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

NCT00105443 | Completed Phase 3 Results DMC

• 2 other identifiers: 1005542004-001773-26
• Study Type: interventional
• Target: 602
• Locations: 23 countries
• Sites: 178

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.

Conditions

Carcinoma, Hepatocellular

Keywords

Liver Cancer; Cancer

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (3)

• Time to Progression (TTP)

  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

• Disease Control (DC)

  time from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment

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

  from randomization to end of treatment up to the data cutoff date approximately 19 months after start of enrollment

Study Arms (2)

Sorafenib (Nexavar, BAY43-9006)

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

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

Interventions

Sorafenib (Nexavar, BAY43-9006) DRUG

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.

Sorafenib (Nexavar, BAY43-9006)

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bayer: lead

Study Sites (178)

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Phoenix, Arizona, 85054-4502, United States

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Tucson, Arizona, 85724, United States

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Los Angeles, California, 90057, United States

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Los Angeles, California, 90095-7077, United States

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Orange, California, 92668-3298, United States

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San Francisco, California, 94121, United States

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Stanford, California, 94305, United States

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Farmington, Connecticut, 06030, United States

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New Haven, Connecticut, 06510-8019, United States

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Gainesville, Florida, 32610, United States

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Miami, Florida, 33136, United States

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Tampa, Florida, 33612, United States

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Atlanta, Georgia, 30308, United States

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Atlanta, Georgia, 30322, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60612, United States

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Lexington, Kentucky, 40536, United States

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Ann Arbor, Michigan, 48109-0362, United States

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Detroit, Michigan, 48202-2689, United States

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St Louis, Missouri, 63104, United States

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Omaha, Nebraska, 68198-2000, United States

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Manhasset, New York, 11030-3876, United States

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New York, New York, 10016, United States

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New York, New York, 10021, United States

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New York, New York, 10029, United States

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New York, New York, 10032, United States

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Canton, Ohio, 44718, United States

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Portland, Oregon, 97239, United States

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Philadelphia, Pennsylvania, 19104, United States

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Philadelphia, Pennsylvania, 19140, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Houston, Texas, 77030-1502, United States

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Richmond, Virginia, 23249, United States

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Seattle, Washington, 98104, United States

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Seattle, Washington, 98195-6174, United States

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Mar del Plata, Buenos Aires, 7600, Argentina

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Pilar, Buenos Aires, B1629AHJ, Argentina

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Bueno Aires, Ciudad Auton. de Buenos Aires, C1417DTB, Argentina

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Buenos Aires, Ciudad Auton. de Buenos Aires, C1120AAF, Argentina

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Buenos Aires, Ciudad Auton. de Buenos Aires, C1145ADP, Argentina

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Buenos Aires, Ciudad Auton. de Buenos Aires, C1181ACH, Argentina

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San Miguel de Tucumán, Tucumán Province, T4000GTB, Argentina

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San Miguel de Tucumán, Tucumán Province, T4000HXU, Argentina

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Camperdown, New South Wales, 2050, Australia

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Randwick, New South Wales, 2031, Australia

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Westmead, New South Wales, 2145, Australia

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East Bentleigh, Victoria, 3165, Australia

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Heidelberg, Victoria, 3084, Australia

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Melbourne, Victoria, 3052, Australia

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Bruges, 8000, Belgium

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Bruxelles - Brussel, 1070, Belgium

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Bruxelles - Brussel, 1090, Belgium

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Bruxelles - Brussel, 1200, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

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Porto Alegre, Rio Grande do Sul, 90619900, Brazil

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São Paulo, São Paulo, 01246-903, Brazil

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Belo Horizonte, 30180090, Brazil

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Belo Horizonte, 30380490, Brazil

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Sofia, 1233, Bulgaria

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Sofia, 1431, Bulgaria

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Sofia, 1527, Bulgaria

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Stara Zagora, 6000, Bulgaria

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Varna, 9010, Bulgaria

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Calgary, Alberta, T2N 4N1, Canada

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Edmonton, Alberta, T6G 2C8, Canada

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Vancouver, British Columbia, V5Z 1H8, Canada

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Winnipeg, Manitoba, R2H 2A6, Canada

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London, Ontario, N6A 5A5, Canada

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Ottawa, Ontario, K1H 1C4, Canada

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Toronto, Ontario, M5G 2N2, Canada

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Montreal, Quebec, H3A 1A1, Canada

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Santiago, Santiago Metropolitan, 833-0024, Chile

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Santiago, Chile

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Santiago Región Metropolitana, Chile

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Zagreb, 10000, Croatia

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Bondy, 93143, France

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Bordeaux, 33000, France

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Clichy, 92110, France

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Dijon, 21000, France

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Lille, 59020, France

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Marseille, 13005, France

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Nantes, 44805, France

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Paris, 75020, France

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Rennes, 35062, France

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Vandœuvre-lès-Nancy, 54500, France

