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).

July 18, 2017 updated by: Bayer
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

307

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
      • St Leonards, New South Wales, Australia, 2065
    • Queensland
      • Greenslopes, Queensland, Australia, 4120
    • Victoria
      • Clayton, Victoria, Australia, 3168
      • Heidelberg, Victoria, Australia, 3084
      • Melbourne, Victoria, Australia, 3004
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
  • Austria
      • Innsbruck, Austria, 6020
      • Wien, Austria, 1090
  • Belgium
      • Bruxelles - Brussel, Belgium, 1070
      • Bruxelles - Brussel, Belgium, 1200
      • Bruxelles - Brussel, Belgium, 1090
      • Leuven, Belgium, 3000
      • Liege, Belgium, 4000
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N1
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 2Y9
    • Ontario
      • Toronto, Ontario, Canada, M5G 2N2
  • China
      • Beijing, China, 100021
      • Beijing, China, 100142
      • Shanghai, China, 200032
      • Shanghai, China, 200438
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
      • Guangzhou, Guangdong, China, 510060
    • Shannxi
      • Xi'an, Shannxi, China, 710032
  • France
      • Creteil, France, 94010
      • Lille, France, 59037
      • Lyon, France, 69003
      • Lyon Cedex, France, 69288
      • Marseille, France, 13005
      • Paris, France, 75571
      • Paris, France, 75020
      • Vandoeuvre-les-nancy, France, 54500
      • Villejuif, France, 94800
      • Villejuif, France, 94805
  • Germany
      • Berlin, Germany, 13353
      • Hamburg, Germany, 20246
    • Baden-Württemberg
      • Freiburg, Baden-Württemberg, Germany, 79106
      • Heidelberg, Baden-Württemberg, Germany, 69120
      • Tübingen, Baden-Württemberg, Germany, 72076
    • Bayern
      • Erlangen, Bayern, Germany, 91054
      • München, Bayern, Germany, 81377
      • Regensburg, Bayern, Germany, 93042
    • Hessen
      • Frankfurt, Hessen, Germany, 60590
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30625
    • Nordrhein-Westfalen
      • Essen, Nordrhein-Westfalen, Germany, 45147
      • Essen, Nordrhein-Westfalen, Germany, 45136
      • Münster, Nordrhein-Westfalen, Germany, 48149
    • Rheinland-Pfalz
      • Mainz, Rheinland-Pfalz, Germany, 55131
    • Saarland
      • Homburg, Saarland, Germany, 66421
    • Thüringen
      • Jena, Thüringen, Germany, 07743
  • Italy
    • Campania
      • Napoli, Campania, Italy, 80131
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
    • Lazio
      • Roma, Lazio, Italy, 00133
      • Roma, Lazio, Italy, 00185
    • Lombardia
      • Milano, Lombardia, Italy, 20133
      • Milano, Lombardia, Italy, 20122
    • Piemonte
      • Torino, Piemonte, Italy, 10126
    • Puglia
      • Bari, Puglia, Italy, 70021
    • Sicilia
      • Palermo, Sicilia, Italy, 90127
    • Toscana
      • Pisa, Toscana, Italy, 56124
    • Veneto
      • Padova, Veneto, Italy, 35128
      • Verona, Veneto, Italy, 37134
  • Korea, Republic of
      • Daegu, Korea, Republic of, 700-721
      • Gyeonggi-do, Korea, Republic of, 411-706
      • Seoul, Korea, Republic of, 110-744
      • Seoul, Korea, Republic of, 120-752
      • Seoul, Korea, Republic of, 135-710
      • Seoul, Korea, Republic of, 135-720
        • Gangnam Severance Hospital, Yonsei University
  • Singapore
      • Singapore, Singapore, 119228
      • Singapore, Singapore, 169610
  • Spain
      • A Coruña, Spain, 15006
      • Alicante, Spain, 03010
      • Barcelona, Spain, 08036
      • Córdoba, Spain, 14004
      • Madrid, Spain, 28046
      • Madrid, Spain, 28034
      • Sevilla, Spain, 41013
        • Hospital Universitario Virgen Del Rocio
      • Valencia, Spain, 46014
    • A Coruña
      • Santiago de Compostela, A Coruña, Spain, 15706
    • Asturias
      • Oviedo, Asturias, Spain, 33006
        • Hospital Central de Asturias
    • Barcelona
      • Badalona, Barcelona, Spain, 08916
      • Sabadell, Barcelona, Spain, 08208
    • Bilbao
      • Cruces/Barakaldo, Bilbao, Spain, 48903
    • Catalunya
      • Barcelona, Catalunya, Spain, 08035
    • Madrid
      • Alcorcón, Madrid, Spain, 28922
        • Fundación Hospital Alcorcón
    • Santa Cruz de Tenerife
      • La Laguna, Santa Cruz de Tenerife, Spain, 38320
  • Taiwan
      • Changhua, Taiwan, 500
        • Changhua Christian Hospital
      • Taipei, Taiwan, 11217
      • Taipei, Taiwan, 10002
  • United States
    • California
      • La Jolla, California, United States, 92037
      • Los Angeles, California, United States, 90095-7077
      • San Francisco, California, United States, 94115
    • Florida
      • Gainesville, Florida, United States, 32610-0316
      • Miami, Florida, United States, 33136
      • Orlando, Florida, United States, 32804
    • Georgia
      • Atlanta, Georgia, United States, 30309-1231
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0330
      • Detroit, Michigan, United States, 48202
    • Minnesota
      • Minneapolis, Minnesota, United States, 55407
        • Abbott Northwestern Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63104
    • New York
      • New York, New York, United States, 10029
    • Ohio
      • Cleveland, Ohio, United States, 44195
      • Columbus, Ohio, United States, 43210-1240
    • Oregon
      • Portland, Oregon, United States, 97239
    • Virginia
      • Richmond, Virginia, United States, 23249
    • Washington
      • Seattle, Washington, United States, 98101
      • Seattle, Washington, United States, 98109-1023

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Progression (TTP) - Independent Radiological Review (Primary Analysis)
Time Frame: From randomization of the first participant until 28 months later (cut-off date)
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.
From randomization of the first participant until 28 months later (cut-off date)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: From randomization of the first participant until 28 months later (cut-off date)
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.
From randomization of the first participant until 28 months later (cut-off date)
Time to Untreatable Progression (TTUP)
Time Frame: From randomization of the first participant until 28 months later (cut-off date)
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.
From randomization of the first participant until 28 months later (cut-off date)
Time to Vascular Invasion/Extrahepatic Spread (TTVI/ES)
Time Frame: From randomization of the first participant until 28 months later (cut-off date)
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.
From randomization of the first participant until 28 months later (cut-off date)
Tumor Response - Independent Radiological Review
Time Frame: From randomization of the first participant until 28 months later (cut-off date)
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.
From randomization of the first participant until 28 months later (cut-off date)
Tumor Response - Investigator Assessment
Time Frame: From randomization of the first participant until 28 months later (cut-off date)
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.
From randomization of the first participant until 28 months later (cut-off date)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2009

Primary Completion (Actual)

July 1, 2011

Study Completion (Actual)

February 1, 2013

Study Registration Dates

First Submitted

March 3, 2009

First Submitted That Met QC Criteria

March 3, 2009

First Posted (Estimate)

March 4, 2009

Study Record Updates

Last Update Posted (Actual)

August 18, 2017

Last Update Submitted That Met QC Criteria

July 18, 2017

Last Verified

July 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12918
  • 2008-005056-24 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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