Intra-Arterial TheraSphere Yttrium-90 Glass Microspheres in the Treatment of Patients With Unresectable Hepatocellular Carcinoma: Protocol for the STOP-HCC Phase 3 Randomized Controlled Trial

Abstract

BackgroundGlobally, hepatocellular carcinoma is the second most common cause of cancer deaths. It remains challenging to intensify cancer treatment without impairing liver function.ObjectiveThe objective of the TheraSphere in the Treatment of Patients with Unresectable Hepatocellular Carcinoma (STOP-HCC) study is to examine the hypothesis that transarterial radioembolization (TheraSphere yttrium-90 glass microspheres) combined with standard first-line treatment with sorafenib will improve outcomes over treatment with sorafenib alone in unresectable hepatocellular carcinoma. The STOP-HCC study is the largest international, multicenter, prospective study of intra-arterial treatment in combination with sorafenib in unresectable hepatocellular carcinoma. Here we report the study design.MethodsSTOP-HCC is a prospective, phase 3, open-label, randomized controlled study conducted across up to 105 sites in North America, Europe, and Asia. Eligible adults have unresectable hepatocellular carcinoma and a life expectancy of at least 12 weeks, 1 or more unidimensional measurable lesions, Child-Pugh score 7 points or less, and Eastern Cooperative Oncology Group Performance Status score 1 or lower, and are candidates for treatment with sorafenib. Presence of branch portal vein tumor thrombosis is permitted. Patients were randomly assigned in a 1:1 ratio to receive either sorafenib alone or transarterial radioembolization followed by sorafenib within 2 to 6 weeks. The primary outcome is overall survival. Secondary outcomes are time to progression, time to untreatable progression, time to symptomatic progression, tumor response, quality of life, and adverse event occurrence. The study is an adaptive trial, comprising a group-sequential design with 2 interim analyses with 520 patients, and an option to increase the sample size to 700 patients at the second interim analysis. The sample size of 520 patients allows for 417 deaths to give 80% power to detect an increase in median overall survival from 10.7 months for the sorafenib group (based on the Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol [SHARP] trial) to 14.2 months for the transarterial radioembolization+sorafenib group (hazard ratio 0.754) with 2-sided alpha of .05. The increased sample size of 700 patients allows for 564 deaths to give 80% power to detect a smaller difference in median overall survival from 10.7 months for the sorafenib group to 13.7 months for the transarterial radioembolization+sorafenib group (hazard ratio 0.781).ResultsEnrollment for the study completed in September 2017. Results of the first and second interim analyses were reviewed by the Independent Data Monitoring Committee. The recommendation of the committee, at both interim analyses, was to continue the study without any changes.ConclusionsThe STOP-HCC study will contribute toward the establishment of the role of combination therapy with transarterial radioembolization and sorafenib in the treatment of unresectable hepatocellular carcinoma with and without branch portal vein...

Advanced Stage Hepatocellular Carcinoma Successfully Treated with Transarterial Radioembolization and Multi-tyrosine Kinase Inhibitor Therapy

“…Another phase 3 prospective study, the TheraSphere in the Treatment of Patients with Unresectable Hepatocellular Carcinoma (STOP-HCC trial, NCT01556490), that comprises a larger sample size that aimed to detect a difference in the overall survival between the combined therapy and sorafenib alone therapy in unresectable HCC is ongoing, and preliminary results of the two first interim analyses support the continuation of the study. 20 Safety analyses in the SORAMIC study reported higher incidence of grade 3-4 adverse events in the combination therapy group than in the sorafenib only group. 13 Grade 2 adverse events with HFSR were developed in this case, and the patient refused further sorafenib treatment after achieving radiological CR.…”

Comparison between Y90 Radioembolization Plus Sorafenib and Y90 Radioembolization alone in the Treatment of Hepatocellular Carcinoma: A Propensity Score Analysis

“…In attendance of the results from the ongoing STOP-HCC trial, conducted by the same American group [27], our study represents the first series comparing the two treatment approaches and reporting long-term survival and progression outcomes.…”

Adaptive scan duration in SPECT: Evaluation for radioembolization

“…There are, however, also institutes where the 99m Tc‐MAA scan is used to assess the perfusion of target lesions (with potential necrotic cores) and the activity to the parenchyma. Furthermore, the potential for the 99m Tc‐MAA scan to be used for dosimetry planning is being investigated within trials 13,14 . Our algorithm does not take such (intrahepatic) measures into account and hence should be modified if the above methods are introduced in regular clinical practice.…”