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

NCT ID: NCT01473004

Last Updated: 2025-11-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-10-31
• Study Completion Date: 2024-12-31

Brief Summary

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).

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.

Conditions

Stage IV Uveal Melanoma

Keywords

Sir-spheres; Liver Metastases; Selective internal radiation; Yttrium-90; Uveal; Melanoma; Ocular melanoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Sir-Spheres®

Intervention Type: DEVICE

Sir-Spheres® Yttrium-90 microspheres given intra-hepatic; once for each lobe involved separated by 4 weeks.

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.

Group Type: EXPERIMENTAL

Sir-Spheres®

Intervention Type: DEVICE

Sir-Spheres® Yttrium-90 microspheres given intra-hepatic; once for each lobe involved separated by 4 weeks.

Interventions

Sir-Spheres®

Sir-Spheres® Yttrium-90 microspheres given intra-hepatic; once for each lobe involved separated by 4 weeks.

Intervention Type: DEVICE

Eligibility Criteria

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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Thomas Jefferson University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Takami Sato, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Carin Gonsalves, MD

Role: PRINCIPAL_INVESTIGATOR

Thomas Jefferson University

Locations

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.kimmelcancercenter.org

Sidney Kimmel Cancer Center

http://hospitals.jefferson.edu/

Thomas Jefferson University Hospital

Other Identifiers

JT 2216

Identifier Type: OTHER

Identifier Source: secondary_id

10D.95

Identifier Type: -

Identifier Source: org_study_id