Combined Y-90 Selective Internal Radiation Therapy (Y-90 SIRT) and Stereotactic Body Radiation Therapy (SBRT) in Hepatic Malignancy.

Study Overview
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Brief Summary
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This study will investigate the combination of Ytrium-90 (Y-90) Selective Internal Radiation Therapy (SIRT) followed by Stereotactic Body Radiation Therapy (SBRT). Y-90 SIRT alone or SBRT alone are standard procedures used in the treatment of liver cancer. This study will assess the combination of Y-90 SIRT and SBRT and obtain preliminary information about the side effects and safety of the combination therapy. Additionally, this is the first time that Y-90 PET-CT imaging will be included in planning for SBRT.

Detailed Description
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Selective Internal Radiation Therapy (SIRT) is a technique where radiation is internally delivered to a tumor. In SIRT, small radioactive beads are deposited in the liver through a large blood vessel (hepatic artery). SIRT that uses the radioactive material Yttrium-90 is called Y-90 SIRT. Stereotactic Body Radiation Therapy (SBRT) is a technique where radiation is externally delivered to a tumor. In SBRT, a machine produces a beam of radiation that targets the tumor from outside the body. After receiving Y-90 SIRT, participants will be evaluated to estimate how much radiation was absorbed by their tumors during Y-90 SIRT. Y-90 PET-CT imaging will be used to help plan SBRT, which will target areas of tumors that did not receive as much radiation as expected during Y-90 SIRT. Since patients treated with Y-90 for any liver malignancy can benefit from the Y-90+SBRT combined treatment approach we have decided to open up the protocol to all eligible patients and not HCC alone.

Official Title
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A Phase 1 Study of Combined Y-90 Selective Internal Radiation Therapy (Y-90 SIRT) and Stereotactic Body Radiation Therapy (SBRT) in Hepatic Malignancy.

Conditions
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Liver Malignancy

Intervention / Treatment
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* Drug: Yttrium-90
* Device: Selective Internal Radiation Therapy
* Radiation: Stereotactic Body Radiation Therapy
* Diagnostic Test: PET/CT
* Device: Therasphere


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of unresectable hepatocellular carcinoma or metastatic liver cancer. Hepatocellular carcinoma is defined as having at least one of the following: Biopsy proven hepatocellular carcinoma (HCC); or A discrete hepatic tumor(s) as defined by the Barcelona imaging criteria. Metastatic liver cancer is defined as having: o pathological confirmation of any metastatic disease with a new or enlarging liver lesion consistent with metastases. The targeted lesion does not need to be biopsied if the patient has a known history of metastatic disease Patients must not have known untreated or progressive disease outside of the liver At least one lesion >2 cm diameter or 4 cc volume Patients must have a life expectancy of at least 6 months. Patients must be 18 years of age or older All men, as well as women of childbearing potential, must agree to use effective contraception throughout the study and for 90 days following treatment. Patients must understand and be willing to sign an informed consent form approved for this purpose by the Institutional Review Board (IRB) of the University of Michigan Medical Center indicating that they are aware of the investigational aspects of the treatment and the potential risks. Exclusion Criteria: Inability to lie still for imaging studies (e.g. PET/CT) Pregnancy or nursing females or refusal to use birth control in patients capable of reproduction. Patients with known allergy or contraindication to intravenous iodinated contrast agents Patients with an allergy or contraindication to MRI on MRI contrast (Eovist or Gadolinium) Contraindication to Theraspheres Tc-99m macroaggregated albumin (MAA) hepatic arterial perfusion scintigraphy showing any deposition to the gastrointestinal tract that may not be corrected by angiographic techniques Shunting of blood to the lungs that could result in delivery of greater than 30 Gy to the lungs. Hepatic artery catheterization contraindication; such as patients with vascular abnormalities or bleeding diathesis; Bilirubin >2.0 at baseline Occlusion of the main portal vein Contraindication to radiation therapy Note: Patients who have an increase in bilirubin >1.0 from the time of Y90 to SBRT or his/her bilirubin goes above 2.5 after Y90 will not be eligible for SBRT.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Y-90 SIRT followed by SBRT<br>Y-90 SIRT followed by SBRT | Drug: Yttrium-90<br>* Radioactive isotope Y-90 at day 0, administered by selective internal radiation therapy (SIRT)<br>* Other names: Y-90;Device: Selective Internal Radiation Therapy<br>* SIRT at day 0, to administer Yttrium-90 (Y-90) Theraspheres<br>* Other names: SIRT;Radiation: Stereotactic Body Radiation Therapy<br>* 3-5 fractions over 1-2 weeks, after Y-90 SIRT<br>* Other names: SBRT;Diagnostic Test: PET/CT<br>* Within 3 hours of completing Y-90 SIRT<br>Device: Therasphere<br>* Glass microspheres containing Y-90, administered at day 0 by SIRT<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Child-Turcotte-Pugh (CTP) score >= 2 points from baseline | The primary safety endpoint is the binary indicator for a CTP increase of 2 or more points within 6 months and relative to pre-SBRT baseline. An increase of 2 or more points indicates clinically significant liver decompensation. | Up to 6 months after SBRT | 
| Incidence of toxicities of grade 3 or higher | A secondary safety endpoint is grade 3+ toxicity within 6 months relative to pre-SBRT baseline. Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. | Up to 6 months after SBRT | 
| Number of patients with a change in albumin + bilirubin (ALBI) level of >= 0.5 | A secondary safety endpoint is the binary indicator for an increase in ALBI within 6 months relative to pre-SBRT baseline of 0.5 or greater. | Up to 6 months after SBRT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Freedom from local progression (FFLP) at the lesion level | FFLP at the lesion level is defined as the time from SIRT to progression of a SBRT-treated lesion. Progression is defined based on RECIST and mRECIST criteria. | Until progression or last surveillance scan at approximately 24 months after SBRT | 
| Freedom from local progression (FFLP) at patient level | FFLP at the patient level is defined as the time from SIRT to progression of the treated lesions including those not targeted by SBRT. Progression is defined based on RECIST v1.1and mRECIST criteria. | Until progression or last surveillance scan at approximately 24 months after SBRT | 
| Response rate | Response rate defined per RECIST v1.1 and mRECIST criteria and categorized as follows: progressive disease or stable disease = non-responder, partial response or complete response = responder. | Up to 6 months after SBRT | 
| Overall survival | Overall survival will be calculated as the time from Y-90 SIRT treatment to death from any cause, or until patient's last follow-up visit, or until study stops. | Until death from any cause, or until patient's last follow-up visit, or until study stops; up to approximately 5 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ytrium-90 (Y-90), Selective Internal Radiation Therapy (SIRT), Stereotactic Body Radiation Therapy (SBRT)