Advanced Hepatocellular Carcinoma
Conditions
Interventions
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 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. Histologic or cytologic confirmed diagnosis of HCC. Advanced HCC disease not eligible for surgical and / or locoregional therapies progressive disease after surgical and / or locoregional therapies Child-Pugh Class A ECOG performance status 0-1 Life expectancy of at least 12 weeks Accessible for treatment and follow-up 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. 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. The lesion can be accurately measured uni-dimensionally according to RECIST criteria 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.) Bone metastases are not considered measurable lesions. Adequate hematologic function with absolute neutrophil counts >= 1,500/mm3, platelet count >= 60 x 109/L, and hemoglobin >= 8.5 g/dL Adequate hepatic function with serum total bilirubin = 2.8 g/dL and ALT and AST = 50% as measured by 2-D Echocardiogram 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 Men and women, ages 18 or older 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. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. Post menopause is defined as: Amenorrhea >= 12 consecutive months without another cause or For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, va
Exclusion criteria
Exclusion criteria: 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. Women who are pregnant or breastfeeding Women with a positive pregnancy test on enrollment or prior to investigational product administration. Sexually active fertile men not using effective birth control if their partners are WOCBP. Brain metastasis or evidence of leptomeningeal disease Known fibrolamellar HCC or mixed cholangiocarcinoma and HCC History of encephalopathy Ascites Evidence of portal hypertension with bleeding esophageal or gastric varices within the past 2 months Main portal vein* or vena cava thrombosis or occlusion. * Main portal vein is defined as the part of the portal vein between the inferior vena cava and the first bifurcation into the left and right vein. It is usually located in the porta hepatis. 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. History of active cardiac disease: Uncontrolled hypertension which defined as systolic blood pressure greater than 150 mmHg or diastolic pressure greater than 90 mmHg despite optimal medical management Congestive heart failure NYHA (New York Heart Association) class 3 and 4 Active coronary artery disease, unstable or newly diagnosed angina or myocardial infarction less than 12 months prior to study entry Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin Valvular heart disease >= CTCAE Grade 2 QTc (Fridericia) > 450 msec on two consecutive ECGs. (baseline ECG should be repeated if QTc is found to be > 450 msec) Thrombotic or embolic events within the past 6 months, such as a cerebrovascular accident (including transient ischemic attacks), pulmonary embolism Any other hemorrhage/bleeding event >= CTCAE Grade 3 within 4 weeks except for esophageal or gastric varices Active infection, less than 7 days after completing systemic antibiotic therapy Active, untreated hepatitis B Psychiatric illness/social situations that would limit compliance with study requirements History of non-healing wounds or ulcers, or bone fractures within 3 months of fracture 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 History of organ allograft or on an allograft waiting list Portal-caval shunts Inability to swallow tablets or untreated malabsorption syndrome Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication History of human immunodeficiency virus (HIV) infection Substance abuse, medical, psychological or social conditions that may interfere with the patient’s participation in the study or evaluation of the study results. Any medical condition that is unstable or which could jeopardize the safety of the patient and his/her compliance in the study. Positive pregnancy test Baseline serum sodium < 130 mmol/L Baseline serum potassium < 3.5 mmol/L (potassium supplementation may be given to restore the serum potassium above this level prior to study entry) Known or suspected history of allergy to brivanib
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival, computed for all per protocol subjects under non-inferiority test and all randomized subjects under superiority test, is defined as the time from randomization to death from any cause. Subjects who did not die will be censored on their last known alive date.;Primary endpoint of this study is overall survival. Subjects will be evaluated for tumor response every six weeks. Documentation of disease state will be performed by contrast enhanced computerized tomography (CT) or magnetic resonance imaging (MRI). Progression will be determined based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC. All randomized subjects will be followed for survival. An independent Data Monitoring Committee (DMC) will be instituted for the phase III HCC program of brivanib. The DMC will review the efficacy and safety data after 158 death events occur in this study. In addition, the Sponsor will independently review safety data in a blinded manner during the conduct of this trial to ensure that any safety issues are identified and addressed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to progression is defined as the time from randomization to disease progression. Subjects who never progress will be censored at their last tumor assessment date. For subjects with no tumor measurement, TTP will be censored at the date of randomization Objective response rate is defined as the proportion of randomized subjects in each treatment arm, whose best response is CR or PR using modified RECIST criteria as assessed by the investigators. Disease control rate is defined as the proportion of randomized subjects in each treatment arm, whose best response is CR, PR or SD using modified RECIST criteria as assessed by the investigators. Duration of response is defined as the time from randomization to disease progression or death for randomized subjects whose best response is PR or CR. Subjects who neither progress nor die will be censored on the date of their last tumor assessment. Duration of disease control is defined as the time from randomization to disease progression or death for randomized subjects whose best response is PR, CR or SD. Subjects who neither progress nor die will be censored on the date of their last tumor assessment. Time to response is defined as the time from randomization to the time when response criteria are met for CR or PR, whichever occurs first. Time to response is computed only for subjects whose best response is CR or PR.;Time to disease progression, investigator assessed objective response rate, disease control rate, duration of response, duration of disease control and time to response. | — |
Countries
Australia, Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Hong Kong, India, Italy, Japan, Korea, Democratic People's Republic of, Poland, Russian Federation, South Africa, Sweden, Taiwan, Province of China, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactJuliana Castro
Bristol-Myers Squibb
Outcome results
None listed