Y-90 Versus SBRT for Inoperable HCC

Study Overview
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Brief Summary
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This phase II trial tests whether Y-90 segmentectomy (internal radiation) versus stereotactic body radiation therapy (external radiation) is more optimal in treating inoperable liver cancer. Y-90 segmentectomy consists into very tiny radioactive glass beads that can be injected into the liver through the blood vessels supplying the liver. Stereotactic body radiation therapy uses special equipment to position a patient and deliver external radiation to tumors with high precision. This study many help doctors determine which treatment, Y-90 segmentectomy or SBRT, works better in treating liver cancer.

Detailed Description
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PRIMARY OBJECTIVE: I. Determine feasibility of trial enrollment (enrollment date). SECONDARY OBJECTIVE: I. To assess differences in overall survival, local control, time to intrahepatic progression, time to next treatment, rate of liver transplant, toxicity, and patient reported complications and quality of life. EXPLORATORY OBJECTIVE: I. Compare cumulative cost of treatment-related medical care at 13 months. OUTLINE: Patients will be randomized in 1 of 2 arms. Arm I: Patients undergo SBRT every other day for a total of 5 days over 2 weeks. Arm II: Patients receive Y-90 radioembolization via injection on day 1. After completion of study, patients are followed up at 2, 4, and 12 weeks and then every 3 months for 13 months.

Official Title
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Randomized Prospective Two-Arm Feasibility Trial of Stereotactic Body Radiation Therapy Versus Yttrium-90 Segmentectomy in Inoperable Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma, Stage I Hepatocellular Carcinoma AJCC v8, Stage IA Hepatocellular Carcinoma AJCC v8, Stage IB Hepatocellular Carcinoma AJCC v8, Stage II Hepatocellular Carcinoma AJCC v8, Stage III Hepatocellular Carcinoma AJCC v8, Stage IIIA Hepatocellular Carcinoma AJCC v8, Stage IIIB Hepatocellular Carcinoma AJCC v8, Stage IVA Hepatocellular Carcinoma AJCC v8

Intervention / Treatment
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* Other: Quality of Life
* Other: Questionnaire Administration
* Radiation: Stereotactic Body Radiation Therapy
* Procedure: Yttrium-90 Microsphere Radioembolization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and the willingness to sign a written informed consent document. Age >= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included. Patient with non-metastatic hepatocellular carcinoma (HCC) including lesion(s) amenable to definitive therapy with either SBRT or Y-90 segmentectomy, limited to =< 2 liver segments, as agreed upon by the multidisciplinary tumor board consensus. Patient not otherwise optimal candidates for resection or thermal ablation, as agreed upon by the multidisciplinary tumor board. Have a Child-Pugh criteria (CP) score B7 or better. Eastern Clinical Oncology Group (ECOG) performance status =< 1, or Karnofsky performance scale > 70. No other prior invasive malignancy is allowed except for the following: adequately treated basal or squamous cell skin cancer, in situ breast or cervical cancer. Stage I or II invasive cancer treated with a curative intent without evidence of disease recurrence for at least five years. Exclusion Criteria: Participant is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, serious or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring adverse events (AEs) or compromise the ability of the patient to give written informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Device Feasibility
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (SBRT)<br>Patients undergo SBRT every other day for a total of 5 days over 2 weeks. | Other: Quality of Life<br>* Ancillary studies<br>* Other names: Quality-of-Life;Other: Questionnaire Administration<br>* Ancillary studies<br>Radiation: Stereotactic Body Radiation Therapy<br>* Undergo SBRT<br>* Other names: Stereotactic Ablative Body Radiation Therapy;|
| Experimental: Arm II (Y-90 radioembolization)<br>Patients receive Y-90 radioembolization via injection on day 1. | Other: Quality of Life<br>* Ancillary studies<br>* Other names: Quality-of-Life;Other: Questionnaire Administration<br>* Ancillary studies<br>Procedure: Yttrium-90 Microsphere Radioembolization<br>* Given via injection<br>* Other names: Yttrium-90 Radioembolization;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of enrollment (enrollment rate) | Determine feasibility of trial enrollment for two therapeutic groups. | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Death, adjuvant systemic therapy or liver directed therapy to treated lesion, transplant, lost to follow up, or 13 months post-treatment | 
| Time to progression |  | Time of radiographic evidence of treated tumor progression as determined by tumor board review, adjuvant systemic therapy or liver directed therapy to treated lesion, transplant, death, or 13 months post-treatment | 
| Time to intrahepatic progression |  | Time of radiographic intrahepatic progression, adjuvant systemic therapy or liver directed therapy, transplant, death, or 13 months post-treatment | 
| Rate of liver transplant |  | Time of liver transplant, death, or 13 months post-treatment | 
| Rate of non-classic radiation induced liver disease | Defined as a Child-Pugh criteria >= 2 point increase. | Up to 13 months | 
| Rate of patient reported outcome-Common Terminology Criteria for Adverse Events |  | Baseline up to 13 months | 
| Change in patient reported quality of life | Measured by Functional Assessment of Cancer Therapy-Hepatobilliary Cancer compared to baseline. | Baseline to 13 months | 
| Time to next treatment |  | Time to next liver directed or non-adjuvant systemic therapy, transplant, or death, assessed up to 13 months |