Radioembolization of Primary and Secondary Liver Malignancies and The Effect On The Immune System

Not Applicable

Recruiting

• Conditions: Hepatocellular Carcinoma; Secondary Malignant Neoplasm of Liver
• Interventions: Other: Yttrium-90

• Registration Number: NCT03889093
• Lead Sponsor: University of Minnesota

Brief Summary

The goal of this study is to understand the immunologic effects radioembolization has on the immune system. This will be done by evaluating the changes on biopsy, peripheral blood monocytes, and cytokines.

Detailed Description

This is a single institution non-interventional study designed to evaluate the immune reaction to radioembolization (RE) of primary and secondary malignancies of the liver.

RE has been established as a standard of care treatment for both primary and secondary cancers of the liver. The treatment consists of a mapping, or planning angiogram, followed by a delivery angiogram where the dose of yttrium 90 (y90) is delivered. Data has been published on the immune modification powers of external beam radiation (XRT). However, very little data is available on the ways in which RE modifies the immune system. The goal of this study is to determine changes in the peripheral blood monocytes, cytokines and the treated and untreated liver tumors through sample collection prior to and for 12 weeks after standard of care RE.

The prior to, the RE delivery procedure patients will have a blood draw to evaluate for levels of 11 immunologically relevant cytokines (IL-1α, IL-1β, IL-2, IL-6, IL-10, IL-12p70, IL-18, TNFα, IFN-ϒ, Fit ligand 3, and MCP-1). These blood draws will be repeated at 7 days (- 2 days, + 5 days), 4 weeks (± 2 weeks) and 12 weeks (± 2 weeks) after RE.

The patients will also have the infiltration of immune relative cells into treated tumors evaluated. This will be done by the patients undergoing biopsy of the largest tumor to be treated prior to treatment and at 2 weeks (±7 days) following RE. If patients have other areas of tumor, which are not included in the initial treatment site, these areas will also be biopsied.

Finally, the change in immunologically important peripheral lymphocytes will be collected. This will be done with a blood draw on the day of, but prior to RE serving as an internal control. Patients will then also have blood draws performed at 7 days (±2 days), 4 weeks (± 2 weeks) and 12 weeks (± 2 weeks) after RE.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2018-08-09
• Study First Submitted: 2019-03-12
• Study First Submitted QC: 2019-03-21
• Study First Posted: 2019-03-26
• Status Verified: 2022-10
• Last Update Submitted: 2022-10-28
• Last Update Posted: 2022-10-31
• Primary Completion: 2023-06-01
• Study Completion: 2024-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Biopsy or image (in the setting of hepatocellular carcinoma (HCC)) diagnosed hepatic malignancy
• Total bilirubin < 2 mg/dL
• ECOG status ≤ 2
• Life expectancy >3 months as documented in the medical record by the enrolling physician
• Age >22 years
• Lesion >2.0 cm which is amenable to percutaneously biopsied

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Exclusion Criteria

• Unwilling or unable to attend all study related follow ups
• Technetium 99 macro aggregated albumin (MAA) lung shunt fraction >20%
• Arterial anatomy which precludes the ability to safely perform RE
• INR > 1.8 or platelet count <50,000 which cannot be corrected
• Patients who are unable to hold anticoagulation and/or antiplatelet therapy in the periprocedural setting

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Yttrium-90	Yttrium-90	This single arm study is to evaluate immunologic changes following the treatment of primary or secondary malignancies of the liver utilizing beta-emitting, Yttrium-90.

Primary Outcome Measures

Name	Time	Method
Change in concentrations of PBMC	12 weeks	Determine changes in the peripheral blood lymphocytes utilizing flow cytometery after radioembolization (RE) therapy for primary and secondary malignancies of the liver at 12 weeks.

Secondary Outcome Measures

Name	Time	Method
Change in concentrations of cytokines	1, 4, 12 weeks	Determine changes in the peripheral blood cytokines after radioembolization (RE) therapy for primary and secondary malignancies of the liver. Specifically cytokines IL-1α units/mg, IL-1β units/mg, IL-2 units/mg, IL-6 units/mg, IL-10 units/mg, IL-12p70 units/mg, IL-18 units/mg, TNFα units/mg, IFN-Y units/mg, Fit ligand 3 units/mg, and MCP-1 units/mg will be measured.
Change in concentrations of immune cell infiltration into the tumor	1, 4, 12 weeks	Determine the changes in infiltrating immune cells within the treated tumor, which occur after radioembolization (RE) therapy for primary and secondary malignancies of the liver. This will be accomplished by obtaining tissue samples of the treated tumor before and after treatment, then performing staining and cell counts to determine the change in cytotoxic t cells, t helper cells, natural kill cells, macrophages, and dendritic cells.
Change in concentrations of PBMC	1 and 4 weeks	Determine changes in the peripheral blood lymphocytes utilizing flow cytometery after radioembolization (RE) therapy for primary and secondary malignancies of the liver at 1 and 4 weeks.

Trial Locations

Locations (1)

University of Minnesota; 🇺🇸 Minneapolis, Minnesota, United States