Low-dose Y90 Treatment Planning for HCC

Not Applicable

Completed

• Conditions: Cancer; Cancer of Liver; HCC
• Interventions: Device: SIR-Spheres microspheres

• Registration Number: NCT04172714
• Lead Sponsor: Emory University

Brief Summary

The study proposes low-dose Y90 microspheres for therapy planning of HCC, as an alternative to Technetium (99mTc) albumin aggregated (MAA), to be a bioidentical therapeutic Y90 surrogate marker to better predict and thus achieve optimal therapeutic dosing.

Detailed Description

Hepatocellular carcinoma is a second deadliest cancer in the world with less than 20% of patients eligible for curative surgery at the time of diagnosis. Yttrium-90 (Y90) radioembolization is palliative treatment with promising result. However, one of the most important factors in the success of Y90 treatment is to ensure adequate dose of radioactive material is delivered to the tumor. The technetium-99 macroaggregated albumin (MAA) which is currently used for Y90 treatment planning and shunt study does not predict distribution of Y90 in the lungs, tumors, and liver. Therefore, accurate and personalized treatment planning cannot be performed using MAA. In this study, we are proposing using low-dose Y90 microspheres for the planning stage of the therapy to obtain an accurate estimation of distribution of Y90 therapy dose. This will in turn allow us to ensure adequate dose of Y90 is delivered to the tumor(s) while minimizing dose delivered to non-tumor liver and lungs in order to decrease the chance of treatment related toxicity to the liver and lungs.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2019-11-20
• Study First Submitted QC: 2019-11-20
• Study First Posted: 2019-11-21
• Study Start: 2019-12-16
• Primary Completion: 2021-06-30
• Study Completion: 2021-06-30
• Disposition First Submitted: 2022-05-25
• Results First Submitted: 2022-08-26
• Status Verified: 2022-11
• Results First Submitted QC: 2022-11-14
• Disposition First Submitted QC: 2022-11-14
• Last Update Submitted: 2022-11-14
• Results First Posted: 2022-12-06
• Disposition First Posted: 2022-12-06
• Last Update Posted: 2022-12-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Adults ≥ 18 years
2. Life expectancy of 6 months or more as determined by the investigator
3. HCC confirmed by Liver Reporting & Data System (LIRADS) on MRI or CT
4. Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
5. ≤3 lesions
6. Longest dimension of the largest lesion ≤7cm
7. Single lobe disease
8. No significant extrahepatic metastatic disease
9. Barcelona Clinic Liver Cancer Stage A, B or C
10. ECOG < 2 (Appendix A)
11. Lesion(s) <50% of liver volume
12. Bilirubin ≤ 2 mg/dL
13. Albumin ≥ 3 g/dL
14. PT/INR < 2
15. AST/ALT ≤ 3 institutional upper limit of normal (ULN)
16. Platelet count > 50,000/mcL
17. Lung shunt fraction of <20% by planar MAA if dose modification results in inadequate dose delivered to the tumor(s)
18. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
19. Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥ 12 week before the start of study therapy. Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions.

u. Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation. v. The effects of Y90 microspheres on the developing human fetus are unknown. For this reason female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy. Winship Protocol #: RAD4784 Version Date: Aug 22, 2019 20 | P a g e w. FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of [IND Agent] administration. A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months

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Exclusion Criteria

• An individual who does not meet all the inclusion criteria in section.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Second mapping with low-dose Y90	SIR-Spheres microspheres	Patients will undergo standard of care mapping study with 99TC-MAA to plan for Y90 radioembolization therapy. Additionally,non-standard of care, intervention will be to do a second mapping study using SIR-spheres microspheres with low-dose Y90 (15 mCi) before the therapeutic Y90 radioembolization.

Primary Outcome Measures

Name	Time	Method
Lung Shunt Fraction (LSF) Ratio	Baseline	Y-90 radioembolization treatment requires estimating the activity shunted from the liver to the lungs, referred to as a lung shunt fraction (LSF). It is expressed in ratios, with higher ratio meaning a higher transit of Y-90 to the lungs (worse outcome) and lower ratio, lower transit of Y-90 to the lungs (better outcome).
Tumor to Normal Liver Activity Ratio (TNR)	Baseline	The ratios of the tumor-to-normal liver parenchymal radioactivity uptake count will be measured. TNR values will be calculated by dividing the mean count of the tumorous volume of interest (VOI) by the mean count of normal liver.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Tumor Response Using Imaging Modified Response Criteria in Solid Tumors (m-RECIST) Post Y90 Embolization	6 months post intervention	To identify tumor dose response threshold (TDRT) using Imaging Modified Response Criteria in Solid Tumors (m-RECIST), that is a method for measuring treatment response and measure of antitumor activity of cytotoxic drugs. This is measured using imaging: CT or MRI. The overall response is a combination of responses in each category: complete response (disappearance of any intramural arterial enhancement in all target lesions), partial response (at least 30% decrease in the sum of the diameters of viable target lesions), stable disease (any cases that do not qualify for either partial response or progressive disease) or progressive disease (an increase of at least 20% in the sum of the diameters of viable, enhancing target lesions, taking as a reference the smallest sum of the diameters of viable target lesions recorded since treatment started).

Trial Locations

Locations (3)

Emory University Midtown; 🇺🇸 Atlanta, Georgia, United States

Emory University Hospital; 🇺🇸 Atlanta, Georgia, United States

Emory Clinic; 🇺🇸 Atlanta, Georgia, United States