Official title: A Multinational, Randomized, Open-Label, Phase 3 Study Of Sunitinib Malate Versus Sorafenib In Patients With Advanced Hepatocellular Carcinoma

The study will evaluate the efficacy and safety of sunitinib (Arm A), given at 37.5 mg orally once daily, compared to sorafenib (Arm B), given orally at 400 mg twice daily, in patients with inoperable liver cancer. A total number of 1200 patients will be enrolled, 600 on Arm A and 600 on Arm B. Study treatment may be adjusted based on patient tolerance. and will be given until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. After discontinuation of study treatment, patients will be followed up in order to collect information on further antineoplastic therapy and survival.

Read the detailed description

This study was terminated on April 22th, 2010, based on a higher incidence of serious adverse events in the sunitinib arm compared to the sorafenib arm, and the fact that sunitinib did not meet the criteria to demonstrate that it was either superior or non-inferior to sorafenib in the survival of patients with advanced hepatocellular cancer. Patients on sunitinib who are judged by the investigator as receiving clinical benefit may chose to remain on study and continue treatment with sunitinib until clinical benefit as per the investigator's judgment.

Conditions: Carcinoma, Hepatocellular
Being tested: sunitinib malate, sorafenib
Keywords: sunitinib, phase 3, randomized, hepatocellular, liver
Medical subject headings: Carcinoma, Hepatocellular

What participants receive

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

sunitinib malateDrug
Also called Sutent®
sunitinib capsules at starting dose of 37.5 mg PO daily, until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. Sunitinib dosing interruptions and/or reductions are allowed based on patient tolerability.
sorafenibDrug
Also called Nexavar®
sorafenib tablets at starting dose of 400 mg PO twice daily, until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. Sorafenib dosing interruptions and/or reductions are allowed based on patient tolerability.

Study groups in NCT00699374
Study group	Role	What they receive
Arm A	Experimental	sunitinib arm Receives: Drug: sunitinib malate
Arm B	Active comparator	sorafenib arm Receives: Drug: sorafenib

What is being measured

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

Overall Survival (OS)
Overall survival is the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.
Measured: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150

Secondary outcomes (3)

Progression-Free Survival (PFS)
The period from randomization until disease progression or death.
Measured: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150
Time to Tumor Progression (TTP)
Time in weeks from randomization to first documentation of objective tumor progression or death due to cancer, whichever comes first. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD])
Measured: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150
European Quality of Life (EQ-5D)- Health State Profile Utility Score
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (eg, "confined to bed"). Scoring formula assigns a utility value for each domain in the profile. Score is transformed and results in a score range -0.594 to 1.000; higher score indicates better health state.
Measured: Day 1 of each cycle

Timeline

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

Jul 2008Dec 2011

First posted18 Jun 2008 (estimated)
Study startJul 2008
Primary completionDec 2011
Study completionDec 2011

Why it stopped: See termination reason in detailed description.

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 (3)Papers the sponsor has linked to this study.
Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
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: None (open label)
Enrolment: 1,075 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00699374
Sponsor's protocol ID: A6181170
Status last verified: Dec 2012
First submitted: 16 Jun 2008
Last updated: 14 Jan 2013
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Abuhelwa AY, Badaoui S, Yuen HY, McKinnon RA, Ruanglertboon W, Shankaran K, Tuteja A, Sorich MJ, Hopkins AM. A clinical scoring tool validated with machine learning for predicting severe hand-foot syndrome from sorafenib in hepatocellular carcinoma. Cancer Chemother Pharmacol. 2022 Apr;89(4):479-485. doi: 10.1007/s00280-022-04411-9. Epub 2022 Feb 28.
PubMed 35226112
Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, Chung HC, Song X, Xu J, Poggi G, Omata M, Pitman Lowenthal S, Lanzalone S, Yang L, Lechuga MJ, Raymond E. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol. 2013 Nov 10;31(32):4067-75. doi: 10.1200/JCO.2012.45.8372. Epub 2013 Sep 30.
PubMed 24081937
Koeberle D, Montemurro M, Samaras P, Majno P, Simcock M, Limacher A, Lerch S, Kovacs K, Inauen R, Hess V, Saletti P, Borner M, Roth A, Bodoky G. Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06). Oncologist. 2010;15(3):285-92. doi: 10.1634/theoncologist.2009-0316. Epub 2010 Mar 4.
PubMed 20203173

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

RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma

All Carcinoma, Hepatocellular trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multinational, Randomized, Open-Label, Phase 3 Study Of Sunitinib Malate Versus Sorafenib In Patients With Advanced Hepatocellular Carcinoma
ClinicalTrials.gov ID: NCT00699374
Acronym / sponsor ID: A6181170
Conditions: Carcinoma, Hepatocellular
Keywords: sunitinib, phase 3, randomized, hepatocellular, liver
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: See termination reason in detailed description.
Enrolment: 1,075 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: Jul 2008
Primary completion: Dec 2011 (actual)
Study completion: Dec 2011 (actual)
First posted: 18 Jun 2008 (estimated)
Results: Posted 14 Jan 2013

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Arm A	Experimental	Drug: sunitinib malatesunitinib arm
Arm B	Active comparator	Drug: sorafenibsorafenib arm

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Histologically-confirmed diagnosis of hepatocellular carcinoma
presence of measurable disease by radiographic imaging
Child-Pugh class A
ECOG PS 0 or 1
adequate organ function.

