Orantinib In Combination With Transcatheter Arterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma (ORIENTAL)

A Randomized, Double-Blind, Placebo-Controlled Phase III Trial Of TSU-68 In Combination With Transcatheter Arterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma

The purpose of this study is to compare the overall survival (OS) for Orantinib in combination with transcatheter arterial chemoembolization (TACE) versus placebo in combination with TACE in patients with unresectable hepatocellular carcinoma (HCC).

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Orantinib (TSU-68); Drug: Placebo

Detailed Description

This is a randomized, multi-center, double-blind, placebo-controlled phase III trial of Orantinib administered in combination with TACE in patients with unresectable HCC.

Patients will be randomly assigned (1:1) to receive TACE given in combination with either Orantinib (200 mg orally, twice per day) or placebo.

ORIENTAL:ORantinib InvEstigatioN on TAce combination triaL.

• Study Type: Interventional
• Enrollment (Actual): 888
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan, 260-8677
    • Local Institution
  • Osaka
    • Osaka-sayama, Osaka, Japan, 589-8511
      • Local Institution
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Local Institution
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Local Institution
  • Gyeonggi-do
    • Goyang-si, Gyeonggi-do, Korea, Republic of, 410-769
      • Local Institution
• Taiwan
  • Taipei, Taiwan, 100
    • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients must be diagnosed as HCC.
• Patients has no indications for treatment with curative hepatic resection or curative percutaneous local therapy.
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1.
• Patients are able to receive oral medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo; 1 tablet was administered orally twice per day after meals, morning and evening.
EXPERIMENTAL: Orantinib	Drug: Orantinib (TSU-68); 200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Survival(OS)	The time from the date of enrollment to the date of death from any cause, assessed up to three years after randomizationof the last patient

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Transcatheter Arterial Chemoembolization (TACE) Failure	Patients should not receive additional TACE therapy in this study after meeting any of the following conditions, at the Investigator's discretion.; The patient develops an intra-hepatic lesion that is uncontrolled by serial TACE; Deterioration in arterial pathways to treat HCC that makes additional TACE impossible; Severe vascular invasion occurs that makes additional TACE impossible; Extra hepatic spread considered relevant to life expectancy that requires another treatment modality for HCC; Liver function at grade Child-Pugh class C lasting for 28 days	The time from the date of enrollment to the date of event for TACE discontinuation, assessed up to three years after randomizationof the last patient

Collaborators and Investigators

• Sponsor: Taiho Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• Kudo M, Cheng AL, Park JW, Park JH, Liang PC, Hidaka H, Izumi N, Heo J, Lee YJ, Sheen IS, Chiu CF, Arioka H, Morita S, Arai Y. Orantinib versus placebo combined with transcatheter arterial chemoembolisation in patients with unresectable hepatocellular carcinoma (ORIENTAL): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet Gastroenterol Hepatol. 2018 Jan;3(1):37-46. doi: 10.1016/S2468-1253(17)30290-X. Epub 2017 Oct 4.

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (ACTUAL): June 1, 2014
• Study Completion (ACTUAL): November 1, 2014

Study Registration Dates

• First Submitted: November 1, 2011
• First Submitted That Met QC Criteria: November 3, 2011
• First Posted (ESTIMATE): November 4, 2011

Study Record Updates

• Last Update Posted (ACTUAL): August 7, 2019
• Last Update Submitted That Met QC Criteria: August 5, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Orantinib
• Other Study ID Numbers: Taiho132150