A Phase III Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma - Full Text View

Sponsor:	Bayer
Information provided by:	Bayer
ClinicalTrials.gov Identifier:	NCT00105443

Purpose

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.

Condition	Intervention	Phase
Carcinoma, Hepatocellular	Drug: Sorafenib (Nexavar, BAY43-9006) Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Phase III Randomized, Placebo-controlled Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Liver Cancer

Drug Information available for: Sorafenib Sorafenib tosylate

U.S. FDA Resources

Further study details as provided by Bayer:

Primary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
TTSP was defined as the time from randomization to the first documented symptomatic progression.

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.

Enrollment:	602
Study Start Date:	March 2005
Study Completion Date:	November 2008
Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sorafenib (Nexavar, BAY43-9006) 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.	Drug: Sorafenib (Nexavar, BAY43-9006) 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.
Placebo Comparator: Placebo 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.	Drug: Placebo Sorafenib-matching placebo tablets were orally administered twice daily (bid).

Arms

Assigned Interventions

Experimental: Sorafenib (Nexavar, BAY43-9006)

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.

Drug: Sorafenib (Nexavar, BAY43-9006)

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.

Placebo Comparator: Placebo

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.

Drug: Placebo

Sorafenib-matching placebo tablets were orally administered twice daily (bid).

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)

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00105443

Show 179 Study Locations

Sponsors and Collaborators

Bayer

Investigators

Study Director:

Bayer Study Director

Bayer

More Information

Additional Information:

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No publications provided by Bayer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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, Häussinger 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.

Responsible Party:	Therapeutic Area Head, Bayer HealthCare AG
ClinicalTrials.gov Identifier:	NCT00105443 History of Changes
Other Study ID Numbers:	100554, 2004-001773-26
Study First Received:	March 14, 2005
Results First Received:	December 11, 2009
Last Updated:	January 26, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Bayer:

Liver Cancer
Cancer

Additional relevant MeSH terms:

Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site

Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 12, 2012