Clinical trial NCT00108953: A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma
Official title: A Randomized Controlled Study of BAY43-9006 in Combination With Doxorubicin Versus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Keywords: Cancer
Liver Cancer
Hepatocellular carcinoma
HCC
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2005-04-22
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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

Primary outcomes:
measure: Time to Progression (TTP)
timeFrame: from date of randomization of the first patient until 3 years later
Secondary outcomes:
measure: Overall Survival
timeFrame: from date of randomization of the first patient until 3 years later
measure: Progression Free Survival (PFS)
timeFrame: from date of randomization of the first patient until 3 years later
measure: Percentage of Participants in Each Category of Best Tumor Response
timeFrame: achieved during treatment or within 30 days after termination of active therapy
measure: Time to Symptomatic Progression (TTSP)
timeFrame: from date of randomization of the first patient until 3 years later
measure: Duration of Response
timeFrame: from date of randomization of the first patient until 3 years later
measure: Time to Response (TTR)
timeFrame: from date of randomization until 3 years later at end of study
measure: Percentage of Participants for Whom Disease Control Was Achieved
timeFrame: from date of randomization to end of treatment plus 30 days
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Beverly Hills
country: United States
state: California
city: Orange
country: United States
state: California
city: Palo Alto
country: United States
state: California
city: San Francisco
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Sylmar
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Lafayette
country: United States
state: Louisiana
city: Minneapolis
country: United States
state: Minnesota
city: Hackensack
country: United States
state: New Jersey
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Nashville
country: United States
state: Tennessee
city: Seattle
country: United States
state: Washington
city: Buenos Aires
country: Argentina
state: Ciudad Auton. de Buenos Aires
city: Neuquen
country: Argentina
state: Neuquén
city: Buenos Aires
country: Argentina
city: Toronto
country: Canada
state: Ontario
city: Hong Kong
country: Hong Kong
city: Kazan
country: Russian Federation
city: Kirov
country: Russian Federation
city: Krasnodar
country: Russian Federation
city: Maidstone
country: United Kingdom
state: Kent
city: Bebington
country: United Kingdom
state: Merseyside
city: Birmingham
country: United Kingdom
state: West Midlands
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: 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. doi: 10.1200/JCO.2005.01.3441. Epub 2006 Aug 14.
citation: 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.