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

Phase 1

Active, not recruiting

• Conditions: Uveal Melanoma; Liver Metastases
• Interventions: Procedure: Isolated hepatic perfusion; Drug: Ipilimumab; Drug: Nivolumab

• Registration Number: NCT04463368
• Lead Sponsor: Vastra Gotaland Region

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-05
• Study First Submitted QC: 2020-07-05
• Study First Posted: 2020-07-09
• Study Start: 2021-03-08
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-25
• Last Update Posted: 2024-01-26
• Primary Completion: 2024-08-04
• Study Completion: 2024-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Isolated hepatic perfusion	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 A	Nivolumab	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	Isolated hepatic perfusion	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.
Arm A	Ipilimumab	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	Ipilimumab	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.
Arm B	Nivolumab	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.

Primary Outcome Measures

Name	Time	Method
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)	1 year	Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)

Secondary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	2 years	Evaluation of progression-free survival (PFS)
Time to response (TTR)	2 years	Evaluation of time to response (TTR)
Objective response rate (ORR)	2 years	Evaluation of objective response rate (ORR)
Clinical benefit rate (CBR)	2 years	Evaluation of clinical benefit rate (CBR)
Hepatic progression-free survival (hPFS)	2 years	Evaluation of hepatic progression-free survival (hPFS)
Overall survival (OS)	2 years	Evaluation of overall survival (OS)
Duration of response (DOR)	2 years	Evaluation of duration of response (DOR)

Trial Locations

Locations (1)

Sahlgrenska University Hospital; 🇸🇪 Gothenburg, Sweden