A Pilot Study For Patients Receiving Radiation Therapy for Liver Cancer

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the role of quantitative MR imaging and blood-based biomarkers to measure liver function in patients receiving radiation therapy for liver cancer or cancer that has spread to the liver.

Detailed Description
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The purpose of this study is to evaluate the role of quantitative MR imaging and blood-based biomarkers to measure liver function in patients receiving radiation therapy for liver cancer or cancer that has spread to the liver. The feasibility of using MR imaging to monitor liver function at baseline and following liver radiation therapy will be determined. Information from MR images and blood samples, along with patient questionnaires, will be used.

Official Title
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Pilot Study to Assess the Role of Blood-based Biomarkers and Quantitative MR Imaging

Conditions
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Cancer, Hepatocellular, Radiotherapy Side Effect

Intervention / Treatment
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* Device: Multiparametric MRI scans
* Device: Multiparametric MRI scans + HepQuantShunt Test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has the psychological ability and general health needed to provide informed consent, completion of study requirements, and required follow-up Patient provides study-specific informed consent prior to study entry All primary histologies (Hepatocellular carcinoma or Cholangiocarcinoma) as well as hepatic metastases are eligible Prior history of radiation therapy (external beam or radioembolization) is allowed, with no limit to the number of prior courses of radiation therapy Any number of lesions (with no size limit) of pathologically documented (histologically or cytologically) or radiographically proven tumor/metastasis that are being targeted Prior history of chemotherapy, immunotherapy, or targeted biological therapy is allowed Concurrent enrollment on other prospective registry or treatment intention trials is allowed Exclusion Criteria: Pregnant or breast-feeding females Subjects with history of claustrophobia impacting ability to perform MRI during the study Subjects who fulfill any of the contraindications for MRI; examples include any ferromagnetic material, any metallic shrapnel or fragments or implanted electronic devices contained within the body or metal-containing tattoos Unable to participate in MR assessments due to physical limitations of equipment tolerances (MRI bore size and/or weight limit) Any person unable to lie still within the environment of the MRI scanner or maintain a breath hold for the required period to acquire images Exclusion criteria for HepQuant SHUNT testing ONLY: Known history or suspected hypersensitivity to human serum albumin, or its preparations Subjects with extensive resection of large segments of small intestine (short gut) or severe gastroparesis Subjects on either a non-selective beta blocker (propranolol, nadolol) or an angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) who are unwilling or unable to delay taking their normal dose the morning of their testing Subjects who are allergic to any ingredient in the formulations or components in the HepQuant SHUNT kit including human serum albumin (HSA) or cholate compounds (theoretical - none yet reported) Subjects unwilling or unable to fast for at least 5 hours. Fasting means no intake of food or food supplements, including fiber preparations or biosimilars; or, any preparations or resins (cholestyramine, colestipol, colesalvalem) that might act within the gut lumen to bind the orally administered d4-cholate in the HepQuant test

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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Multiparametric MRI scan group<br>Multiparametric MRI scans will be used to evaluate baseline degree of liver fibroinflammation and function as well as temporal changes in liver fibroinflammation and function using MRI-based LiverMultiScan software. | Device: Multiparametric MRI scans<br>* Multiparametric MRI scans will be used to evaluate baseline degree of liver fibroinflammation and function as well as temporal changes in liver fibroinflammation and function using MRI-based LiverMultiScan software. We will also measure liver function using HepQuant SHUNT test in a subset of patients enrolled in this study.<br>|
| Experimental: Multiparametric MRI scans + HepQuantShunt Test group<br>Eligible patients can have previously undergone any modality and number of prior treatments for their hepatic malignancies, must be considered for either liver photon or proton radiation in the de-novo or re-irradiation setting and can be simultaneously enrolled on parallel trials. | Device: Multiparametric MRI scans<br>* Multiparametric MRI scans will be used to evaluate baseline degree of liver fibroinflammation and function as well as temporal changes in liver fibroinflammation and function using MRI-based LiverMultiScan software. We will also measure liver function using HepQuant SHUNT test in a subset of patients enrolled in this study.<br>Device: Multiparametric MRI scans + HepQuantShunt Test<br>* Eligible patients can have previously undergone any modality and number of prior treatments for their hepatic malignancies, must be considered for either liver photon or proton radiation in the de-novo or re-irradiation setting and can be simultaneously enrolled on parallel trials. Patients must not have any contraindications that would preclude MRI imaging or receipt of HepQuant SHUNT test for those agreeable to have HepQuant SHUNT test.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of Quantitative Multiparametric MRI | Feasibility will be determined by assessing the percentage of patients who complete at least two quantitative multiparametric MRI scans after study enrollment. The feasibility endpoint will be presented as proportions and a Clopper Pearson 95% exact confidence interval will be determined. | Up to 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Disease Severity Index (DSI) scores | Change in DSI scores from baseline will be evaluated using HepQuant SHUNT testing. The HepQuant SHUNT test measures hepatocyte function using the Disease Severity Index (DSI). Increased DSI scores have been correlated with worsening liver function and disease severity and progression and response to treatments. The DSI calculation is proprietary; however, the test generates a liver DSI score ranging from 0 (no hepatic impairment) to 50 (severe hepatic impairment) that is a composite of both hepatic filtration rates and correlates with stage of fibrosis, presence of varices, and risk for future clinical outcomes. Raw changes in DSI scoring from baseline scores will be summarized using descriptive statistics and will be examined using a paired t-test or Wilcoxon Sign rank test. | Baseline and 3 months post-RT | 
| Ability of LiverMultiScan™ MRI software to predict the risk of non-classic radiation-induced liver disease (RILD) by measuring the pre-RT liver health assessment score | The ability of LiverMultiScan to predict the risk of non-classic RILD will be evaluated. The pre-radiotherapy liver health assessment score will be calculated by measuring the Future Liver Remnant volume outside the 50% radiation isodose line weighted by the liver cT1 value. MRI images will be post-processed using LiverMultiScan, which provides a multiparametric quantitative map of a region of interest in the liver including characterization of the underlying liver fibroinflammation as reported by a corrected T1 (cT1) value, which will be measured and reported in milliseconds (ms). The likelihood of non-classic RILD based on the cT1 value will be assessed using multivariable logistic regression. Non-classic RILD is defined as either worsening of Child-Pugh Score by >=2 points (overall range: 5-15 points) at 6 months following RT or an elevated aminotransferase (ALT or AST) level > 5 times the upper limit of normal or baseline value within 90 days of completion of RT. | Baseline to 6 Months post-RT | 
| Change in Total Liver Volume and Volume of non-irradiated and irradiated lobes | Change in total liver volume, as well as volume of non-irradiated and irradiated liver lobes, from pre-radiotherapy treatment at baseline will be evaluated using Gd-EOB-DTPA enhanced MRI of the abdomen at the specified timeframes to assess the impact of radiotherapy. Mean changes in total liver volume (cm^3) and volume of non-irradiated and irradiate lobes will be assessed using the MRI software image analysis and summarized by study arm. The data will be analyzed using linear mixed-effects models. Increases in liver volume are correlated to more favorable outcomes | Baseline and 3, 6, 9, and 12 Months post-RT |