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Chauhan N, Bukovcan J, Boucher E, et al. 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. JMIR Res Protoc. 2018;7(8):e11234doi: 10.2196/11234.
Chauhan, N., Bukovcan, J., Boucher, E., Cosgrove, D., Edeline, J., Hamilton, B., Kulik, L., Master, F., & Salem, R. (2018). 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. JMIR research protocols, 7(8), e11234. https://doi.org/10.2196/11234
Chauhan, Nikhil, et al. "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." JMIR research protocols vol. 7,8 (2018): e11234. doi: https://doi.org/10.2196/11234
Chauhan N, Bukovcan J, Boucher E, Cosgrove D, Edeline J, Hamilton B, Kulik L, Master F, Salem R. 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. JMIR Res Protoc. 2018 Aug 15;7(8):e11234. doi: 10.2196/11234. PMID: 30111528; PMCID: PMC6115595.
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JMIR Res Protoc. 2018 Aug 15;7(8):e11234. doi: 10.2196/11234.

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.

JMIR research protocols

Nikhil Chauhan, Janet Bukovcan, Eveline Boucher, David Cosgrove, Julien Edeline, Bonnie Hamilton, Laura Kulik, Fayaz Master, Riad Salem

Affiliations

  1. Research and Development, BTG International Group Companies, London, United Kingdom.
  2. Division of Medical Oncology, Compass Oncology, Vancouver Cancer Center, Vancouver, WA, United States.
  3. Department of Oncology, Centre Eugene Marquis, Rennes, France.
  4. Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern Memorial Hospital, Chicago, IL, United States.
  5. Section of Interventional Radiology, Department of Radiology, Northwestern University, Chicago, IL, United States.
  6. Division of Hematology and Oncology, Department of Medicine, Northwestern University, Chicago, IL, United States.
  7. Division of Transplant Surgery, Department of Surgery, Northwestern University, Chicago, IL, United States.

PMID: 30111528 PMCID: PMC6115595 DOI: 10.2196/11234

Abstract

BACKGROUND: Globally, hepatocellular carcinoma is the second most common cause of cancer deaths. It remains challenging to intensify cancer treatment without impairing liver function.

OBJECTIVE: The 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.

METHODS: STOP-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).

RESULTS: Enrollment 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.

CONCLUSIONS: The 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 tumor thrombosis.

TRIAL REGISTRATION: ClinicalTrials.gov NCT01556490; https://clinicaltrials.gov/ct2/show/NCT01556490 (Archived by WebCite at http://www.webcitation.org/7188iygKs).

REGISTERED REPORT IDENTIFIER: RR1-10.2196/11234.

©Nikhil Chauhan, Janet Bukovcan, Eveline Boucher, David Cosgrove, Julien Edeline, Bonnie Hamilton, Laura Kulik, Fayaz Master, Riad Salem. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 15.08.2018.

Keywords: carcinoma, hepatocellular; clinical trial, phase III; hepatocellular carcinoma; microspheres; randomized controlled trial; research design; sorafenib; yttrium radioisotopes

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