Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Eye Diseases

Rare Diseases

Neoplasm Metastasis

Melanoma

Uveal Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neoplastic Processes

Eye Neoplasms

Uveal Diseases

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Central Nervous System Depressants

All Drugs and Chemicals

Antineoplastic Agents

Hematinics

Anesthetics

Melphalan

Nivolumab

Ipilimumab

Liver Extracts

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients will be treated with IHP followed by 4 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.

Patients will be treated with 1 course of ipilimumab 3mg/kg and nivolumab 1mg/kg followed by IHP after 3 weeks and then another 3 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.

The procedure is performed under general anaesthesia. The caval vein is isolated infrahepatically above the renal veins and suprahepatically between the diaphragm and the pericardium. A catheter is placed in the retrohepatic portion of the caval vein for perfusion outflow. The portal vein is clamped and the proper hepatic artery is cannulated via the gastroduodenal artery. The liver perfusion is performed at a rate of 8- 9 ml/kg/min with a target liver temperature of 40 degrees Celsius. The leakage from the system was continuously recorded using Technetium labelled albumin (Vasculosis) injected into the perfusion circuit. Melphalan (1 mg/kg bodyweight divided into two doses, given 30 minutes apart) is added to the perfusion system. The perfusion is then continued for 60 minutes, after which the perfusion was discontinued.

Isolated hepatic perfusion

4 courses of ipilimumab 3mg/kg every third week

4 courses of nivolumab 1mg/kg every third week

Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumour, metastatic disease will develop in approximately 35%-50% of the patients within 10 years. The liver is the most common site for metastases, and about 50% of the patients will have isolated liver metastases. Isolated hepatic perfusion is a regional treatment where the liver is completely isolated from the systemic circulation, allowing a high concentration of chemotherapy to be perfused through the liver with minimal systemic exposure. The introduction of modern immunotherapy in the treatment arsenal for cutaneous melanoma also creates hope for patients with uveal melanoma metastases. However, the results of immunotherapy have so far been disappointing. The reason for the low efficacy could be that uveal melanoma develops in the immune privileged eye.

The hypothesis in this trial is that isolated hepatic perfusion with melphalan causes an immunogenic type of cell death by local tumour destruction while leaving the immune-system intact. This will cause an activation of the immune-system and the addition of ipilimumab and nivolumab will enhance this effect, ultimately increasing the treatment efficacy.

The primary objective of this trial is to evaluate the safety and tolerability of isolated hepatic perfusion together with ipilimumab and nivolumab when given at the same time or as a sequenced regimen. The study design is a phase I randomized controlled, multicentre, open-label trial. Active follow-up will be performed for 2 years. Patients will be randomized after diagnoses of metastatic disease to one of the following treatment arms:

Arm A. Patients will be treated with IHP followed by 4 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.

Arm B. Patients will be treated with 1 course of ipilimumab 3mg/kg and nivolumab 1mg/kg followed by IHP after 3 weeks and then another 3 courses of ipilimumab 3mg/kg and nivolumab 1mg/kg every third week followed by continued nivolumab 480mg q4w up to 1 year.

Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases

SCANDIUM II Trial - A Phase I Randomized Controlled Multicentre Trial of Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases

Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

Evaluation of objective response rate (ORR)

Evaluation of clinical benefit rate (CBR)

Evaluation of progression-free survival (PFS)

Evaluation of hepatic progression-free survival (hPFS)

Bristol-Myers Squibb

Vastra Gotaland Region

Principal Investigator

Digestive System Diseases

Liver Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Herbal and Botanical

Kava

Device: Liver-PILP kit The Liver-PILP kit (three devices) is composed of percutaneous, disposable (single-use), catheter-based devices for targeted, isolated, organ specific (liver), drug delivery and perfusion with high dose drugs.

1. The Portal Vein Device (PVD): balloon catheter to occlude the portal vein and allow aspiration through a central lumen for portal veno-venous bypass.
2. The Hepatic Artery Device (HAD): balloon catheter to occlude arterial flow to the liver.
3. The Vena Cava Device (VCD): catheter based device to isolate and access hepatic outflow to vena cava by creating a closed chamber in vena cava at ostia of the hepatic veins while maintaining central vena cava blood flow from lower extremities to right atrium through reduced central lumen.

Liver-PILP kit

Eric Van Cutsem, Prof MD PhD

Marc Van den Eynce, MD

Pierre Goffette, Prof MD

Marie-Agnes Docquier, MD

Michel Van Boven, Prof MD

Amine Matta, Prof MD

Audrey Pospiech, MD

Renaud Lhommel, MD

Luc Defreyne, Prof MD PhD

Karen Geboes, Prof MD PhD

Elilsabeth Dhondt, MD

Patrick Wouters, Prof MD Phd

Filip De Somer, Prof RN Phd

Sylvie Rottey, Prof MD PhD

Chris Verslype, Prof MD Phd

Geert Maleux, Prof MD PhD

Marc Van de Velde, Prof MD PhD

Diethard Monbaliu, Prof MD PhD

Karen Geboes, Prof MD Phd

Marc Van den Eynde, MD

The purpose of this study is to determine whether the PILP-kit can be safely used, within specific performance parameters, to isolate and perfuse the liver with a chemotherapeutic drug for the treatment of patients with unresectable liver metastases.

The objective of this Medical Device Study, is to demonstrate the feasibility of the liver PILP intervention.

The liver PILP intervention will be considered feasible if the procedure is demonstrated to be safe and the liver PILP kit performs according to specifications.

Liver-PILP First-in-Man

First In-vivo Trial of the Liver Percutaneous Isolated Localized Perfusion (PILP) Set for the Treatment of Liver Metastases

The liver PILP intervention will be considered feasible if the intervention is demonstrated to be safe and the PILP kit performs according to specifications related to localization, flow rates and retrieval of devices.

Celerion

Cromsource

Medical Device Works NV SA

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases	NCT04463368	Uveal Melanoma Liver Metastase...	Isolated hepati... Ipilimumab Nivolumab	18 Years -	Vastra Gotaland Region
Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases	NCT04463368	Uveal Melanoma Liver Metastase...	Isolated hepati... Ipilimumab Nivolumab	18 Years -	Vastra Gotaland Region
Isolated Hepatic Perfusion in Combination With Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastases	NCT04463368	Uveal Melanoma Liver Metastase...	Isolated hepati... Ipilimumab Nivolumab	18 Years -	Vastra Gotaland Region
Liver-PILP First-in-Man	NCT01250158	Liver Metastase...	Liver-PILP kit	18 Years -	Medical Device Works NV SA
Liver-PILP First-in-Man	NCT01250158	Liver Metastase...	Liver-PILP kit	18 Years -	Medical Device Works NV SA

Spots Global Cancer Trial Database for isolated hepatic perfusion