A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma

Overview[ - collapse ][ - ]

Purpose 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).
ConditionCarcinoma, Hepatocellular
InterventionDrug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin
Drug: Doxorubicin/Placebo
PhasePhase 2
SponsorBayer
Responsible PartyBayer
ClinicalTrials.gov IdentifierNCT00108953
First ReceivedApril 21, 2005
Last UpdatedMarch 26, 2014
Last verifiedMarch 2014

Tracking Information[ + expand ][ + ]

First Received DateApril 21, 2005
Last Updated DateMarch 26, 2014
Start DateApril 2005
Estimated Primary Completion DateApril 2008
Current Primary Outcome MeasuresTime to Progression (TTP) [Time Frame: from date of randomization of the first patient until 3 years later] [Designated as safety issue: No]TTP was defined as the time from randomization to radiological disease progression by independent assessment.
Current Secondary Outcome Measures
  • Overall Survival [Time Frame: from date of randomization of the first patient until 3 years later] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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)

Descriptive Information[ + expand ][ + ]

Brief TitleA Research Study to Treat Patients With Advanced Hepatocellular Carcinoma
Official TitleA 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 TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
ConditionCarcinoma, Hepatocellular
InterventionDrug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin
Multi kinase inhibitor plus Chemotherapy
Drug: Doxorubicin/Placebo
Chemotherapy plus Placebo
Study Arm (s)
  • 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)
  • 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)

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment96
Estimated Completion DateApril 2008
Estimated Primary Completion DateApril 2008
Eligibility Criteria
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
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States, Argentina, Canada, Hong Kong, Russian Federation, United Kingdom

Administrative Information[ + expand ][ + ]

NCT Number NCT00108953
Other Study ID Numbers11546
Has Data Monitoring CommitteeNo
Information Provided ByBayer
Study SponsorBayer
CollaboratorsNot Provided
Investigators Study Director: Bayer Study Director Bayer
Verification DateMarch 2014

Locations[ + expand ][ + ]

United States, Alabama
Birmingham, Alabama, United States, 35294
United States, California
Beverly Hills, California, United States, 90211-1850
United States, California
Orange, California, United States, 92668-3298
United States, California
Palo Alto, California, United States, 94304-1207
United States, California
San Francisco, California, United States, 94115
United States, California
San Francisco, California, United States, 94121
United States, California
Sylmar, California, United States, 91342
United States, Florida
Miami, Florida, United States, 33136
United States, Louisiana
Lafayette, Louisiana, United States, 70506
United States, Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New Jersey
Hackensack, New Jersey, United States, 07601
United States, New York
New York, New York, United States, 10065
United States, New York
Rochester, New York, United States, 14642
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Washington
Seattle, Washington, United States, 98101
Argentina, Ciudad Auton. de Buenos Aires
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1264AAA
Argentina, Neuquén
Neuquen, Neuquén, Argentina, Q8300HDH
Argentina
Buenos Aires, Argentina
Canada, Ontario
Toronto, Ontario, Canada, M5G 2M9
Hong Kong
Hong Kong, Hong Kong
Russian Federation
Kazan, Russian Federation, 420111
Russian Federation
Kirov, Russian Federation, 610002
Russian Federation
Krasnodar, Russian Federation, 350040
United Kingdom, Kent
Maidstone, Kent, United Kingdom, ME16 9QQ
United Kingdom, Merseyside
Bebington, Merseyside, United Kingdom, CH63 4JY
United Kingdom, West Midlands
Birmingham, West Midlands, United Kingdom, B15 2TT
United Kingdom
London, United Kingdom, W12 0HS
United Kingdom
Manchester, United Kingdom, M20 4BX