A prospective, multicenter, open-label, single-arm clinical trial design to evaluate the safety and efficacy of 90Y resin microspheres for the treatment of unresectable HCC: the DOORwaY90 (Duration Of Objective Response with arterial Ytrrium-90) study

Armeen Mahvash, Steven Chartier, Mark Turco, Paula Habib, Steven Griffith, Scott Brown, S Cheenu Kappadath, Armeen Mahvash, Steven Chartier, Mark Turco, Paula Habib, Steven Griffith, Scott Brown, S Cheenu Kappadath

Abstract

Background: Selective internal radiation therapy (SIRT) with yttrium-90 (90Y) resin microspheres is an established locoregional treatment option for unresectable hepatocellular carcinoma (HCC), which delivers a lethal dose of radiation to hepatic tumors, while sparing surrounding healthy tissue. DOORwaY90 is a prospective, multicenter, open-label, single arm study, designed to evaluate the safety and effectiveness of 90Y resin microspheres as first-line treatment in patients with unresectable/unablatable HCC. It is unique in that it is the first study with resin microspheres to utilize a personalized 90Y dosimetry approach, and independent review for treatment planning and response assessment.

Methods: Eligibility criteria include unresectable/unablatable HCC, Barcelona Clinic Liver Cancer stage A, B1, B2, or C with a maximal single tumor diameter of ≤ 8 cm, and a sum of maximal tumor diameters of ≤ 12 cm, and at least one tumor ≥ 2 cm (long axis) per localized, modified Response Evaluation Criteria in Solid Tumors. Partition model dosimetry is used to determine the optimal dose; the target mean dose to tumor is ≥ 150 Gy. Patients are assessed at baseline and at regular intervals up until 12 months of treatment for response rates, safety, and quality of life (QoL). Post-treatment dosimetry is used to assess dose delivered to tumor and consider if retreatment is necessary. The co-primary endpoints are best objective response rate and duration of response. Secondary endpoints include grade ≥ 3 toxicity, QoL, and incidence of liver resection and transplantation post SIRT. Target recruitment is 100 patients.

Discussion: The results of this trial should provide further information on the potential use of SIRT with 90Y resin microspheres as first-line therapy for unresectable HCC.

Trial registration: Clinicaltrials.gov; NCT04736121; date of 1st registration, January 27, 2021, https://ichgcp.net/clinical-trials-registry/NCT04736121 .

Keywords: 90Y resin microspheres; Hepatocellular carcinoma (HCC); Radioembolization; SIRT.

Conflict of interest statement

AM has acted as a consultant and received research support from Sirtex, BTG/Boston Scientific, Siemens Healthineers and ABK Biomedical. SC, MT, PH, and SG are employees of Sirtex Medical. SB is an employee of Bright Research Partners and has acted as a consultant to Sirtex. SCK has acted as a consultant to Sirtex and ABK Medical, and has received research support from Boston Scientific, ABK Biomedical and GE Healthcare.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study flow diagram

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