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

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ClinicalTrials.gov Identifier: NCT00105443
Recruitment Status : Completed
First Posted : March 15, 2005
Results First Posted : September 27, 2010
Last Update Posted : October 31, 2014
Sponsor:
Information provided by (Responsible Party):
Bayer

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.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Drug: Sorafenib (Nexavar, BAY43-9006) Drug: Placebo Phase 3

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)

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 602 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase III Randomized, Placebo-controlled Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Study Start Date : March 2005
Actual Primary Completion Date : November 2008
Actual Study Completion Date : November 2008

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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).




Primary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    TTSP was defined as the time from randomization to the first documented symptomatic progression.


Secondary Outcome Measures :
  1. 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 ]
    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.

  2. 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 ]
    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.

  3. 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 ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00105443


  Hide Study Locations
Locations
United States, Arizona
Phoenix, Arizona, United States, 85054-4502
Tucson, Arizona, United States, 85724
United States, California
Los Angeles, California, United States, 90057
Los Angeles, California, United States, 90095-7077
Orange, California, United States, 92668-3298
San Francisco, California, United States, 94121
Stanford, California, United States, 94305
United States, Connecticut
Farmington, Connecticut, United States, 06030
New Haven, Connecticut, United States, 06510-8019
United States, Florida
Gainesville, Florida, United States, 32610
Miami, Florida, United States, 33136
Tampa, Florida, United States, 33612
United States, Georgia
Atlanta, Georgia, United States, 30308
Atlanta, Georgia, United States, 30322
United States, Illinois
Chicago, Illinois, United States, 60611
Chicago, Illinois, United States, 60612
United States, Kentucky
Lexington, Kentucky, United States, 40536
United States, Michigan
Ann Arbor, Michigan, United States, 48109-0362
Detroit, Michigan, United States, 48202-2689
United States, Missouri
St. Louis, Missouri, United States, 63104
United States, Nebraska
Omaha, Nebraska, United States, 68198-2000
United States, New York
Manhasset, New York, United States, 11030-3876
New York, New York, United States, 10016
New York, New York, United States, 10021
New York, New York, United States, 10029
New York, New York, United States, 10032
United States, Ohio
Canton, Ohio, United States, 44718
United States, Oregon
Portland, Oregon, United States, 97239
United States, Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Philadelphia, Pennsylvania, United States, 19140
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Houston, Texas, United States, 77030-1502
United States, Virginia
Richmond, Virginia, United States, 23249
United States, Washington
Seattle, Washington, United States, 98104
Seattle, Washington, United States, 98195-6174
Argentina
Mar del Plata, Buenos Aires, Argentina, 7600
Pilar, Buenos Aires, Argentina, B1629AHJ
Bueno Aires, Ciudad Auton. de Buenos Aires, Argentina, C1417DTB
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1120AAF
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1145ADP
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1181ACH
San Miguel de Tucumán, Tucuman, Argentina, T4000GTB
San Miguel de Tucumán, Tucuman, Argentina, T4000HXU
Australia, New South Wales
Camperdown, New South Wales, Australia, 2050
Randwick, New South Wales, Australia, 2031
Westmead, New South Wales, Australia, 2145
Australia, Victoria
East Bentleigh, Victoria, Australia, 3165
Heidelberg, Victoria, Australia, 3084
Melbourne, Victoria, Australia, 3052
Belgium
Brugge, Belgium, 8000
Bruxelles - Brussel, Belgium, 1070
Bruxelles - Brussel, Belgium, 1090
Bruxelles - Brussel, Belgium, 1200
Gent, Belgium, 9000
Leuven, Belgium, 3000
Brazil
Porto Alegre, Rio Grande do Sul, Brazil, 90035-003
