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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Liver Malignancy
• Intervention / Treatment: Drug: Yttrium-90; Device: Selective Internal Radiation Therapy; Radiation: Stereotactic Body Radiation Therapy; Diagnostic test: PET/CT; Device: Therasphere

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Cancer AnswerLine; Phone Number: 1-800-865-1125; Email: CancerAnswerLine@med.umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Rogel Cancer Center
      • Contact: Kyle Cuneo, MD; Phone Number: 734-355-5639; Email: kcuneo@med.umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Y-90 SIRT followed by SBRT

Drug: Yttrium-90; Radioactive isotope Y-90 at day 0, administered by selective internal radiation therapy (SIRT); Other Names: Y-90; Device: Selective Internal Radiation Therapy; SIRT at day 0, to administer Yttrium-90 (Y-90) Theraspheres; Other Names: SIRT; Radiation: Stereotactic Body Radiation Therapy; 3-5 fractions over 1-2 weeks, after Y-90 SIRT; Other Names: SBRT; Diagnostic test: PET/CT; Within 3 hours of completing Y-90 SIRT; Device: Therasphere; Glass microspheres containing Y-90, administered at day 0 by SIRT

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center
• Collaborators: Department of Health and Human Services; National Institute for Biomedical Imaging and Bioengineering (NIBIB)
• Investigators: Principal Investigator: Kyle Cuneo, MD, University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2020
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): October 16, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Stereotactic Body Radiation Therapy (SBRT); Ytrium-90 (Y-90); Selective Internal Radiation Therapy (SIRT)
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Neoplasms
• Other Study ID Numbers: UMCC 2020.052; HUM00181352 (Other Identifier: University of Michigan); R01EB022075 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes