Advanced hepatocellular carcinoma MedDRA version: 7.1 Level: LLT Classification code 10049010
Conditions
Interventions
Product Name: sorafenib
Product Code: BAY 43-9006
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: sorafenib
Current Sponsor code: BAY 43-9006
Other descriptive name: BAY 53-9085: sorafeni
Sponsors
Bayer HealthCare AG, D-51368 Leverkusen Germany
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Primary diagnosis Patients with advanced HCC, ECOG PS 0, 1, or 2, Child-Pugh status A, who have not received prior systemic anti-cancer treatment for HCC. Inclusion Criteria: •Male or female patients > 18 years of age •Patients who have a life expectancy of at least 12 weeks •Patients with advanced HCC •Patients with histologically or cytologically documented HCC (original biopsy at first diagnosis is acceptable) •Patients must have at least one tumor lesion that meets both of the following criteria: ? The lesion can be accurately measured in at least one dimension according to RECIST ? The lesion has not been previously treated with local therapy (such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) •Patients who have received local therapy, such as surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible. Previously treated lesions will not be selected as target lesions. Local therapy must be completed at least 4 weeks prior to the baseline scan. •Patients who have an ECOG PS of 0, 1, or 2 •Cirrhotic status of Child-Pugh class A only. Child-Pugh assessment is to be carried out during the screening period. The following laboratory parameters: ? Platelet count >= 60 x 109/L ? Hemoglobin >= 8.5 g/dL ? Total bilirubin = 2.8 g/dL ? Alanine transaminase (ALT) and AST =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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, superficial bladder tumors (Ta, Tis & T1). Any cancer curatively treated > 3 years prior to entry is permitted. • Renal failure requiring hemo- or peritoneal dialysis • History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) class 2; active coronary artery disease (CAD); cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin), or uncontrolled hypertension. Myocardial infarction more than 6 months prior to study entry is permitted. • Active clinically serious infections (> grade 2 National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [CTCAE] version 3.0) • Known history of human immunodeficiency virus (HIV) infection • Known Central Nervous System tumors including metastatic brain disease • Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry • History of organ allograft • Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results • Known or suspected allergy to the investigational agent or any agent given in association with this trial • Patients unable to swallow oral medications • Any condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study • Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to the start of study drug. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial. Excluded therapies and medications, previous and concomitant • Prior use of any systemic anti-cancer chemotherapy for HCC • Prior use of systemic investigational agents for HCC • Prior use of Raf-kinase inhibitors (RKI), VEGF inhibitors, MEK inhibitors or Farnesyl transferase inhibitors • Major surgery within 4 weeks of start of study drug • Radiotherapy during study or within 3 weeks prior to start of study drug. (Palliative radiotherapy will be allowed as described in Prior and Concomitant Therapy) • Use of biologic response modifiers, such as granulocyte colony-stimulating factor (G-CSF), within 3 weeks prior to study entry. (G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator; however they may not be substituted for a required dose reduction). Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 1 month prior to the study or during the study. • Autologous bone marrow transplant or stem cell rescue within four months of start of study drug • Concomitant treatment with rifampin and St John’s wort Extension with Crossover Phase The exclusion criterion required for this segment of the study is the following: •Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within seven days prior to enrolling in this portion of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Main objective: To evaluate safety, efficacy, PRO, and population PK of sorafenib versus placebo in patients with advanced HCC. Primary efficacy objectives: • Efficacy in patients treated with sorafenib will be compared to that in patients treated with placebo. • There are two primary efficacy objectives, which will be assessed independently. o Overall survival (OS) o Time to symptomatic progression (TTSP) If the analysis of either OS or TTSP (or both) is positive, the efficacy of sorafenib in HCC will be considered established. ;Secondary Objective: Secondary objectives: The secondary efficacy objectives are to assess the following variables between patients treated with sorafenib versus placebo: • Time to progression (TTP) • Overall disease control rate (Proportion of patients who have a best response rating of complete response [CR], PR or SD according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, that is maintained for at least 28 days from the first demonstration of that rating) • Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) response rate ;Primary end point(s): Primary efficacy variables • Overall Survival (OS) • Time to symptomatic progression (TTSP) Secondary efficacy variables • Time to progression (TTP) • Disease control rate • Patient Reported Outcomes (PRO) as measured by total score on FACT-Hep • Tertiary efficacy variables • Overall response rate • Overall response duration • Time to response • Patient Reported Outcomes (PRO) as measured by Physical and Functional Well-Being subscales of the FACT-Hep Other variables • Population PK parameters • Correlation between the following baseline characteristics (in order of priority) and key clinical endpoints (ie, response, TTP, TTSP, and OS): tumor pERK, phospho VEGF-R2 concentration, plasma proteomics, and gene expression profiling of blood cells and tumor biopsies | — |
Countries
Germany, Italy, Spain, United Kingdom
Outcome results
None listed