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

Carcinoma, Hepatocellular Clinical Trial

— SHARP  

Official title:

A Phase III Randomized, Placebo-controlled Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00105443
• Other study ID #: 100554
• Secondary ID: 2004-001773-26
• Status: Completed
• Phase: Phase 3
• First received: March 14, 2005
• Last updated: October 24, 2014
• Start date: March 2005
• Est. completion date: November 2008

Study information

• Verified date: October 2014
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 602
• Est. completion date: November 2008
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  Croatia,  France,  Germany,  Greece,  Israel,  Italy,  Mexico,  New Zealand,  Peru,  Poland,  Romania,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

References & Publications (1)

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, B — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	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.	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	No
Primary	Time to Symptomatic Progression (TTSP)	TTSP was defined as the time from randomization to the first documented symptomatic progression.	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	No
Secondary	Time to Progression (TTP)	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.	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	No
Secondary	Disease Control (DC)	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.	time from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment	No
Secondary	Patients Reported Outcome (PRO) by Use of the FACT-Hep Questionnaire	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.	from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment	No

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