Clinical trial NCT02966223: A Study to Assess the Effect of Y-90 Therapy on Non-target/Background Liver
Official title: A Study to Assess the Effect of Y-90 Therapy on Non-target/Background Liver
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: HCC
Liver Cancer
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: BTG International Inc.
First posted: 2016-11-17
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The primary question of interest is quantifying the relationship between Y-90 liver therapy and liver damage. Little is known on this subject. Present assumptions and calculations of Y-90 administration are based on surgical lobar hepatectomies and external radiation beam therapies. The investigators hope that by using a functional model of the liver, the investigators can improve this important knowledge gap.

The investigators will be enrolling patients planning to receive Y-90 therapy for the treatment of liver malignancies. The diagnosis of a primary liver cancer, hepatocellular carcinoma (HCC), is usually made by a combination of specific imaging findings and clinical criteria; only rarely is a confirmatory biopsy performed. This is due to the high accuracy of the present diagnostic model and the significant risk of biopsy and tumor seeding.

Y-90 therapy involves administering radioactive particles to liver tumors by placing a catheter in a hepatic artery supplying the tumor using angiographic techniques and injection of these particles.

Y-90 Positron Emission Tomography-Computed Tomography (PET/CT) imaging has been established as a method to validate and quantitate distribution of Yttrium after Y-90 administration. The post Y-90 therapy PET/CT images provide an imaging distribution of the Y-90, which is essential for validation of administered versus planned dose to the liver lesion and background liver.

If the investigators can compare the Y-90 distribution to estimate background liver radiation distribution and dose (generated by the Y-90 PET/CT scan) combined with the global and regional function map (generated by the hepatobiliary \[HIDA\] scan performed before and after therapy), then the investigators will be assuming that the difference pre and post therapy in global and regional function can be ascribed to the Y-90 administration. The investigators will also analyze the Magnetic Resonance Imaging (MRI) and CT sets performed before and after therapy and correlate the imaging results collected with clinical findings such as ascites/encephalopathy and routine serological markers (bilirubin, albumin, International normalized ratio \[INR\], etc.). With this information, the investigators will have the potential to establish whether there is a relationship between Y-90 distribution to non-tumoral (normal) hepatic parenchyma and the incidence and severity of Radioembolization-Induced Liver Disease (REILD). This would have the potential to improve selection criteria and outcomes in populations selected for Y-90 therapy in the future.

Detailed description: Little is known on the potential relationship between Y-90 liver therapy and liver damage this subject. Present assumptions and calculations of Y-90 administration are based on surgical lobar hepatectomies and external radiation beam therapies.

As most participants that need Y90 based liver therapies have compromised livers, the importance of knowing what potential collateral liver damage could be induced by Y90 is key so as not induce liver failure. Successful treatment of a liver malignancy would not be important if the potential mortality/morbidity risk of the treatment is higher or equal to the existing malignancy.

As apposed to anatomical imaging looking for changes in size/shape which are late changes, the investigators hope that by using a functional model of the liver, which can show early changes of liver damage, the investigators can improve the sensitivity for detection of liver damage and bridge this important knowledge gap. Additionally due to compensatory hypertrophy of the non treated liver, potential liver damage estimated by lab tests may be masked, again this emphasizes the importance of the measurement of the functional approach before and after therapy.

The investigators will be enrolling participants planning to receive Y-90 therapy for the treatment of liver malignancies. The diagnosis of a primary liver cancer, hepatocellular carcinoma (HCC), is usually made by a combination of specific imaging findings and clinical criteria; only rarely is a confirmatory biopsy performed. This is due to the high accuracy of the present diagnostic model and the significant risk of biopsy and tumor seeding.

Y-90 therapy involves administering radioactive particles to liver tumors by placing a catheter in a hepatic artery supplying the tumor using angiographic techniques and injection of these particles.

Y-90 PET/CT imaging has been established as a method to validate and quantitate distribution of Yttrium after Y-90 administration. The post Y-90 therapy PET/CT images provide an imaging distribution of the Y-90, which is essential for validation of administered versus planned dose to the liver lesion and background liver.

The investigators will be performing both specialized nuclear medicine HIDA and MRI scans aimed at constructing a functional map of the liver before and 3 months after therapy.

The investigators will compare the Y-90 distribution to estimate background liver radiation distribution and dose (generated by the Y-90 PET/CT scan) combined with the global and regional function map (generated by the HIDA and MRI scans performed before and after therapy), then the investigators will be assuming that the difference pre and post therapy in global and regional function can be ascribed to the Y-90 administration.

The investigators will also analyze the MRI and NM data sets performed before and after therapy and correlate the imaging results collected with clinical findings such as ascites/encephalopathy and routine serological markers (bilirubin, albumin, INR, etc.).

With this information, the investigators will have the potential to establish whether there is a relationship between Y-90 distribution to non-tumoral (normal) hepatic parenchyma and the incidence and severity of REILD. This would have the potential to improve selection criteria and outcomes in populations selected for Y-90 therapy in the future.

Eligibility criteria: Inclusion Criteria:

1. Subjects must have the ability to understand and the willingness to sign a written informed consent document.
2. Subjects must be ≥ 18 years of age at the time of signing informed consent.
3. Subjects must have a diagnosis of hepatocellular carcinoma (HCC) and a treatment plan to undergo radioembolization therapy with Y-90 at Indiana University Health Hospital.
4. Subjects must be willing and able to comply with all procedures and visits required for this protocol (pre-treatment, during treatment, and post-treatment).

Exclusion Criteria:

1. Subjects who have contraindications for receiving Y-90 therapy and any routine procedures and imaging associated with Y-90 therapy, including subjects who are pregnant or are planning to become pregnant, will not be eligible to participate in this study. Female subjects who are of childbearing potential should inform her treating physician should she become pregnant at any time during the course of the study.
2. Subjects with contraindications for receiving hepatobiliary scans (HIDA scans) and Magnetic Resonance Imaging (MRI scans) will not be eligible to participate in this study.

Primary outcomes:
measure: Primary
timeFrame: 3 months
Secondary outcomes:
measure: Secondary
timeFrame: 3 months
measure: Secondary
timeFrame: 6 months
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Hospital
state: Indiana
Study officials:
affiliation: Indiana University
name: Mark Tann, MD
role: PRINCIPAL_INVESTIGATOR
References: