Therasphere yttrium-90 glass microspheres combined with chemotherapy versus chemotherapy alone in second-line treatment of patients with metastatic colorectal carcinoma of the liver

Protocol for the EPOCH phase 3 randomized clinical trial

Nikhil Chauhan, Mary Frances Mulcahy, Riad Salem, Al B Benson III, Eveline Boucher, Janet Bukovcan, David Cosgrove, Chantal Laframboise, Robert J Lewandowski, Fayaz Master, Bassel El-Rayes, Jonathan R. Strosberg, Daniel Y. Sze, Ricky A. Sharma

Research output: Contribution to journalArticle

Abstract

Background: Colorectal cancer is one of the most common cancers and causes of cancer-related death. Up to approximately 70% of patients with metastatic colorectal cancer (mCRC) have metastases to the liver at initial diagnosis. Second-line systemic treatment in mCRC can prolong survival after development of disease progression during or after first-line treatment and in those who are intolerant to first-line treatment. Objective: The objective of this study is to evaluate the efficacy and safety of transarterial radioembolization (TARE) with TheraSphere yttrium-90 ( 90 Y) glass microspheres combined with second-line therapy in patients with mCRC of the liver who had disease progression during or after first-line chemotherapy. Methods: EPOCH is an open-label, prospective, multicenter, randomized, phase 3 trial being conducted at up to 100 sites in the United States, Canada, Europe, and Asia. Eligible patients have mCRC of the liver and disease progression after first-line chemotherapy with either an oxaliplatin-based or irinotecan-based regimen and are eligible for second-line chemotherapy with the alternate regimen. Patients were randomized 1:1 to the TARE group (chemotherapy with TARE in place of the second chemotherapy infusion and subsequent resumption of chemotherapy) or the control group (chemotherapy alone). The addition of targeted agents is permitted. The primary end points are progression-free survival and hepatic progression-free survival. The study objective will be considered achieved if at least one primary end point is statistically significant. Secondary end points are overall survival, time to symptomatic progression defined as Eastern Cooperative Oncology Group Performance Status score of 2 or higher, objective response rate, disease control rate, quality-of-life assessment by the Functional Assessment of Cancer Therapy-Colorectal Cancer questionnaire, and adverse events. The study is an adaptive trial, comprising a group sequential design with 2 interim analyses with a planned maximum of 420 patients. The study is designed to detect a 2.5-month increase in median progression-free survival, from 6 months in the control group to 8.5 months in the TARE group (hazard ratio [HR] 0.71), and a 3.5-month increase in median hepatic progression-free survival time, from 6.5 months in the control group to 10 months in the TARE group (HR 0.65). On the basis of simulations, the power to detect the target difference in either progression-free survival or hepatic progression-free survival is >90%, and the power to detect the target difference in each end point alone is >80%. Results: Patient enrollment ended in October 2018. The first interim analysis in June 2018 resulted in continuation of the study without any changes. Conclusions: The EPOCH study may contribute toward the establishment of the role of combination therapy with TARE and oxaliplatin- or irinotecan-based chemotherapy in the second-line treatment of mCRC of the liver.

Original languageEnglish (US)
Article numbere11545
JournalJournal of medical Internet research
Volume21
Issue number1
DOIs
StatePublished - Jan 1 2019

Fingerprint

Yttrium
Phase III Clinical Trials
Microspheres
Glass
Colorectal Neoplasms
Randomized Controlled Trials
Disease-Free Survival
Drug Therapy
oxaliplatin
irinotecan
Liver
Liver Neoplasms
Disease Progression
Therapeutics
Control Groups
Neoplasms
Survival
EPOCH protocol
Canada
Liver Diseases

Keywords

  • Clinical trial, phase III
  • Colorectal neoplasms
  • MCRC
  • Metastatic colorectal cancer
  • Microspheres
  • Neoplasm metastasis
  • Randomized controlled trial
  • Research design
  • Yttrium radioisotopes

ASJC Scopus subject areas

  • Health Informatics

Cite this

@article{d588793c2827470a92eb543863c625b0,
title = "Therasphere yttrium-90 glass microspheres combined with chemotherapy versus chemotherapy alone in second-line treatment of patients with metastatic colorectal carcinoma of the liver: Protocol for the EPOCH phase 3 randomized clinical trial",
abstract = "Background: Colorectal cancer is one of the most common cancers and causes of cancer-related death. Up to approximately 70{\%} of patients with metastatic colorectal cancer (mCRC) have metastases to the liver at initial diagnosis. Second-line systemic treatment in mCRC can prolong survival after development of disease progression during or after first-line treatment and in those who are intolerant to first-line treatment. Objective: The objective of this study is to evaluate the efficacy and safety of transarterial radioembolization (TARE) with TheraSphere yttrium-90 ( 90 Y) glass microspheres combined with second-line therapy in patients with mCRC of the liver who had disease progression during or after first-line chemotherapy. Methods: EPOCH is an open-label, prospective, multicenter, randomized, phase 3 trial being conducted at up to 100 sites in the United States, Canada, Europe, and Asia. Eligible patients have mCRC of the liver and disease progression after first-line chemotherapy with either an oxaliplatin-based or irinotecan-based regimen and are eligible for second-line chemotherapy with the alternate regimen. Patients were randomized 1:1 to the TARE group (chemotherapy with TARE in place of the second chemotherapy infusion and subsequent resumption of chemotherapy) or the control group (chemotherapy alone). The addition of targeted agents is permitted. The primary end points are progression-free survival and hepatic progression-free survival. The study objective will be considered achieved if at least one primary end point is statistically significant. Secondary end points are overall survival, time to symptomatic progression defined as Eastern Cooperative Oncology Group Performance Status score of 2 or higher, objective response rate, disease control rate, quality-of-life assessment by the Functional Assessment of Cancer Therapy-Colorectal Cancer questionnaire, and adverse events. The study is an adaptive trial, comprising a group sequential design with 2 interim analyses with a planned maximum of 420 patients. The study is designed to detect a 2.5-month increase in median progression-free survival, from 6 months in the control group to 8.5 months in the TARE group (hazard ratio [HR] 0.71), and a 3.5-month increase in median hepatic progression-free survival time, from 6.5 months in the control group to 10 months in the TARE group (HR 0.65). On the basis of simulations, the power to detect the target difference in either progression-free survival or hepatic progression-free survival is >90{\%}, and the power to detect the target difference in each end point alone is >80{\%}. Results: Patient enrollment ended in October 2018. The first interim analysis in June 2018 resulted in continuation of the study without any changes. Conclusions: The EPOCH study may contribute toward the establishment of the role of combination therapy with TARE and oxaliplatin- or irinotecan-based chemotherapy in the second-line treatment of mCRC of the liver.",
keywords = "Clinical trial, phase III, Colorectal neoplasms, MCRC, Metastatic colorectal cancer, Microspheres, Neoplasm metastasis, Randomized controlled trial, Research design, Yttrium radioisotopes",
author = "Nikhil Chauhan and Mulcahy, {Mary Frances} and Riad Salem and {Benson III}, {Al B} and Eveline Boucher and Janet Bukovcan and David Cosgrove and Chantal Laframboise and Lewandowski, {Robert J} and Fayaz Master and Bassel El-Rayes and Strosberg, {Jonathan R.} and Sze, {Daniel Y.} and Sharma, {Ricky A.}",
year = "2019",
month = "1",
day = "1",
doi = "10.2196/11545",
language = "English (US)",
volume = "21",
journal = "Journal of Medical Internet Research",
issn = "1439-4456",
publisher = "Journal of medical Internet Research",
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}

Therasphere yttrium-90 glass microspheres combined with chemotherapy versus chemotherapy alone in second-line treatment of patients with metastatic colorectal carcinoma of the liver : Protocol for the EPOCH phase 3 randomized clinical trial. / Chauhan, Nikhil; Mulcahy, Mary Frances; Salem, Riad; Benson III, Al B; Boucher, Eveline; Bukovcan, Janet; Cosgrove, David; Laframboise, Chantal; Lewandowski, Robert J; Master, Fayaz; El-Rayes, Bassel; Strosberg, Jonathan R.; Sze, Daniel Y.; Sharma, Ricky A.

In: Journal of medical Internet research, Vol. 21, No. 1, e11545, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Therasphere yttrium-90 glass microspheres combined with chemotherapy versus chemotherapy alone in second-line treatment of patients with metastatic colorectal carcinoma of the liver

T2 - Protocol for the EPOCH phase 3 randomized clinical trial

AU - Chauhan, Nikhil

AU - Mulcahy, Mary Frances

AU - Salem, Riad

AU - Benson III, Al B

AU - Boucher, Eveline

AU - Bukovcan, Janet

AU - Cosgrove, David

AU - Laframboise, Chantal

AU - Lewandowski, Robert J

AU - Master, Fayaz

AU - El-Rayes, Bassel

AU - Strosberg, Jonathan R.

AU - Sze, Daniel Y.

AU - Sharma, Ricky A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Colorectal cancer is one of the most common cancers and causes of cancer-related death. Up to approximately 70% of patients with metastatic colorectal cancer (mCRC) have metastases to the liver at initial diagnosis. Second-line systemic treatment in mCRC can prolong survival after development of disease progression during or after first-line treatment and in those who are intolerant to first-line treatment. Objective: The objective of this study is to evaluate the efficacy and safety of transarterial radioembolization (TARE) with TheraSphere yttrium-90 ( 90 Y) glass microspheres combined with second-line therapy in patients with mCRC of the liver who had disease progression during or after first-line chemotherapy. Methods: EPOCH is an open-label, prospective, multicenter, randomized, phase 3 trial being conducted at up to 100 sites in the United States, Canada, Europe, and Asia. Eligible patients have mCRC of the liver and disease progression after first-line chemotherapy with either an oxaliplatin-based or irinotecan-based regimen and are eligible for second-line chemotherapy with the alternate regimen. Patients were randomized 1:1 to the TARE group (chemotherapy with TARE in place of the second chemotherapy infusion and subsequent resumption of chemotherapy) or the control group (chemotherapy alone). The addition of targeted agents is permitted. The primary end points are progression-free survival and hepatic progression-free survival. The study objective will be considered achieved if at least one primary end point is statistically significant. Secondary end points are overall survival, time to symptomatic progression defined as Eastern Cooperative Oncology Group Performance Status score of 2 or higher, objective response rate, disease control rate, quality-of-life assessment by the Functional Assessment of Cancer Therapy-Colorectal Cancer questionnaire, and adverse events. The study is an adaptive trial, comprising a group sequential design with 2 interim analyses with a planned maximum of 420 patients. The study is designed to detect a 2.5-month increase in median progression-free survival, from 6 months in the control group to 8.5 months in the TARE group (hazard ratio [HR] 0.71), and a 3.5-month increase in median hepatic progression-free survival time, from 6.5 months in the control group to 10 months in the TARE group (HR 0.65). On the basis of simulations, the power to detect the target difference in either progression-free survival or hepatic progression-free survival is >90%, and the power to detect the target difference in each end point alone is >80%. Results: Patient enrollment ended in October 2018. The first interim analysis in June 2018 resulted in continuation of the study without any changes. Conclusions: The EPOCH study may contribute toward the establishment of the role of combination therapy with TARE and oxaliplatin- or irinotecan-based chemotherapy in the second-line treatment of mCRC of the liver.

AB - Background: Colorectal cancer is one of the most common cancers and causes of cancer-related death. Up to approximately 70% of patients with metastatic colorectal cancer (mCRC) have metastases to the liver at initial diagnosis. Second-line systemic treatment in mCRC can prolong survival after development of disease progression during or after first-line treatment and in those who are intolerant to first-line treatment. Objective: The objective of this study is to evaluate the efficacy and safety of transarterial radioembolization (TARE) with TheraSphere yttrium-90 ( 90 Y) glass microspheres combined with second-line therapy in patients with mCRC of the liver who had disease progression during or after first-line chemotherapy. Methods: EPOCH is an open-label, prospective, multicenter, randomized, phase 3 trial being conducted at up to 100 sites in the United States, Canada, Europe, and Asia. Eligible patients have mCRC of the liver and disease progression after first-line chemotherapy with either an oxaliplatin-based or irinotecan-based regimen and are eligible for second-line chemotherapy with the alternate regimen. Patients were randomized 1:1 to the TARE group (chemotherapy with TARE in place of the second chemotherapy infusion and subsequent resumption of chemotherapy) or the control group (chemotherapy alone). The addition of targeted agents is permitted. The primary end points are progression-free survival and hepatic progression-free survival. The study objective will be considered achieved if at least one primary end point is statistically significant. Secondary end points are overall survival, time to symptomatic progression defined as Eastern Cooperative Oncology Group Performance Status score of 2 or higher, objective response rate, disease control rate, quality-of-life assessment by the Functional Assessment of Cancer Therapy-Colorectal Cancer questionnaire, and adverse events. The study is an adaptive trial, comprising a group sequential design with 2 interim analyses with a planned maximum of 420 patients. The study is designed to detect a 2.5-month increase in median progression-free survival, from 6 months in the control group to 8.5 months in the TARE group (hazard ratio [HR] 0.71), and a 3.5-month increase in median hepatic progression-free survival time, from 6.5 months in the control group to 10 months in the TARE group (HR 0.65). On the basis of simulations, the power to detect the target difference in either progression-free survival or hepatic progression-free survival is >90%, and the power to detect the target difference in each end point alone is >80%. Results: Patient enrollment ended in October 2018. The first interim analysis in June 2018 resulted in continuation of the study without any changes. Conclusions: The EPOCH study may contribute toward the establishment of the role of combination therapy with TARE and oxaliplatin- or irinotecan-based chemotherapy in the second-line treatment of mCRC of the liver.

KW - Clinical trial, phase III

KW - Colorectal neoplasms

KW - MCRC

KW - Metastatic colorectal cancer

KW - Microspheres

KW - Neoplasm metastasis

KW - Randomized controlled trial

KW - Research design

KW - Yttrium radioisotopes

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JO - Journal of Medical Internet Research

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