A Phase II Randomized, Double-blind, Placebo-controlled Study of Sorafenib or Placebo in Combination With Transarterial Chemoembolization (TACE) Performed With DC Bead and Doxorubicin for Intermediate Stage Hepatocellular Carcinoma (HCC).

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00855218
First received: March 3, 2009
Last updated: July 15, 2014
Last verified: July 2014
  Purpose

This study will look at whether our drug (sorafenib) in combination with chemotherapy delivered directly into your tumor using beads (DC Bead) will slow the progression of the disease. The beads used with the chemotherapy will slowly release the chemotherapy reducing the adverse effects that normally occur with chemotherapy.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Double-blind, Placebo-controlled Study of Sorafenib or Placebo in Combination With Transarterial Chemoembolization (TACE) Performed With DC Bead and Doxorubicin for Intermediate Stage Hepatocellular Carcinoma (HCC).

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Time to Progression (TTP) - Independent Radiological Review (Primary Analysis) [ Time Frame: From randomization of the first participant until 28 months later (cut-off date) ] [ Designated as safety issue: No ]
    TTP is defined as the time (days) from randomization to radiological confirmed disease progression. Participants without progression at the time of analysis were censored at their last date of tumor evaluation.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: From randomization of the first participant until 28 months later (cut-off date) ] [ Designated as safety issue: No ]
    Overall Survival (OS) was defined as the time (days) from randomization to death due to any cause. Participants still alive at the time of analysis were censored at their last date of last contact.

  • Time to Untreatable Progression (TTUP) [ Time Frame: From randomization of the first participant until 28 months later (cut-off date) ] [ Designated as safety issue: No ]
    Time to untreatable progression (TTUP) was defined as the time (days) from randomization to untreatable progression. Participants without untreatable progression at the time of analysis were censored at their last date of tumor evaluation.

  • Time to Vascular Invasion/Extrahepatic Spread (TTVI/ES) [ Time Frame: From randomization of the first participant until 28 months later (cut-off date) ] [ Designated as safety issue: No ]
    Time to vascular invasion/extrahepatic spread (TTVI/ES) was defined as the time (days) from randomization to vascular invasion/extrahepatic spread. Participants without vascular invasion/extrahepatic spread at the time of analysis were censored at their last date of tumor evaluation.

  • Tumor Response - Independent Radiological Review [ Time Frame: From randomization of the first participant until 28 months later (cut-off date) ] [ Designated as safety issue: No ]
    Tumor Response was defined as the number of participants with a confirmed Complete Response (CR)=disappearance of all clinical and radiological tumor lesions, Partial Response (PR)= at least 30% decrease in sum of the longest diameters (LD) of tumor lesions, Stable Disease (SD)= neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease, or Progressive Disease (PD)=at least 20% increase in the sum of LD of measured lesions, observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

  • Tumor Response - Investigator Assessment [ Time Frame: From randomization of the first participant until 28 months later (cut-off date) ] [ Designated as safety issue: No ]
    Tumor Response was defined as the number of participants with a confirmed Complete Response (CR)=disappearance of all clinical and radiological tumor lesions, Partial Response (PR)= at least 30% decrease in sum of the longest diameters (LD) of tumor lesions, Stable Disease (SD)= neither sufficient shrinkage to qualify for PR nor sufficient increase for progressive disease, or Progressive Disease (PD)=at least 20% increase in the sum of LD of measured lesions, observed during trial period assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) criteria.


Enrollment: 307
Study Start Date: March 2009
Study Completion Date: February 2013
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib (Nexavar, BAY43-9006) + TACE
Sorafenib was to be orally administered as 2 x 200 mg tablets bid (twice daily). Patients were then also treated with Transarterial Chemoembolization (TACE) performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of sorafenib, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Drug: Sorafenib (Nexavar, BAY43-9006)
800 mg sorafenib (4 tablets) will be taken daily (400mg b.i.d. [twice daily], 2 tablets). Transarterial Chemoembolization (TACE) using DC Bead
Placebo Comparator: Placebo + TACE
Placebo was to be orally administered as 2 tablets bid (twice daily). Patients were then also treated with TACE performed with DC Bead (300 to 500 microns) and doxorubicin (150 mg) between 3 to 7 days after the first dose of placebo, TACE was also performed on Days 1 (+ 4 days) of cycle 1, 3, 7, 13 and then every 6 cycles thereafter (an optional TACE procedure could be performed between Day 1 of Cycle 7 and Cycle 13 and between Day 1 of Cycles 13 and 19, if deemed necessary by the Investigator.)
Drug: Placebo
4 tablets of placebo will be taken daily (2 tablets b.i.d). TACE using DC Bead

Detailed Description:

Safety issues will be reported in Adverse Event section. In addition to the secondary outcome measures, Biomarkers and Patient Report Outcome will also be analyzed as other variables.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Unresectable, multinodular asymptomatic tumor without vascular invasion or extrahepatic spread
  • Confirmed Diagnosis of HCC:
  • Cirrhotic subjects: Clinical diagnosis by American Association for the Study of Liver Diseases (AASLD) criteria
  • HCC can be defined in cirrhotic subjects by one imaging technique (Computed tomography [CT] scan, Magnetic resonance imaging [MRI], or second generation contrast ultrasound) showing a nodule larger than 2 cm with contrast uptake in the arterial phase and washout in venous or late phases or two imaging techniques showing this radiological behavior for nodules of 1-2 cm in diameter.
  • Cytohistological confirmation is required for subjects who do not fulfill these eligibility criteria.
  • Non-cirrhotic subjects:

For subjects without cirrhosis, histological or cytological confirmation is mandatory

  • Documentation of original biopsy for diagnosis is acceptable
  • Child Pugh class A without ascites
  • Adequate bone marrow, liver and renal function as assessed by central lab by means of the following laboratory requirements from samples within 7 days prior to randomization:

Exclusion Criteria:

  • Patients on a liver transplantation list or with advanced liver disease as defined below:
  • Child Pugh B and C
  • Active gastrointestinal bleeding
  • Encephalopathy
  • Ascites
  • Lesions having previously been treated with local therapy such as resection of HCC, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) or cryoablation can not be selected as the target lesions.
  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: NCT00855218

  Show 107 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
No publications provided

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00855218     History of Changes
Other Study ID Numbers: 12918, 2008-005056-24
Study First Received: March 3, 2009
Results First Received: August 23, 2012
Last Updated: July 15, 2014
Health Authority: Austria: Ethikkommission
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Institutional Review Board
Canada: Health Canada
China: Ministry of Health
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
Spain: Ministry of Health
Taiwan: Institutional Review Board
United States: Food and Drug Administration
Singapore: Health Sciences Authority
Korea: Food and Drug Administration

Keywords provided by Bayer:
Sorafenib
TACE
DC bead
Combination

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

ClinicalTrials.gov processed this record on August 21, 2014