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

TheraSphere STOP-HCC Protocol Study Group

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish (US)
Article numbere11234
JournalJournal of medical Internet research
Volume20
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Yttrium
Microspheres
Glass
Hepatocellular Carcinoma
Randomized Controlled Trials
Therapeutics
Sample Size
Neoplasms
Portal Vein
Survival
sorafenib
Thrombosis
Clinical Trials Data Monitoring Committees
Northern Asia
Clinical Protocols
North America
Life Expectancy
Multicenter Studies
Cause of Death

Keywords

  • Carcinoma
  • Clinical trial
  • Hepatocellular
  • Hepatocellular carcinoma
  • Microspheres
  • Phase III
  • Randomized controlled trial
  • Research design
  • Sorafenib
  • Yttrium radioisotopes

ASJC Scopus subject areas

  • Health Informatics

Cite this

@article{1a6e9411c9784da3924ccff28fec6bfa,
title = "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 = "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.",
keywords = "Carcinoma, Clinical trial, Hepatocellular, Hepatocellular carcinoma, Microspheres, Phase III, Randomized controlled trial, Research design, Sorafenib, Yttrium radioisotopes",
author = "{TheraSphere STOP-HCC Protocol Study Group} and Nikhil Chauhan and Janet Bukovcan and Eveline Boucher and David Cosgrove and Julien Edeline and Bonnie Hamilton and Kulik, {Laura M} and Fayaz Master and Riad Salem and {Kevin Kim}, H. and Bassel El-Rayes and Jorg Schlaak and Stephen Cohen and Raoul, {Jean Luc} and Jonathan Strosberg and Bulent Arslan and Ravi Shridhar and Matt Johnson and Mary Maluccio and Dan Brown and Jeff Geschwind and David Cosgrove and Michael Choti and Andrew Zhu and Lewis Roberts and Bill Rilling and Ravi Murthy and Ahmed Kaseb and Vincenzo Mazzaferro and Laura Kulik and Mulcahy, {Mary Frances} and Riad Salem and Bob Lewandowski and {Benson III}, {Al B} and Mark Bloomston and Tony Saab and Hooman Khabiri and Daniel Sze and Wells Messersmith and Jan Durham and Nicholas Fidelman and Zhao, {Hua Ching}",
year = "2018",
month = "8",
day = "1",
doi = "10.2196/11234",
language = "English (US)",
volume = "20",
journal = "Journal of Medical Internet Research",
issn = "1439-4456",
publisher = "Journal of medical Internet Research",
number = "8",

}

TY - JOUR

T1 - Intra-arterial TheraSphere yttrium-90 glass microspheres in the treatment of patients with unresectable hepatocellular carcinoma

T2 - Protocol for the STOP-HCC phase 3 randomized controlled trial

AU - TheraSphere STOP-HCC Protocol Study Group

AU - Chauhan, Nikhil

AU - Bukovcan, Janet

AU - Boucher, Eveline

AU - Cosgrove, David

AU - Edeline, Julien

AU - Hamilton, Bonnie

AU - Kulik, Laura M

AU - Master, Fayaz

AU - Salem, Riad

AU - Kevin Kim, H.

AU - El-Rayes, Bassel

AU - Schlaak, Jorg

AU - Cohen, Stephen

AU - Raoul, Jean Luc

AU - Strosberg, Jonathan

AU - Arslan, Bulent

AU - Shridhar, Ravi

AU - Johnson, Matt

AU - Maluccio, Mary

AU - Brown, Dan

AU - Geschwind, Jeff

AU - Cosgrove, David

AU - Choti, Michael

AU - Zhu, Andrew

AU - Roberts, Lewis

AU - Rilling, Bill

AU - Murthy, Ravi

AU - Kaseb, Ahmed

AU - Mazzaferro, Vincenzo

AU - Kulik, Laura

AU - Mulcahy, Mary Frances

AU - Salem, Riad

AU - Lewandowski, Bob

AU - Benson III, Al B

AU - Bloomston, Mark

AU - Saab, Tony

AU - Khabiri, Hooman

AU - Sze, Daniel

AU - Messersmith, Wells

AU - Durham, Jan

AU - Fidelman, Nicholas

AU - Zhao, Hua Ching

PY - 2018/8/1

Y1 - 2018/8/1

N2 - 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.

AB - 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.

KW - Carcinoma

KW - Clinical trial

KW - Hepatocellular

KW - Hepatocellular carcinoma

KW - Microspheres

KW - Phase III

KW - Randomized controlled trial

KW - Research design

KW - Sorafenib

KW - Yttrium radioisotopes

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U2 - 10.2196/11234

DO - 10.2196/11234

M3 - Article

VL - 20

JO - Journal of Medical Internet Research

JF - Journal of Medical Internet Research

SN - 1439-4456

IS - 8

M1 - e11234

ER -