NCT00105443 · CITED IN SOURCE DOCUMENTS

A Phase III Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2014-10-31

The purpose of the study is: Find out if patients receiving sorafenib will live longer. Find out if sorafenib has any effect on patient reported outcomes. Find out if sorafenib prevents the growth of or shrinks liver tumors and/or their metastases. Determine the pharmacokinetics (PK) in patients with liver cancer.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Overall Survival (OS)

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outcome · POSTED

Time to Symptomatic Progression (TTSP)

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outcome · POSTED

Time to Progression (TTP)

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outcome · POSTED

Disease Control (DC)

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outcome · POSTED

Patients Reported Outcome (PRO) by Use of the FACT-Hep Questionnaire

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outcome · POSTED

Overall Survival

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outcome · POSTED

Time to Symptomatic Progression (TTSP)

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outcome · POSTED

Time to Progression (TTP)

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outcome · POSTED

Disease Control (DC)

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outcome · POSTED

Patients Reported Outcome (PRO) by Use of the FACT-Hep Questionnaire

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * Ages eligible for study: 18 years and above, Genders eligible for study: both * Patients who have a life expectancy of at least 12 weeks * Patients with histologically or cytologically documented Hepatocellular Carcinoma (HCC) * Patients must have at least one tumor lesion that meets both of the following criteria: (1) Accurately measured in at least one dimension according to RECIST (Response Evaluation Criteria in Solid Tumors) (2) Not previously treated with local therapy * Patients who have an ECOG (Eastern Cooperative Oncology Group) PS (Performance Status) of 0, 1, or 2 Exclusion Criteria: * Previous or concurrent cancer that is distinct in primary site or histology from HCC, EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (Ta \[Noninvasive papillary carcinoma\], Tis \[Carcinoma in situ: "flat tumor"\] \& T1 \[Tumor invades subepithelial connective tissue\]). Any cancer curatively treated \> 3 years prior to entry is permitted * Renal failure requiring hemo- or peritoneal dialysis * History of cardiac disease * Active clinically serious infections * Known history of human immunodeficiency virus (HIV) infection * Known central nervous system tumors including metastatic brain disease * Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily; 2 dose reductions to predefined levels of 400 mg once daily (OD) and 400 mg every other day were permitted for adverse events related to study treatment. Follow-up / Open Label phase: Subjects on sorafenib who continued the study, continued on the same dose of sorafenib as during the double-blind study.
intervention Names
Drug: Sorafenib (Nexavar, BAY43-9006)
label
Sorafenib (Nexavar, BAY43-9006)
type
EXPERIMENTAL
description
Sorafenib-matching placebo tablets were orally administered twice daily (bid). Follow-up / Open Label phase: Subjects on placebo who chose to switch to sorafenib, received an oral dose of 400 mg (2 x 200 mg tablets) bid; similar to the double-blind study.
intervention Names
Drug: Placebo
label
Placebo
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Sorafenib (Nexavar, BAY43-9006)
description
Sorafenib 400 mg was administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid); 2 dose reductions to predefined levels of 400 mg once daily (OD) and 400 mg every other day were permitted for adverse events related to study treatment.
name
Sorafenib (Nexavar, BAY43-9006)
type
DRUG
arm Group Labels
Placebo
description
Sorafenib-matching placebo tablets were orally administered twice daily (bid).
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 602
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Overall Survival was defined as the time from date of starting treatment to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
measure
Overall Survival (OS)
time Frame
from randomization to death due to any cause until an average 7.2 months later up to the data cut-off date approximately 19 months after start of enrollment
description
TTSP was defined as the time from randomization to the first documented symptomatic progression.
measure
Time to Symptomatic Progression (TTSP)
time Frame
from randomization to the first documented symptomatic progression until an average 4.8 months later up to the data cut-off date approximately 19 months after start of enrollment

secondary Outcomes

description
TTP was defined as the time from randomization to disease progression (radiological only). Subjects without tumor progression at the time of analysis were censored at their last date of tumor evaluation.
measure
Time to Progression (TTP)
time Frame
from randomization to disease progression based on radiological assessment until an average 2.8 months later up to the data cut-off date approximately 19 months after start of enrollment
description
The DC is defined as the number of subjects with a best response rating of complete response (CR), partial response (PR), or stable disease (SD) that is maintained at least 28 days from the first manifestation of that rating. Definitions: CR = disappearance of all clinical and radiological tumor lesions; PR = at least 30% decrease in sum of the longest diameters of tumor lesions; SD = neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease.
measure
Disease Control (DC)
time Frame
time from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment
description
PRO is a disease-specific measure, developed as symptom-focused approach in HCC and measured by the response rates for the PWB and FWB subscales of the 45-item Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire. The FACT-Hep response rate was based on the number of subjects who achieved the 8-point minimally important difference (MID) for this subscale. FACT-Hep total score ranges from 0 to 180, where the highest score represents a maximum achievable quality of life (QoL) value.
measure
Patients Reported Outcome (PRO) by Use of the FACT-Hep Questionnaire
time Frame
from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment

Full study description

brief Summary: The purpose of the study is: Find out if patients receiving sorafenib will live longer. Find out if sorafenib has any effect on patient reported outcomes. Find out if sorafenib prevents the growth of or shrinks liver tumors and/or their metastases. Determine the pharmacokinetics (PK) in patients with liver cancer.
detailed Description: The following abbreviations were used in the Adverse Event section: * international normalized ratio (inr) * Common Terminology Criteria for Adverse Events (ctcae) * Not Otherwise Specified (nos) * Gastrointestinal (gi) * Central nervous system (cns) * Absolute Neutrophil Count (anc) * Alanine aminotransferase (ALT) * Aspartate aminotransferase (AST) * Creatine phosphokinase (cpk) * Gammaglutamyltransferase (ggt) * Genitourinary (gu) * Atrioventricular (av)

Source references

references

citation
Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Haussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008 Jul 24;359(4):378-90. doi: 10.1056/NEJMoa0708857.
pmid
18650514
type
RESULT
citation
Wu W, Mao H, Song J, Yang F. Bibliometric analysis of hepatocellular carcinoma and tyrosine kinase inhibitors. Medicine (Baltimore). 2025 May 16;104(20):e42015. doi: 10.1097/MD.0000000000042015.
pmid
40388796
type
DERIVED
citation
Bruix J, Cheng AL, Meinhardt G, Nakajima K, De Sanctis Y, Llovet J. Prognostic factors and predictors of sorafenib benefit in patients with hepatocellular carcinoma: Analysis of two phase III studies. J Hepatol. 2017 Nov;67(5):999-1008. doi: 10.1016/j.jhep.2017.06.026. Epub 2017 Jul 4.
pmid
28687477
type
DERIVED