Porto Alegre, Rio Grande do Sul, Brazil, 90619900
Belo Horizonte, Brazil, 30180090
Belo Horizonte, Brazil, 30380490
Sao Paulo, Brazil, 01246-903
Bulgaria
Sofia, Bulgaria, 1233
Sofia, Bulgaria, 1431
Sofia, Bulgaria, 1527
Stara Zagora, Bulgaria, 6000
Varna, Bulgaria, 9010
Canada, Alberta
Calgary, Alberta, Canada, T2N 4N1
Edmonton, Alberta, Canada, T6G 2C8
Canada, British Columbia
Vancouver, British Columbia, Canada, V5Z 1H8
Canada, Manitoba
Winnipeg, Manitoba, Canada, R2H 2A6
Canada, Ontario
London, Ontario, Canada, N6A 5A5
Ottawa, Ontario, Canada, K1H 1C4
Toronto, Ontario, Canada, M5G 2N2
Canada, Quebec
Montreal, Quebec, Canada, H3A 1A1
Chile
Santiago de Chile, Santiago, Chile, 833-0024
Santiago de Chile, Chile
Santiago Región Metropolitana, Chile
Croatia
Zagreb, Croatia, 10000
France
Bondy, France, 93143
Bordeaux, France, 33000
Clichy, France, 92110
Dijon, France, 21000
Lille Cedex, France, 59020
Marseille, France, 13005
Nantes, France, 44805
Paris, France, 75020
Rennes Cedex, France, 35062
Vandoeuvre-les-nancy, France, 54500
Germany
Freiburg, Baden-Württemberg, Germany, 79106
Tübingen, Baden-Württemberg, Germany, 72076
München, Bayern, Germany, 81377
München, Bayern, Germany, 81675
Regensburg, Bayern, Germany, 93042
Frankfurt, Hessen, Germany, 60590
Hannover, Niedersachsen, Germany, 30625
Bonn, Nordrhein-Westfalen, Germany, 53105
Düsseldorf, Nordrhein-Westfalen, Germany, 40225
Essen, Nordrhein-Westfalen, Germany, 45122
Mainz, Rheinland-Pfalz, Germany, 55131
Homburg, Saarland, Germany, 66421
Halle, Sachsen-Anhalt, Germany, 06120
Magdeburg, Sachsen-Anhalt, Germany, 39120
Berlin, Germany, 12200
Hamburg, Germany, 20246
Greece
Haidari, Attica, Greece, 12462
Athens, Greece, 115 27
Ioannina, Greece, 45500
Thessaloniki, Greece, 540 07
Thessaloniki, Greece, 54639
Thessaloniki, Greece, 56403
Israel
Haifa, Israel, 84801
Petach Tikva, Israel, 49100
Tel Aviv, Israel, 64239
Zrifin, Israel, 70300
Italy
Rozzano, Milano, Italy, 20089
Avellino, Italy, 83100
Bologna, Italy, 40138
Forlì, Italy, 47100
Milano, Italy, 20122
Milano, Italy, 20133
Padova, Italy, 35128
Palermo, Italy, 90127
Pavia, Italy, 27100
Pisa, Italy, 56126
Roma, Italy, 00144
Mexico
México, Distrito Federal, Mexico, 14080
Monterrey, Mexico, 64000
México, D.F., Mexico, 06720
México, D.F., Mexico, 14050
New Zealand
Auckland, New Zealand, 1023
Wellington South, New Zealand, 6001
Peru
Comas Lima, Peru
Lima Cercado, Peru, LIMA 1
Lima, Peru, LIMA 34
Poland
Gdansk, Poland, 80-952
Poznan, Poland, 61-878
Warszawa, Poland, 02-507
Warszawa, Poland, 02-781
Romania
Timisoara, Timis, Romania, 300223
Craiova Dolj, Romania, 200642
Iasi, Romania, 700111
Russian Federation
Ekaterinburg, Russian Federation, 620036
Ekaterinburg, Russian Federation, 620102
Kazan, Russian Federation, 420012
Kirov, Russian Federation, 610002
Krasnodar, Russian Federation, 350040
Moscow, Russian Federation, 105 203
Moscow, Russian Federation, 105229
Moscow, Russian Federation, 111 020
Moscow, Russian Federation, 113 811
Moscow, Russian Federation, 115478
Moscow, Russian Federation, 129 010
Moscow, Russian Federation, 129110
St. Petersburg, Russian Federation, 188663
St. Petersburg, Russian Federation, 195 067
St. Petersburg, Russian Federation, 197758
Tolgliatti, Russian Federation
Spain
Badalona, Barcelona, Spain, 08916
Cruces/Barakaldo, Bilbao, Spain, 48903
Alicante, Spain, 03010
Barcelona, Spain, 08003
Barcelona, Spain, 08035
Barcelona, Spain, 08036
Córdoba, Spain, 14004
Madrid, Spain, 28006
Madrid, Spain, 28034
Madrid, Spain, 28041
Pamplona, Spain, 31008
Valencia, Spain, 46014
Switzerland
St. Gallen, Sankt Gallen, Switzerland, 9007
Bern, Switzerland, 3010
Genève, Switzerland, 1211
Zürich, Switzerland, 8091
United Kingdom
Bristol, Avon, United Kingdom, BS2 8ED
Oxford, Oxfordshire, United Kingdom, OX1 2JD
Glasgow, Stratchclyde, United Kingdom, G11 6NT
London, United Kingdom, NW3 2QG
London, United Kingdom, SE1 9RT
Newcastle-upon-Tyne, United Kingdom, NE2 4HH
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer

Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00105443     History of Changes
Other Study ID Numbers: 100554
2004-001773-26 ( EudraCT Number )
First Posted: March 15, 2005    Key Record Dates
Results First Posted: September 27, 2010
Last Update Posted: October 31, 2014
Last Verified: October 2014

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
Niacinamide
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs