TheraSphere® For Treatment of Metastases in Liver

Feasibility of a Personalized Dosimetry-based Treatment Planning for Radioembolization in the Treatment of Unresectable Colorectal Metastases in Liver

To investigate whether the dose predicted by pre-therapy 99mTc MAA SPECT predicts the dose to the liver from the 90Y microspheres as assessed by post-therapy 90Y SPECT/CT or positron emission tomography (PET)/CT.

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer; Colorectal Cancer Metastatic
• Intervention / Treatment: Other: Therasphere Therapy

Detailed Description

This study will acquire imaging information from 3-5 patients that will demonstrate feasibility of future implementation of personal dosimetry-based treatment planning for Trans-arterial Radio-embolization (TARE).

TARE therapy of liver neoplasia using 90Y-theraspheres has a long history. The device is FDA approved for the treatment of hepatocellular carcinoma, but has been used extensively for treatment of secondary liver neoplasia, including metastatic colorectal lesions under Humanitarian Device Exemption protocols such as this one.

As a targeted radioactive therapy, the current TARE implementation suffers from a lack of efficiency characteristic of radiopharmaceutical therapy (RPT) in general; namely, that the activity determined to treat the patient is not optimized according to normal organ tolerated absorbed dose and tumor efficacy thresholds. The amount of activity to be administered is determined from volumetrics established from associated imaging, either MRI or X-ray CT, where the total volume of irradiated tissue is considered as irrigated by the artery selected for administration, including both tumor and normal organ tissue. From this volume determination, the activity necessary to deliver an average pre-determined safe absorbed dose (120 Gy) to the entire irradiated region is calculated and administered.

In RPT, in the theranostic paradigm, a pre-therapeutic, or surrogate, quantity of activity is administered to the patient; 3D imaging (SPECT/CT or PET/CT) is then acquired at several time points and the individual patient's pharmacokinetics are determined, the normal organ and tumor dosimetry are performed and the optimal administered activity calculated that will deliver safe and efficacious treatment for the individual patient is determined, generally limited by the normal organ at risk maximum tolerated dose.

TARE presents a number of unique characteristics that enable a simpler version of this approach than is typical for most RPT. The method of administration means that only the normal liver and lungs need to be considered as potential organs at risk as the microspheres embolize and do not circulate systemically; the lack of associated photons in the 90Y decay chain means that a simple activity-to-dose-rate conversion can be used; the embolization means that only a single imaging time point is necessary as there is no redistribution of activity over time and the dose rate is converted to absorbed dose using the physical decay parameters of 90Y. These natural simplifications are already exploited in the current volumetric paradigm, where a 99mTc-macro albumin aggregate (MAA) surrogate and planar imaging are used to determine the fraction of total activity that is shunted to the lung and where a derived conversion factor is used to convert activity to absorbed dose.

The technical complication in TARE is that the surrogate (99mTc-MAA) has a different nature from the therapeutic device (90Y-theraspheres), and thus the reliability of the predictive quality of the surrogate is disputed. However, with precise and advanced imaging reconstruction and dosimetry the investigators have shown the ability to accurately and precisely predict normal liver and tumor average 90Y-therasphere uptake and absorbed dose from 99mTc-MAA.

This protocol seeks to acquire the imaging information from 3-5 patients that will demonstrate feasibility of future implementation of personal dosimetry-based treatment planning for TARE. In addition to the clinical standard of care assessments: 1. a single SPECT/CT instead of the current planar image will be acquired of the surrogate 99mTc-MAA; 2. An additional single 3D image (either SPECT/CT or PET/CT, depending on machine availability) will be acquired up to 6 hours post-administration of the therapeutic 90Y-microspheres for comparison. Informed consent will be obtained.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• The Diagnosis of metastatic colorectal cancer to the liver
• Patients with a diagnosis of metastatic colorectal cancer to the liver
• Liver metastases are unresectable
• Tumors are hypervascular based on visual estimation by the Investigator
• Target tumors are measurable using standard imaging techniques
• Performance Status Score 0 - 2
• Age ≥18 years
• Life expectancy ≥3 months
• >4 weeks since prior radiation, surgery or chemotherapy
• Able to comprehend and provide written informed consent in accordance with institutional and federal guidelines
• At least one month has elapsed since most recent prior cancer therapy with the following exception:
• Patient is willing to participate in the study and has signed the study informed consent

Exclusion Criteria:

Patients may not be treated with TheraSphere® if patients have any of the following exclusions:

• Any pre-treatment laboratory findings within 15 days of treatment demonstrating liver dysfunction:
• Blood test result levels outside of the normal range
• Any history of hepatic encephalopathy
• Any contraindications to angiography and hepatic artery catheterization such as:
• History of severe allergy or intolerance to any contrast media, narcotics, sedatives or atropine that cannot be corrected or premedicated
• Bleeding diathesis, not correctable by usual forms of therapy
• Severe peripheral vascular disease that would preclude catheterization.
• Evidence of pulmonary insufficiency
• Significant extrahepatic disease representing an imminent life-threatening outcome
• Active uncontrolled infection
• Significant underlying medical or psychiatric illness
• Co-morbid disease or condition that would preclude safe delivery of TheraSphere® treatment or, in the judgment of the physician, place the patient at undue risk
• Pregnancy
• Special Categories of Patients: Not applicable
• Research in Mentally Disabled People: No. All participants or legal guardians will be fully able to give informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• 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: Therasphere Therapy; All participants will receive the Therasphere Therapy.	Other: Therasphere Therapy; TheraSphere is a radiotherapy treatment for primary and secondary liver neoplasia. This is an imaging study that will examine 3-5 patients who have been treated for metastatic colorectal cancer in the liver using TheraSphere®. Participation in the study involves an additional post-treatment SPECT/CT or PET/CT scan at (0-6) hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients That Met the Criterion That the Dose Estimated With Tc-99m MAA SPECT Was Within 15% of the Dose Estimated From Y-90 SPECT	Change in dose estimates of radioactivity from Therasphere treatment to liver tumor target, measured in Gray, will be compared at pre-treatment and up to 6 hours post-treatment. Reported as number of patients that met the criterion that the dose estimated with Tc-99m MAA SPECT was within 15% of the dose estimated from Y-90 SPECT	Pre-Treatment and up to 6 hours Post-Treatment

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Robert Hobbs, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): November 12, 2020
• Primary Completion (Actual): September 1, 2021
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: August 14, 2020
• First Submitted That Met QC Criteria: August 14, 2020
• First Posted (Actual): August 18, 2020

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: J2006; National Institute Of Health (Other Grant/Funding Number: HHSN267152N0911701090C3070C047)

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No