Hepatocellular CarcinomaPhase 3ORIENTALNCT01465464

Orantinib In Combination With Transcatheter Arterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma

A Phase 3 study testing Orantinib (TSU-68) in people with Hepatocellular Carcinoma, run by Taiho Pharmaceutical Co., Ltd. at 6 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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). Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Hepatocellular Carcinoma
What is being tested?: Orantinib (TSU-68)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 888 participants
Where: 6 sitesin 3 countries
Study dates: Dec 2010to Nov 2014
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

None listed.

Trial locations and contacts

6 sites in 3 countries.

Country

City, postcode or hospital

6 sites in 3 countries

Japan3 sites

Local Institution
Chiba, 260-8677
Local Institution
Chuo-ku, Tokyo, 104-0045
Local Institution
Ōsaka-sayama, Osaka, 589-8511

Other trials in Japan

South Korea2 sites

Local Institution
Goyang-si, Gyeonggi-do, 410-769
Local Institution
Seoul, 110-744

Other trials in South Korea

Taiwan1 site

Local Institution
Taipei, 100

Other trials in Taiwan

About this study

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

Read the 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.

Conditions: Hepatocellular Carcinoma
Being tested: Orantinib (TSU-68), Placebo
Medical subject headings: Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Orantinib (TSU-68)Drug
200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening.
PlaceboDrug
1 tablet was administered orally twice per day after meals, morning and evening.

Study groups in NCT01465464
Study group	Role	What they receive
Orantinib	Experimental	Not described Receives: Drug: Orantinib (TSU-68)
Placebo	Placebo comparator	Not described Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Overall Survival(OS)
Measured: 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 outcomes (1)

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.
1. The patient develops an intra-hepatic lesion that is uncontrolled by serial TACE
2. Deterioration in arterial pathways to treat HCC that makes additional TACE impossible
3. Severe vascular invasion occurs that makes additional TACE impossible
4. Extra hepatic spread considered relevant to life expectancy that requires another treatment modality for HCC
5. Liver function at grade Child-Pugh class C lasting for 28 days
Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2010Nov 2014

First posted4 Nov 2011 (estimated)
Study startDec 2010
Primary completionJun 2014
Study completionNov 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 888 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01465464
Sponsor's protocol ID: Taiho132150
Acronym: ORIENTAL
Status last verified: Aug 2019
First submitted: 1 Nov 2011
Last updated: 7 Aug 2019
Results posted: Yes, on ClinicalTrials.gov

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.
PubMed 28988687

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Hepatocellular Carcinoma trials

Study at a glance

From the registry record, last updated by the sponsor on 7 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind, Placebo-Controlled Phase III Trial Of TSU-68 In Combination With Transcatheter Arterial Chemoembolization In Patients With Unresectable Hepatocellular Carcinoma
ClinicalTrials.gov ID: NCT01465464
Acronym / sponsor ID: ORIENTAL / Taiho132150
Conditions: Hepatocellular Carcinoma
Phase: Phase 3
Study type: Interventional
Recruitment status: Terminated
Enrolment: 888 participants (actual)
Lead sponsor: Taiho Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
Study start: Dec 2010
Primary completion: Jun 2014 (actual)
Study completion: Nov 2014 (actual)
First posted: 4 Nov 2011 (estimated)
Results: Posted 7 Aug 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Orantinib	Experimental	Drug: Orantinib (TSU-68)
Placebo	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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.

Key exclusion criteria (0 listed)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Orantinib (TSU-68)200 mg (1 tablet) of Orantinib was administered orally twice per day after meals, morning and evening.	Drug	Orantinib
Placebo1 tablet was administered orally twice per day after meals, morning and evening.	Drug	Placebo

Primary outcome

Overall Survival(OS)
Time frame: 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

1 secondary outcome

Time to Transcatheter Arterial Chemoembolization (TACE) Failure
Time frame: 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

Results and safety

Results posted to the registry on 7 Aug 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Orantinib	444	0
Placebo	444	0

Primary outcome: Overall Survival(OS)

Time frame: 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. Median (95% Confidence Interval). Unit: days

Measure	Orantinib n = 168	Placebo n = 163
Value	946.0 (807.0 to 1050.0)	984.0 (864.0 to NA)

Placebo: Hazard Ratio (HR): 1.090 (95% CI 0.878 to 1.352), p = 0.435, Log Rank

Population analysed: When approximately 50% of the targeted number of time to TACE discontinuation events were confirmed, interim analysis was performed by IDMC. Because the Committee considered that significant results would no longer be obtained, the IDMC recommended to the Sponsor that the clinical trial would be discontinued, and the Sponsor stopped this trial.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From the date of the first treatment to 30 days after the last treatment. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Orantinib	200 of 444 (45%)	443 of 444 (99.8%)	33 of 444
Placebo	134 of 444 (30.2%)	436 of 444 (98.2%)	24 of 444

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28988687Kudo 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.

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RecruitingObservational study
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Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Taiho Pharmaceutical Co., Ltd. study director

Taiho Pharmaceutical Co., Ltd.

6 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Orantinib (TSU-68) in people with Hepatocellular Carcinoma, run by Taiho Pharmaceutical Co., Ltd. at 6 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Japan, South Korea, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival(OS) (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01465464, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2019.