A Research Study to Treat Patients With Advanced Hepatocellular Carcinoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00108953
First received: April 21, 2005
Last updated: March 26, 2014
Last verified: March 2014
  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).


Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin
Drug: Doxorubicin/Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Study of BAY43-9006 in Combination With Doxorubicin Versus Doxorubicin in Patients With Advanced Hepatocellular Carcinoma.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Time 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.


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)


Enrollment: 96
Study Start Date: April 2005
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Drug: Sorafenib (Nexavar, BAY43-9006) plus Doxorubicin
Multi kinase inhibitor plus Chemotherapy
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)
Drug: Doxorubicin/Placebo
Chemotherapy plus Placebo

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00108953

  Show 28 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00108953     History of Changes
Other Study ID Numbers: 11546, 2004-001770-40
Study First Received: April 21, 2005
Results First Received: April 23, 2009
Last Updated: March 26, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Bayer:
Cancer
Liver Cancer
Hepatocellular carcinoma
HCC

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Liposomal doxorubicin
Doxorubicin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014