A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma

Tracking Information
First Submitted Date ICMJE	April 21, 2005
First Posted Date ICMJE	April 22, 2005
Results First Submitted Date	April 23, 2009
Results First Posted Date	June 11, 2009
Last Update Posted Date	October 31, 2014
Study Start Date ICMJE	April 2005
Actual Primary Completion Date	April 2008 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: March 11, 2011)	Time to Progression (TTP) [ Time Frame: from date of randomization of the first patient until 3 years later ]; TTP was defined as the time from randomization to radiological disease progression by independent assessment.
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00108953 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: March 11, 2011)	Overall Survival [ Time Frame: from date of randomization of the first patient until 3 years later ]The time from date of randomization to date of death; Progression Free Survival (PFS) [ Time Frame: from date of randomization of the first patient until 3 years later ]Time from the date of randomization to the date of the first documented radiological progression (as defined per independent central radiological assessment) or death, whichever occurs first; Percentage of Participants in Each Category of Best Tumor Response [ Time Frame: achieved during treatment or within 30 days after termination of active therapy ]Percentage of participants with complete or partial response (CR or PR) confirmed according to Response Evaluation Criteria in Solid Tumors (RECIST) and achieved during treatment or 30 days after end of treatment. CR: disappearance of all clinical and radiological tumor lesions. PR: at least 30% decrease in sum of the longest diameters of tumor lesions. Stable disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease.; Time to Symptomatic Progression (TTSP) [ Time Frame: from date of randomization of the first patient until 3 years later ]Time from date of randomization to date of first documented symptomatic progression defined by Functional Assessment of Cancer Therapy Hepatobiliary Symptom Index-8 (FHSI-8) assessment; Duration of Response [ Time Frame: from date of randomization of the first patient until 3 years later ]Time from date of first objective response (complete response [CR] or partial response [PR]) to date progression is first documented (as defined per independent central radiological assessment) or death, whichever occurs first; Time to Response (TTR) [ Time Frame: from date of randomization until 3 years later at end of study ]Time from date of randomization to date of first objective response (complete response [CR] or partial response [PR]) is documented and confirmed according to RECIST criteria; Percentage of Participants for Whom Disease Control Was Achieved [ Time Frame: from date of randomization to end of treatment plus 30 days ]Participants with disease control: those who have as best response complete response (CR), partial response (PR) or stable disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease) according to Response Evaluation Criteria in Solid Tumors (RECIST)
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma
Official Title ICMJE	A Randomized Controlled Study of BAY43-9006 in Combination With Doxorubicin Versus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma.
Brief Summary	The purpose of this study is to evaluate the safety and efficacy of doxorubicin plus sorafenib versus doxorubicin plus placebo in patients with advanced hepatocellular carcinoma (HCC).
Detailed Description	In addition to the key secondary outcome parameters the following parameters will be assessed in an exploratory manner: relative time to progression (TTP), time to symptomatic progression (TTSP), response rate (RR) and overall survival between the 2 study populations. The possible and potential predictive assays of clinical benefit through an assessment of the correlation between the defined baseline characteristics and key clinical endpoints. The safety and tolerability will be assessed in the adverse event section. Doxorubicin pharmacokinetics in HCC patients treated with sorafenib versus placebo will be compared and the pharmacokinetic data will be correlated with doxorubicin-related adverse events (i.e., cardiotoxicity).
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Carcinoma, Hepatocellular
Intervention ICMJE	Drug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin Multi kinase inhibitor plus Chemotherapy; Drug: Doxorubicin/Placebo Chemotherapy plus Placebo
Study Arms	Experimental: Sorafenib + Doxorubicin "Sorafenib + Doxorubicin" -- combination therapy: Sorafenib (Nexavar, BAY43-9006) 200 mg tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) Intervention: Drug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin; Active Comparator: Placebo + Doxorubicin "Placebo + Doxorubicin" -- monotherapy: Sorafenib (Nexavar, BAY43-9006) matching placebo tablets by mouth (orally) twice daily + doxorubicin 60 mg/m2 intravenous infusion every 21 days for 6 cycles (18 weeks) Intervention: Drug: Doxorubicin/Placebo
Publications *	Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, De Greve J, Douillard JY, Lathia C, Schwartz B, Taylor I, Moscovici M, Saltz LB. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2006 Sep 10;24(26):4293-300. Epub 2006 Aug 14.; Abou-Alfa GK, Johnson P, Knox JJ, Capanu M, Davidenko I, Lacava J, Leung T, Gansukh B, Saltz LB. Doxorubicin plus sorafenib vs doxorubicin alone in patients with advanced hepatocellular carcinoma: a randomized trial. JAMA. 2010 Nov 17;304(19):2154-60. doi: 10.1001/jama.2010.1672.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: June 26, 2007)	96
Original Enrollment ICMJE	Not Provided
Actual Study Completion Date	April 2008
Actual Primary Completion Date	April 2008 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Patients who have a life expectancy of at least 12 weeks; Patients with advanced HCC (unresectable, and/or metastatic) which has been histologically or cytologically documented; Patients must have at least one tumor lesion that meets both of the following criteria: can be accurately measured in at least one dimension according to Response Evaluation Criteria in Solid Tumors (RECIST) has not been previously treated with local therapy; Patients who have received local therapy except chemoembolization, such as surgery, radiation therapy, hepatic arterial embolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible, provided that they either have a target lesion which has not been subjected to local therapy and/or the target lesion(s) within the field of the local therapy has shown an increase of 25% in the size. Local therapy must be completed at least 4 weeks prior to the baseline scan; Patients who have an Eastern Cooperative Oncology Group (ECOG) 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, and superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted; History of cardiac disease; Serious myocardial dysfunction; Active, clinically serious infections; Known history of Human Immunodeficiency Virus (HIV) infection; Known Central Nervous System (CNS) tumors including metastatic brain disease; Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Argentina, Canada, Hong Kong, Russian Federation, United Kingdom, United States
Removed Location Countries	China
Administrative Information
NCT Number ICMJE	NCT00108953
Other Study ID Numbers ICMJE	11546; 2004-001770-40 ( EudraCT Number )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Bayer
Study Sponsor ICMJE	Bayer
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Bayer Study Director Bayer
PRS Account	Bayer
Verification Date	October 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP