Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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25 November 2019 |
Main ID: |
EUCTR2012-003649-14-BE |
Date of registration:
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22/11/2012 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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This clinical study evaluates the efficacy and safety of regorafenib in patients with advanced liver cancer who have progressed on sorafenib treatment.
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Scientific title:
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A randomized, double blind, placebo-controlled, multicenter phase III study of regorafenib in patients with hepatocellular carcinoma (HCC) after sorafenib |
Date of first enrolment:
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20/03/2013 |
Target sample size:
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530 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-003649-14 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Argentina
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Australia
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Austria
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Belgium
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Brazil
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China
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Czech Republic
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France
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Germany
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Hungary
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Israel
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Italy
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Japan
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Korea, Republic of
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Netherlands
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Russian Federation
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Singapore
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Spain
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Switzerland
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Taiwan
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United Kingdom
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United States
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Contacts
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Name:
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Clinical Trials Contact
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Address:
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CTP Team/Ref 'EU CTR'/Bayer Pharma AG
13342
Berlin
Germany |
Telephone:
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Email:
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clinical-trials-contact@bayerhealthcare.com |
Affiliation:
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Bayer HealthCare AG |
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Name:
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Clinical Trials Contact
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Address:
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CTP Team/Ref 'EU CTR'/Bayer Pharma AG
13342
Berlin
Germany |
Telephone:
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Email:
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clinical-trials-contact@bayerhealthcare.com |
Affiliation:
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Bayer HealthCare AG |
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Key inclusion & exclusion criteria
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Inclusion criteria: • Signed informed consent (IC) obtained before any study specific procedure. Patients must be able to understand and willing to sign the written informed consent.
• Male or female patients =18 years of age.
• Histological or cytological confirmation of HCC or non-invasive diagnosis of HCC as per American Association for the Study of Liver Diseases (AASLD) criteria in patients with a confirmed diagnosis of cirrhosis.
• Barcelona Clinic Liver Cancer (BCLC) stage Category B or C that cannot benefit from treatments of established efficacy with higher priority such as resection, liver transplantation, local ablation, chemoembolization or systemic sorafenib.
• Failure to prior treatment with sorafenib (defined as documented radiological progression according to the radiology charter). Randomization needs to be performed within 8 weeks after the last treatment with sorafenib.
• Tolerability of prior treatment with sorafenib defined as not less than 20 days at a minimum daily dose of 400 mg QD within the last 28 days prior to withdrawal.
• Liver function status Child-Pugh Class A. Child Pugh status should be calculated based on clinical findings and laboratory results during the screening period.
• Local or loco-regional therapy (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed = 4 weeks before first dose of study medication.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory tests conducted within 7 days before randomization:
o Hemoglobin > 8.5 g/dl
o Absolute neutrophil count (ANC) = 1500/mm3
o Platelet count = 60.000/mm3
o Total bilirubin = 2 mg/dl. Mildly elevated total bilirubin (<6 mg/dL) is allowed if Gilbert’s syndrome is documented.
o Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 5 x upper limit of normal (ULN)
o Prothrombin time-international normalized ratio (PT-INR) < 2.3 x (ULN). Patients who are therapeutically anticoagulated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in this parameter exists. Close monitoring of at least weekly evaluations will be performed until INR is stable based on a measurement that is pre-dose as defined by the local standard of care.
o Serum creatinine = 1.5 x ULN
o Amylase and lipase = 2 x ULN
• Glomerular filtration rate (GFR) = 30 ml/min/1.73 m2 according to the Modification of diet in renal disease (MDRD) abbreviated formula
• At least one uni-dimensional measurable lesion by computed
tomography (CT) scan or magnetic resonance imaging (MRI) according
to RECIST (RECIST version 1.1), and modified RECIST for HCC. Tumor
lesions situated in a previously irradiated area, or in an area subjected to
other loco-regional therapy, may be considered measurable if there has
been demonstrated progression in the lesion.
• Life expe
Exclusion criteria: • Prior liver transplantation or candidates for liver transplantation
• Prior treatment with regorafenib. Patients permanently withdrawn from study participation will not be allowed to re-enter the study.
• Prior and/or concomitant participation in a clinical study other than with sorafenib during or within 4 weeks of randomization.
• Sorafenib treatment within 2 weeks of randomization.
• Patients with large esophageal varices at risk of bleeding that are not
being treated with conventional medical intervention: beta blockers or
endoscopic treatment. Assessment of esophageal varices for patients in
whom conventional medical intervention for known esophageal varices
is already in place should be performed by endoscopy as per local
standard of care.
• Prior systemic treatment for HCC, except sorafenib.
• Permanent discontinuation of prior sorafenib therapy due to sorafenib related toxicity.
• Permanent discontinuation of prior sorafenib therapy due to any cause more than 8 weeks prior to randomization.
• Past or concurrent history of neoplasm other than HCC, except for in situ carcinoma of the cervix uteri and/or basal cell epithelioma. Any cancer curatively treated > 3 years prior to study entry is permitted.
• Known history or symptomatic metastatic brain or meningeal tumors (head CT or MRI at screening to confirm the absence of central nervous system [CNS] disease if patient has symptoms suggestive or consistent with CNS disease).
• Major surgical procedure or significant traumatic injury within 28 days before randomization.
• Congestive heart failure New York Heart Association (NYHA) = class 2
• Unstable angina (angina symptoms at rest, new-onset angina i.e., within the last 3 months) or myocardial infarction (MI) within the past 6 months before randomization.
• Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
• Uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
• Patients with phaeochromocytoma.
• Uncontrolled ascites (defined as not easily controlled with diuretic or paracentesis treatment).
• Pleural effusion or ascites that causes respiratory compromise (NCI-CTCAE version 4.0 Grade =2 dyspnea).
• Persistent proteinuria of NCI-CTCAE version 4.0 Grade 3 or higher. Urine dipstick result of 3+ is allowed if protein excretion (estimated by urine protein/creatinine ratio on a random urine sample) is < 3.5 g/24 hours.
• Ongoing infection > Grade 2 according to NCI-CTCAE version 4.0.
Hepatitis B is allowed if no active replication is present. Hepatitis C is
allowed if no antiviral treatment is required.
• Clinically significant bleeding NCI-CTCAE version 4.0 Grade 3 or higher within 30 days before randomization.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months before the start of study medicatio
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Hepatocellular carcinoma (HCC)
MedDRA version: 16.0
Level: LLT
Classification code 10019829
Term: Hepatocellular carcinoma recurrent
System Organ Class: 100000004864
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Therapeutic area: Diseases [C] - Cancer [C04]
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Intervention(s)
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Trade Name: Stivarga Product Name: Regorafenib Product Code: BAY 73-4506 Pharmaceutical Form: Film-coated tablet INN or Proposed INN: Regorafenib CAS Number: 755037-03-7 Current Sponsor code: BAY 73-4506 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 40- Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use
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Primary Outcome(s)
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Main Objective: The objective of this study is to evaluate efficacy and safety of regorafenib in patients with HCC who have progressed after sorafenib
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Secondary Objective: None
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Timepoint(s) of evaluation of this end point: The time (days) from date of first dose of study medication to death due to any cause
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Primary end point(s): Overall survival (OS)
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Secondary Outcome(s)
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Secondary end point(s): • Time to progression (TTP)
• Progression free survival (PFS)
• Objective tumor response rate (ORR)
• Disease control rate (DCR = CR + PR + SD)
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Timepoint(s) of evaluation of this end point: Approximately 33 months
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Secondary ID(s)
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2012-003649-14-DE
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BAY73-4506/15982
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Source(s) of Monetary Support
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Bayer HealthCare AG
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Ethics review
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Status: Approved
Approval date:
Contact:
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