NCT02913417

Yttrium90, Ipilimumab, & Nivolumab for Uveal Melanoma With Liver Metastases

A Feasibility Study of Sequential Hepatic Internal Radiation and Systemic Ipilimumab and Nivolumab in Patients With Uveal Melanoma Metastatic to Liver.

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Sponsor: David Minor, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Reports to date show limited efficacy of immunotherapy for uveal melanoma. Recent experimental and clinical evidence suggests synergy between radiation therapy and immunotherapy. The investigators will explore this synergy with a feasibility study of 26 patients with uveal melanoma and hepatic metastases who will receive SirSpheres Yttrium-90 selective internal hepatic radiation followed by immunotherapy with the combination of ipilimumab and nivolumab.

Detailed description

Despite rapid improvements in the treatment of cutaneous melanoma, there has been little advance in therapy for uveal melanoma with hepatic metastases, an fatal orphan disease with no established therapy. Studies by Dr. Sato and others have described some activity for selective internal radiation with Yttrium90 microspheres (SIR-Spheres).There is limited activity as single agents for both the immunotherapy drugs ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1). In cutaneous melanoma the combination of ipilimumab and nivolumab is clearly synergistic with improvement in response rates and progression-free survival over single agents; however this has yet to be established for uveal melanoma. Recent experimental and clinical evidence suggests additional synergy between radiation therapy and immunotherapy. This synergy seems most evident when radiation is given through large fraction stereotactic treatments or brachytherapy. The investigators will explore this synergy with a feasibility study of 18 patients who will receive SirSpheres Yttrium-90 selective internal radiation given through the hepatic artery in two treatments followed by immunotherapy with the combination of ipilimumab and nivolumab. The immunotherapy will be given with the dose and schedule that has been established and FDA-approved for cutaneous melanoma. Because of the generally low toxicity of Yttrium-90 selective internal radiation therapy the investigators feel it can be given in full dosage prior to full dosage of immunotherapy.

Conditions

• Uveal Melanoma
• Hepatic Metastases

Interventions

Type	Name	Description
DEVICE	SIR-Spheres® Yttrium 90	Patient treatment will consist of three parts: first, selective internal radiation with SIR-Spheres Yttrium-90 microspheres with dosage per package insert , reduced to give 35cGymax to normal liver; second, concurrent ipilimumab 1mg/kg and nivolumab 1mg/kg every 3 weeks for 4 doses (immunotherapy part 1); then maintenance nivolumab at 480 every 2 weeks (immunotherapy part 2) until progression or 3 years
DRUG	ipilimumab	ipilimumab 1mg/kg every 3 weeks x 4
DRUG	nivolumab	nivolumab 3mg/kg every 3 weeks x 4 then 480mg q 4 weeks

Timeline

• Start date: 2016-10-10
• Primary completion: 2022-01-01
• Completion: 2023-06-01
• First posted: 2016-09-23
• Last updated: 2021-04-19

Locations

3 sites across 1 country: United States