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Study Of Sunitinib Malate Versus Sorafenib In Patients With Inoperable Liver Cancer

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

Status
Terminated
Phases
Phase 3
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT00699374
Enrollment
1075
Registered
2008-06-18
Start date
2008-07-31
Completion date
2011-12-31
Last updated
2013-01-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Carcinoma, Hepatocellular

Keywords

sunitinib, phase 3, randomized, hepatocellular, liver

Brief summary

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.

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.

Interventions

DRUGsunitinib malate

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.

DRUGsorafenib

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.

Sponsors

Pfizer
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* 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.

Exclusion criteria

* 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 * current treatment on another clinical trial * pregnancy or breastfeeding

Design outcomes

Primary

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

Secondary

MeasureTime frameDescription
Progression-Free Survival (PFS)Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150The period from randomization until disease progression or death.
Time to Tumor Progression (TTP)Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150Time 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 \[PD\])
European Quality of Life (EQ-5D)- Health State Profile Utility ScoreDay 1 of each cycleEQ-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.

Countries

Australia, Belgium, Canada, China, France, Germany, Hong Kong, Italy, Japan, Malaysia, Philippines, Poland, Russia, Singapore, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States

Participant flow

Pre-assignment details

One participant was randomized twice, once to the sorafenib arm and discontinued prior to receiving treatment and a second randomization to the sunitinib arm and dispensed treatment.

Participants by arm

ArmCount
Sunitinib
Participants received sunitinib 37.5 milligram (mg) capsules by mouth once daily on a continuous daily dosing schedule. Dose reductions to either 25 mg or 12.5 mg were allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.
530
Sorafenib
Participants received sorafenib 400 mg tablets by mouth, twice daily (BID). Dose reduction to 400 mg once daily (QD) was allowed. Treatment continued until disease progression, death, unacceptable toxicity, withdrawal of participant consent, need for different cancer treatment, or another withdrawal criterion was met.
544
Total1,074

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyAdverse Event7067
Overall StudyDeath9383
Overall StudyDied 28 days after last dose59
Overall StudyGlobal deterioration of health status78
Overall StudyLost to Follow-up35
Overall StudyObjective progression or relapse281277
Overall StudyOther1815
Overall StudyProtocol Violation26
Overall StudyRandomized but not treated42
Overall StudyStudy terminated by sponsor1328
Overall StudyWithdrawal by Subject3444

Baseline characteristics

CharacteristicSunitinibSorafenibTotal
Age Continuous58.1 Years
STANDARD_DEVIATION 12.86
58.5 Years
STANDARD_DEVIATION 12.93
58.3 Years
STANDARD_DEVIATION 12.89
Sex: Female, Male
Female
94 Participants85 Participants179 Participants
Sex: Female, Male
Male
436 Participants459 Participants895 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
515 / 526531 / 542
serious
Total, serious adverse events
240 / 526204 / 542

Outcome results

Primary

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.

Time frame: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150

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

ArmMeasureValue (MEDIAN)
SunitinibOverall Survival (OS)34.3 Weeks
SorafenibOverall Survival (OS)43.9 Weeks
p-value: 0.999395% CI: [1.14, 1.5]Log Rank
Secondary

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.

Time frame: Day 1 of each cycle

Population: Data were not collected per Amendment 2 to the protocol removing collection for this endpoint.

Secondary

Progression-Free Survival (PFS)

The period from randomization until disease progression or death.

Time frame: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150

Population: Full Analysis Population

ArmMeasureValue (MEDIAN)
SunitinibProgression-Free Survival (PFS)15.3 Weeks
SorafenibProgression-Free Survival (PFS)12.6 Weeks
p-value: 0.885795% CI: [0.99, 1.3]Log Rank
Secondary

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 \[PD\])

Time frame: Baseline, every 4 weeks during treatment, every 8 weeks posttreatment up to Week 150

Population: Full Analysis Population

ArmMeasureValue (MEDIAN)
SunitinibTime to Tumor Progression (TTP)17.7 Weeks
SorafenibTime to Tumor Progression (TTP)15.4 Weeks
p-value: 0.845995% CI: [0.98, 1.31]Log Rank

Source: ClinicalTrials.gov · Data processed: Apr 1, 2026