A Randomized, Double-blind, Multi-center Phase III Study of Brivanib versus Sorafenib as First-line Treatment in Patients with Advanced Hepatocellular Carcinoma. - BRISK FL Study

Conditions: Hepatocellular carcinoma non-resectable
MedDRA version: 12.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectable

Registration Number: EUCTR2008-003533-24-IT

Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1800

Inclusion Criteria

1) Signed Written Informed Consent a) Voluntary signed and dated written informed consent form in accordance with regulatory and institutional guidelines obtained before the performance of any protocol-related procedures not part of normal patient care. 2) Target Population a) Histologic or cytologic confirmed diagnosis of HCC. b) Advanced HCC i) disease not eligible for surgical and / or locoregional therapies ii) progressive disease after surgical and / or locoregional therapies c) Child-Pugh Class A d) ECOG performance status 0-1 Life expectancy of at least 12 weeks f) Accessible for treatment and follow-up g) Locoregional therapy must be completed at least 3 weeks prior to the baseline scan; previously treated lesions are not to be selected as target lesions. h) At lease one measurable untreated lesion. All subjects must have at least one previously un-treated, uni-dimensionally measurable lesion by CT or MRI scan ≥ 20mm. Target lesions that are previously un-treated and are uni-dimensionally measurable by spiral CT scan to be≥ 10mm will be permitted. i) The lesion can be accurately measured uni-dimensionally according to RECIST criteria ii) The lesion has not been previously treated with surgery, radiotherapy, and /or locoregional therapy (eg: radiofrequency ablation (RFA), percutaneous ethanol or acetic acid injection (PEI / PAI), transcatheter arterial chemoembolization (TACE) or cryoablation, etc.) iii) Bone metastases are not considered measurable lesions. 3) Physical and Laboratory Test Finding a) Adequate hematologic function with absolute neutrophil counts ≥ 1,500/mm3, platelet count ≥ 60 x 10E9/L, and hemoglobin ≥ 8.5 g/dL b) Adequate hepatic function with serum total bilirubin ≤ 3 mg/dL, serum albumin ≥ 2.8 g/dL and ALT and AST ≤ 5 times the institutional upper limits of normal c) Amylase and lipase ≤ 1.5 times the institutional upper limit of normal d) Adequate renal function with serum creatinine ≤ 2.0 mg/dL e) International normalized ratio (INR) ≤ 2.3 or Prothrombin time (PT) ≤ 6 seconds above control f) Left ventricular ejection fraction (LVEF) ≥ 50% as measured by 2-D Echocardiogram g) All laboratory test finding should be stable within the range listed in 3a) - 3f) without continuous supportive treatment, such as blood transfusion, coagulation factors and / or platelet infusion, red / white blood cell growth factor administration, albumin infusion, ursodeoxycholic acid, or drug treatment for lowering liver enzyme / bilirubin, etc. 4) Age and Sex a) Men and women, ages 18 or older b) Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the last dose of investigational product in such a manner that the risk of pregnancy is minimized.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of investigational product. b) Women who are pregnant or breastfeeding c) Women with a positive pregnancy test on enrollment or prior to investigational product administration. d) Sexually active fertile men not using effective birth control if their partners are WOCBP. 2) Target Disease Exceptions a) Brain metastasis or evidence of leptomeningeal disease b) Known fibrolamellar HCC or mixed cholangiocarcinoma and HCC c) History of encephalopathy d) Ascites e) Evidence of portal hypertension with bleeding esophageal or gastric varices within the past 2 months f) Main portal vein or vena cava thrombosis or occlusion. 3) Medical History and Concurrent Diseases a) 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 > 5 years prior to entry is permitted. b) History of active cardiac disease: i) Uncontrolled hypertension which defined as systolic blood pressure greater than 150 mmHg or diastolic pressure greater than 90 mmHg despite optimal medical management ii) Congestive heart failure NYHA (New York Heart Association) class 3 and 4 iii) Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction less than 12 months prior to study entry. iv) Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin v) Valvular heart disease ≥ CTCAE Grade 2 c) QTc (Fridericia) > 450 msec on two consecutive ECGs. (baseline ECG should be repeated if QTc is found to be > 450 msec) d) Thrombotic or embolic events within the past 6 months, such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism e) Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks except for esophageal or gastric varices f) Active infection, less than 7 days after completing systemic antibiotic therapy g) Active, untreated hepatitis B h) Psychiatric illness/social situations that would limit compliance with study requirements i) History of non-healing wounds or ulcers, or bone fractures within 3 months of fracture j) Major surgical procedure, open biopsy, or significant traumatic injury less than 3 weeks or those who receive minor surgical procedures (eg core biopsy or fine needle aspiration) within 1 week k) History of organ allograft or on an allograft waiting list l) Portal-caval shunts m) Inability to swallow tablets or untreated malabsorption syndrome n) Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication o) History of human immunodeficiency virus (HIV) infection p) Substance abuse, medical, psychological or social conditions that may interfere with the patient?s participation in the study or evaluation of the study results. q) Any medical condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study. 4) Physical and Laboratory Test Findings a) Positive pregnancy test b) Baseline serum sodium < 130 mmol/L c) Baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to study entry)FOR A COMPLETE LIST SEE PAPER COP

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the Overall Survival (OS) of brivanib versus sorafenib in subjects with advanced HCC who have not received prior systemic treatment.;Secondary Objective: To compare the time to progression (TTP) (investigator assessed using modified RECIST criteria) To compare the investigator assessed objective response rate (ORR) and disease control rate (DCR) using modified RECIST criteria To determine duration of response, duration of disease control, and time to response (TTR) To assess the safety profile of brivanib and sorafenib To explore PK and exposure-response in the study population To compare time to symptomatic progression To compare health-related quality of life.;Primary end point(s): Primary endpoint of this study is overall survival.

Secondary Outcome Measures