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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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Tübingen, Baden-Wurttemberg, 72076, Germany

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München, Bavaria, 81377, Germany

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München, Bavaria, 81675, Germany

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Regensburg, Bavaria, 93042, Germany

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Hamburg, Hamburg, 20246, Germany

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Frankfurt am Main, Hesse, 60590, Germany

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Hanover, Lower Saxony, 30625, Germany

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Bonn, North Rhine-Westphalia, 53105, Germany

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Düsseldorf, North Rhine-Westphalia, 40225, Germany

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Essen, North Rhine-Westphalia, 45122, Germany

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Mainz, Rhineland-Palatinate, 55131, Germany

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Homburg, Saarland, 66421, Germany

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Halle, Saxony-Anhalt, 06120, Germany

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Magdeburg, Saxony-Anhalt, 39120, Germany

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Berlin, State of Berlin, 12200, Germany

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Haidari, Attica, 12462, Greece

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Thessaloniki, Thessaloniki, 54639, Greece

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Thessaloniki, Thessaloniki, 56403, Greece

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Athens, 115 27, Greece

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Ioannina, 45500, Greece

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Thessaloniki, 540 07, Greece

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Petah Tikva, Israel, 49100, Israel

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Tel Aviv, Israel, 64239, Israel

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Zrifin, Israel, 70300, Israel

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Haifa, 84801, Israel

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Forlì, Forlì, 47100, Italy

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Rozzano, Milano, 20089, Italy

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Avellino, 83100, Italy

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Bologna, 40138, Italy

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Milan, 20122, Italy

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Milan, 20133, Italy

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Padua, 35128, Italy

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Palermo, 90127, Italy

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Pavia, 27100, Italy

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Pisa, 56126, Italy

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Roma, 00144, Italy

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Mexico City, Mexico City, 14080, Mexico

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México, D.F., 06720, Mexico

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México, D.F., 14050, Mexico

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Monterrey, 64000, Mexico

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Auckland, 1023, New Zealand

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Wellington South, 6001, New Zealand

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Comas Lima, Peru

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Lima, LIMA 34, Peru

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Lima Cercado, LIMA 1, Peru

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Gdansk, 80-952, Poland

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Poznan, 61-878, Poland

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Warsaw, 02-507, Poland

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Warsaw, 02-781, Poland

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Iași, Iaşi, 700111, Romania

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Timișoara, Timiș County, 300223, Romania

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Craiova Dolj, 200642, Romania

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Kazan', 420012, Russia

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Kirov, 610002, Russia

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Krasnodar, 350040, Russia

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Moscow, 105 203, Russia

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Moscow, 105229, Russia

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Moscow, 111 020, Russia

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Moscow, 113 811, Russia

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Moscow, 115478, Russia

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Moscow, 129 010, Russia

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Moscow, 129110, Russia

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Saint Petersburg, 188663, Russia

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Saint Petersburg, 195 067, Russia

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Saint Petersburg, 197758, Russia

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Tolgliatti, Russia

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Yekaterinburg, 620036, Russia

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Yekaterinburg, 620102, Russia

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Alicante, Alicante, 03010, Spain

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Badalona, Barcelona, 08916, Spain

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Barcelona, Barcelona, 08003, Spain

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Barcelona, Barcelona, 08035, Spain

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Barcelona, Barcelona, 08036, Spain

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Cruces/Barakaldo, Bilbao, 48903, Spain

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Córdoba, Córdoba, 14004, Spain

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Madrid, Madrid, 28006, Spain

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Madrid, Madrid, 28034, Spain

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Madrid, Madrid, 28041, Spain

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Pamplona, Pamplona, 31008, Spain

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Valencia, Valencia, 46014, Spain

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Bern, Canton of Bern, 3010, Switzerland

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Geneva, Canton of Geneva, 1211, Switzerland

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Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

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Zurich, Canton of Zurich, 8091, Switzerland

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Bristol, Avon, BS2 8ED, United Kingdom

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London, London, NW3 2QG, United Kingdom

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London, London, SE1 9RT, United Kingdom

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Oxford, Oxfordshire, OX1 2JD, United Kingdom

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Glasgow, Stratchclyde, G11 6NT, United Kingdom

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Newcastle upon Tyne, NE2 4HH, United Kingdom

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Related Publications (3)

• 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 RESULT

• 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 DERIVED

• 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 DERIVED

Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms; Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayerhealthcare.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2005
• First Posted: March 15, 2005
• Study Start: March 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: October 31, 2014
• Results First Posted: September 27, 2010

Record last verified: 2014-10

Locations

CH (4); NZ (2); US (35); DE (16); GR (6); PE (3); GB (6); BR (5); CR (1); RO (3); AR (8); AU (6); BE (6); BU (5); CA (8); FR (10); IL (4); CL (3); IT (11); PL (4); ME (4); RU (16); ES (12)