SIR-Spheres® 90Y Microspheres Treatment of Uveal Melanoma Metastasized to Liver

An Open-Label, Single Institution, Phase II Study Using Radioactive Yttrium90 Microsphere (SIR-Sphere®) in Uveal Melanoma Patients With Hepatic Metastasis

The purpose of this study is to determine whether radiation provided locally to the liver tumor vasculature environment will demonstrate a response of tumor decline. This radiation may cause the tumor cells to die.

This is a phase II clinical trial to investigate safety and efficacy of radioactive microsphere (SIR-Spheres® microspheres). Uveal melanoma patients with progressing hepatic metastases who received no more than one intra-hepatic arterial treatment will be enrolled. Patients will be first stratified into two groups: Group A, no prior intra-hepatic arterial treatment; Group B, one prior intra-hepatic arterial treatment).

Study Overview

• Status: Completed
• Conditions: Stage IV Uveal Melanoma
• Intervention / Treatment: Device: Sir-Spheres®

Detailed Description

This is an open-label, uncontrolled single institution phase II study for metastatic uveal melanoma. Uveal melanoma patients who received one or less prior trans-arterial embolization treatment of hepatic metastasis are eligible. Patients will be stratified into two groups: Group A, no prior intra-hepatic arterial treatment, n=24; Group B, one prior hepatic trans-arterial embolization treatment, n=24. They will be treated with intra-hepatic arterial infusion of Yttrium-90 radioactive microspheres (SIR-Spheres® microspheres).

Within 4 weeks prior to radiosphere treatment, patients undergo the pre-assessment angiogram and technetium-99m-labelled macroaggregated albumin (99m Tc -MAA) nuclear scan to block the collateral flow to non-target organs and to calculate the shunting rate to the lung. Once patients meet the eligibility criteria of the study, the radiosphere treatment will be given. The Yttrium-90 radioactive microsphere treatment generally consists of two sequential uni-lobar treatments, approximately 4 weeks (3 to 5 weeks) apart. In selected patients, if clinically feasible, a biopsy of hepatic metastasis will be obtained prior to radiosphere treatment to investigate the correlation between efficacy of treatments and molecular characteristics of metastatic uveal melanoma.

The side effects of Yttrium-90 radioactive microspheres will be monitored every 2 weeks for one month following each treatment and then every month for three months after the last radiosphere treatment. The efficacy of radiosphere treatment will be evaluated every 3 months from the last treatment for 2 years until disease progression or death.

If patients experience grade 3 toxicity after the first treatment with Yttrium-90 radioactive microspheres, the second radiosphere treatment will be held until the resolution of toxicity to grade 1 or less or for a maximum of 6 weeks. The dose of the second radiosphere treatment will be decreased by 50% for liver-related grade 3 toxicity. A dose reduction will not be considered for grade 3 GI toxicity unless the next treatment is repeated to the same hepatic lobe. The study treatment will be discontinued for grade 4 toxicity or if patients do not recover from the grade 3 toxicity to at least a grade 1 within 6 weeks.

The study will require two years of accrual with an additional two years of follow-up for survival analysis.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• must have diagnosis of metastatic melanoma liver disease by histological confirmation
• one measurable untreated or progressed liver lesion
• less than 50% liver involvement
• must have ECOG performance status of 0-1
• must have adequate renal and bone marrow function as: serum creatinine ≤ 2.0 mg/dl, granulocyte count ≥1000/mm3 and platelet count ≥100,000/mm3
• must have adequate liver function as: total bilirubin <1.6 mg/ml and albumin >3.0 g/dl

Exclusion Criteria:

• failure to meet any of the inclusion criteria
• solitary liver metastasis that is amenable to surgical removal
• previous treatment with isolated hepatic perfusion
• systemic chemotherapy within 2 weeks of study entry
• significant shunting to the lung (>20%) as identified on Technetium-99m-macro-aggregated albumin nuclear medicine break-through scan
• unsuccessful closure of collateral blood flows from the hepatic artery to non-targeted organs such as the GI tract
• symptomatic liver failure including ascites and hepatic encephalopathy
• metastasis outside of liver requiring systemic treatment within 3 months
• untreated brain metastasis
• main portal vein occlusion or inadequate collateral flow
• uncontrolled hypertension or congestive heart failure
• acute myocardial infarction within 6 months
• medical complications with implication of less than 6 month survival
• uncontrolled severe bleeding tendency or active GI bleed
• significant allergic reaction to iodinated contrast
• previous radiation that includes the liver in the main radiation field
• pregnant or breast-feeding women
• biliary obstruction, stent, or prior biliary surgery including sphincterotomy but excluding cholecystectomy
• children under the age of 18

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: no prior intra-hepatic arterial treatment; Patients with no prior intra-hepatic arterial treatment will be treated with intra-hepatic arterial infusion of Yttrium-90 radioactive microspheres (SIR-Spheres® microspheres). Sir-Spheres® Yttrium-90 microspheres given intra-hepatic; once for each lobe involved separated by 4 weeks.	Device: Sir-Spheres®; Sir-Spheres® Yttrium-90 microspheres given intra-hepatic; once for each lobe involved separated by 4 weeks.
Experimental: Group B: one prior hepatic trans-arterial embolization treatment; Patients with one prior hepatic trans-arterial embolization treatment will be treated with intra-hepatic arterial infusion of Yttrium-90 radioactive microspheres (SIR-Spheres® microspheres). Sir-Spheres® Yttrium-90 microspheres given intra-hepatic; once for each lobe involved separated by 4 weeks.	Device: Sir-Spheres®; Sir-Spheres® Yttrium-90 microspheres given intra-hepatic; once for each lobe involved separated by 4 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Benefit Rate of Previously Treated and Naive Patients	Evaluation of clinical benefit includes status of complete and partial response as well as stable disease	3 months post final treatment, an average of 4 months
Number of Patients With Adverse Events	Adverse events except for baseline symptoms will be collected from start of first treatment to 3 months post final treatment	3 months post final treatment, an average of 4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival (OS) is measured from the start of the treatment to patient death. Date and cause of death will be recorded. The cause of death will be categorized as either cancer-related or cancer-unrelated.	From date of first SIR-Spheres® administration until the date of death from any cause, assessed up to 6 years
Progression Free Survival	Period of time without progression of liver metastasis	2 years post treatment, an average of 10 months
Duration of Response		2 years post treatment, an average of 10 months

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Investigators: Principal Investigator: Carin Gonsalves, MD, Thomas Jefferson University; Principal Investigator: Takami Sato, MD, Thomas Jefferson University

Publications and helpful links

Helpful Links

• Thomas Jefferson University Hospital
• Sidney Kimmel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2011
• Primary Completion (Actual): July 7, 2022
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: November 14, 2011
• First Submitted That Met QC Criteria: November 14, 2011
• First Posted (Estimated): November 17, 2011

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: October 30, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Melanoma; Liver Metastases; Ocular melanoma; Yttrium-90; Sir-spheres; Selective internal radiation; Uveal
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Eye Diseases; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Eye Neoplasms; Uveal Diseases; Skin and Connective Tissue Diseases; Uveal Neoplasms; Melanoma; Uveal Melanoma
• Other Study ID Numbers: 10D.95; JT 2216 (Other Identifier: JeffTrial Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes