Clinical trial NCT04172714: Low-dose Y90 Treatment Planning for HCC
Official title: Theragnostic Low Dose Y90 Microspheres for Personalized Y90 Radioembolization Dosimetry Planning
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HCC
Cancer of Liver
Cancer
Keywords: Cancer
Radiation therapy
Liver Diseases
Radiology, Interventional
Radiology
Lead sponsor: Emory University
Sponsor class: OTHER
First posted: 2019-11-21
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Exclusion Criteria:

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

Primary outcomes:
measure: Lung Shunt Fraction (LSF) Ratio
timeFrame: Baseline
measure: Tumor to Normal Liver Activity Ratio (TNR)
timeFrame: Baseline
Secondary outcomes:
measure: Number of Participants With Tumor Response Using Imaging Modified Response Criteria in Solid Tumors (m-RECIST) Post Y90 Embolization
timeFrame: 6 months post intervention
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory University Midtown
state: Georgia
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University
name: Nima Kokabi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kokabi N, Webster LA, Elsayed M, Switchenko JM, Chen B, Brandon D, Galt J, Sethi I, Cristescu M, Kappadath SC, Schuster DM. Accuracy and Safety of Scout Dose Resin Yttrium-90 Microspheres for Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial. J Vasc Interv Radiol. 2022 Dec;33(12):1578-1587.e5. doi: 10.1016/j.jvir.2022.08.027. Epub 2022 Sep 6.