoma (UM). Several locoregional therapies are effective in the treatment of liver metastases, such as percutaneous hepatic perfusion with melphalan (M-PHP). The available literature suggests that treatment with ICI following locoregional treatment of liver UM metastases can result in clinical response. We hypothesize that combining M-PHP with ICI will lead to enhanced antigen presentation and increased immunomodulatory effect, improving control of both hepatic and extrahepatic disease. Methods Open-label, single-center, phase Ib/randomized phase II trial, evaluating the safety and efficacy of the combination of M-PHP with ipilimumab (anti-CTLA-4 antibody) and nivolumab (anti-PD-1 antibody) in patients with unresectable hepatic metastases of UM in first-line treatment, with or without the limited extrahepatic disease. The primary objective is to determine the safety, toxicity, and efficacy of the combination regimen, defined by maximum tolerated dose (MTD) and progression-free survival (PFS) at 1 year. Secondary objectives include overall survival (OS) and overall response rate (ORR). A maximum of 88 patients will be treated in phase I and phase II combined. Baseline characteristics will be described with descriptive statistics ( t -test, chi-square test). To study the association between risk factors and toxicity, a logistic regression model will be applied. PFS and OS will be summarized using Kaplan-Meier curves. Discussion This is the first trial to evaluate this treatment combination by establishing the maximum tolerated dose and evaluating the efficacy of the combination treatment. M-PHP has shown to be a safe and effective treatment for UM patients with liver metastases and became the standard treatment option in our center. The combination of ICI with M-PHP is investigated in the currently described trial which might lead to a better treatment response both in and outside the liver. Trial Registration This trial was registered in the US National Library of Medicine with identifier NCT04283890 . Registered as per February 2020 - Retrospectively registered. EudraCT registration number: 2018-004248-49. Local MREC registration number: NL60508.058.19.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Advanced uveal melanoma / Biomedicine / Care and treatment / Chemotherapy, Cancer, Regional Perfusion - adverse effects / Clinical medicine / Clinical Trials, Phase I as Topic / Clinical Trials, Phase II as Topic / Complications and side effects / Consent / Evaluation / Health Sciences / Human subjects / Humans / Immunotherapy / Ipilimumab / Ipilimumab - adverse effects / Liver / Liver metastases / Medical prognosis / Medical research / Medicine / Medicine & Public Health / Melanoma / Melanoma - drug therapy / Metastasis / Monoclonal antibodies / Nivolumab - adverse effects / Oncology / Patient outcomes / Patients / Percutaneous hepatic perfusion / Perfusion (Physiology) / Randomized Controlled Trials as Topic / Registration / Statistics for Life Sciences / Study Protocol / Targeted cancer therapy / Tumors / Uveal Neoplasms - drug therapy