A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma

Bayer

Status and phase: Completed; Phase 2

Conditions: Carcinoma, Hepatocellular

Treatments: Drug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin; Drug: Doxorubicin/Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT00108953

11546 (Registry Identifier)

2004-001770-40 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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).

Enrollment: 96 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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96 participants in 2 patient groups

Sorafenib + Doxorubicin

Experimental group

Description:

"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)

Treatment:

Drug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin

Placebo + Doxorubicin

Active Comparator group

Description:

"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)

Treatment:

Drug: Doxorubicin/Placebo