Key exclusion criteria (7 listed)

Prior treatment with any systemic treatment for hepatocellular carcinoma
prior local treatment within 4 weeks from entry
presence of clinically relevant ascites
severe hemorrhage <4 weeks of starting study treatment
known HIV or serious acute or chronic illness

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
sunitinib malateAlso: Sutent®sunitinib capsules at starting dose of 37.5 mg PO daily, until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. Sunitinib dosing interruptions and/or reductions are allowed based on patient tolerability.	Drug	Arm A
sorafenibAlso: Nexavar®sorafenib tablets at starting dose of 400 mg PO twice daily, until disease progression, occurrence of unacceptable toxicity, or other withdrawal criteria are met. Sorafenib dosing interruptions and/or reductions are allowed based on patient tolerability.	Drug	Arm B

Primary outcome

Overall Survival (OS)
Time frame: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150
Overall survival is the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact.

3 secondary outcomes

Progression-Free Survival (PFS)
Time frame: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150
Time to Tumor Progression (TTP)
Time frame: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150
European Quality of Life (EQ-5D)- Health State Profile Utility Score
Time frame: Day 1 of each cycle

Results and safety

Results posted to the registry on 14 Jan 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sunitinib	530	0
Sorafenib	544	0

Primary outcome: Overall Survival (OS)

Time frame: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150. Median (95% Confidence Interval). Unit: Weeks

Measure	Sunitinib n = 530	Sorafenib n = 544
Value	34.3 (31.9 to 39.9)	43.9 (38.1 to 48.7)

Sunitinib vs Sorafenib: Hazard Ratio (HR): 1.31 (95% CI 1.14 to 1.50), p = 0.9993, Log Rank

Population analysed: Full Analysis Population, all randomized participants where participants were classifed according to the randomized treatment arm regardless of what treatment, if any, was received.

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sunitinib	240 of 526 (45.6%)	515 of 526 (97.9%)	Not reported
Sorafenib	204 of 542 (37.6%)	531 of 542 (98%)	Not reported

Limitations and caveats (from the sponsor): Study terminated early due to futility. Subsequently, EQ-5D data were not collected or analyzed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2013.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35226112Abuhelwa AY, Badaoui S, Yuen HY, McKinnon RA, Ruanglertboon W, Shankaran K, Tuteja A, Sorich MJ, Hopkins AM. A clinical scoring tool validated with machine learning for predicting severe hand-foot syndrome from sorafenib in hepatocellular carcinoma. Cancer Chemother Pharmacol. 2022 Apr;89(4):479-485. doi: 10.1007/s00280-022-04411-9. Epub 2022 Feb 28.
Derived from this study: PubMed 24081937Cheng AL, Kang YK, Lin DY, Park JW, Kudo M, Qin S, Chung HC, Song X, Xu J, Poggi G, Omata M, Pitman Lowenthal S, Lanzalone S, Yang L, Lechuga MJ, Raymond E. Sunitinib versus sorafenib in advanced hepatocellular cancer: results of a randomized phase III trial. J Clin Oncol. 2013 Nov 10;31(32):4067-75. doi: 10.1200/JCO.2012.45.8372. Epub 2013 Sep 30.
Derived from this study: PubMed 20203173Koeberle D, Montemurro M, Samaras P, Majno P, Simcock M, Limacher A, Lerch S, Kovacs K, Inauen R, Hess V, Saletti P, Borner M, Roth A, Bodoky G. Continuous Sunitinib treatment in patients with advanced hepatocellular carcinoma: a Swiss Group for Clinical Cancer Research (SAKK) and Swiss Association for the Study of the Liver (SASL) multicenter phase II trial (SAKK 77/06). Oncologist. 2010;15(3):285-92. doi: 10.1634/theoncologist.2009-0316. Epub 2010 Mar 4.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.

Related trials for Carcinoma, Hepatocellular

RecruitingObservational study
Real-world Evaluation of the HistoSonics Edison System for Treatment of Liver Tumors Across Multidisciplinary Users (BOOMBOX: Master Study)
Liver Neoplasms, Primary Liver Cancer
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
Prospective Exploratory Study of FAPi PET/CT With Histopathology Validation in Patients With Various Cancers
Bladder Carcinoma, Cervical Carcinoma
RecruitingObservational study
A Study to Evaluate Patient-Reported Satisfaction, Effectiveness, and Safety of Atezolizumab in Participants Treated in Routine Clinical Practice
Lung Cancer, Hepatocellular Carcinoma
RecruitingPhase 2
At-Home Cancer Directed Therapy Versus in Clinic for the Treatment of Patients With Advanced Cancer
Advanced Anal Carcinoma, Advanced Biliary Tract Carcinoma

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.

Pfizer CT.gov Call Center study director

Pfizer

171 sites in 23 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing sunitinib malate and sorafenib in people with Carcinoma, Hepatocellular, run by Pfizer at 171 sites in 23 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 5 inclusion and 7 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 14 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 171 sites in United States, Japan, China, France, South Korea and 18 more countries. 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. 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 14 Jan 2013). 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: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150). 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 NCT00699374, which also lists 3 linked publications.

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 14 Jan 2013; AzTrials last refreshed its copy on 7 Nov 2026.