intermediate stage hepatocellular carcinoma (HCC) MedDRA version: 9.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable
Conditions
Interventions
Product Name: Brivanib Alaninate
Product Code: BMS-582664-02
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Brivanib Alaninate
CAS Number: 649735-63-7
Other descriptive name: VEGFR2
Conc
Sponsors
Bristol Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
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) Patients with diagnosis of hepatocellular carcinoma (HCC) meeting the criteria below: i) Biopsy-proven HCC (histology or cytology), OR ii) Radiological evidence of HCC showing lesion arterial hypervascularity and venous phase washout by either dynamic (triple-phase), contrast-enhanced computed tomography of the abdomen OR dynamic (triple-phase) contrast (gadolinium)-enhanced MRI, AND (1) Serology positive for hepatitis B or C, AND (2) Alpha fetoprotein > 400 µg/L at the time of diagnosis b) One lesion that is = 5 cm, OR multinodular disease with 4 or more lesions (at least one of which has a diameter > 3 cm) c) Cirrhotic status of Child-Pugh Class A or B with a score of 7 d) ECOG performance status of 0 or 1 e) Life expectancy of at least 12 weeks f) Ability to comply with visits/procedures required by protocol 3) Physical and Laboratory Test Findings 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 (ULN) c) Amylase and lipase =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) 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) Diffuse pattern of disease on CT/MRI b) Presence of extra-hepatic lesions c) Main portal vein or vena cava thrombosis or occlusion d) Intrahepatic or portal-caval shunts e) Any previous TACE procedure for HCC f) Prior use of systemic treatment for HCC g) Prior history of or current ascites or encephalopathy 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 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 III and IV 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) Hemorrhage/bleeding event = CTCAE Grade 3 within 4 weeks prior to study entry f) Prior history of gastrointestinal bleeding within the past year or presence of gastro-duodenal ulcers or gastro-esophageal varices documented by gastroscopy g) History of non-healing wounds or ulcers, or bone fractures within 3 months of fracture h) Major surgical procedure, open biopsy, or significant traumatic injury less than 3 weeks or those who receive minor surgical procedures (e.g., core biopsy or fine needle aspiration) within 1 week i) History of organ allograft or on an allograft waiting list j) Inability to swallow tablets or untreated malabsorption syndrome k) Pre-existing thyroid abnormality of thyroid function that cannot be maintained in the normal range with medication l) History of human immunodeficiency virus (HIV) infection m) Active infection, less than 7 days after completing systemic antibiotic therapy n) Active, untreated hepatitis o) Substance abuse, medical, psychological or social conditions that may interfere with the patient’s compliance with study requirements and participation in the study or evaluation of the study results. p) 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) Hyponatremia with 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) 5) Allergies an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the Overall Survival (OS) of HCC patients who receive brivanib as adjuvant treatments to TACE therapy, with the OS of HCC patients who receive matched placebo with TACE therapy.;Secondary Objective: • To compare the Time-To-Disease Progression (TTDP) of patients receiving brivanib with TACE therapy to that of patients receiving placebo with TACE therapy. • To compare the time to extrahepatic spread or vascular invasion in the brivanib and placebo arms. • To determine the total number of TACE sessions in the brivanib and placebo arms. • To compare the rate of TACE sessions in the brivanib and placebo arms. • To compare the Time-to-Progression (tumor) after the first TACE session in the brivanib and placebo arms. • To evaluate the safety of brivanib in combination with TACE.;Primary end point(s): The primary endpoint of the study is Overall Survival (OS). OS will be defined as the time from the date of randomization to the date of death. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive. | — |
Countries
France, Italy, Spain
Outcome results
None listed