A Randomized, Double-blind, Multi-center Phase III Study of Brivanib versus Sorafenibas First-line Treatment in Patients with Advanced Hepatocellular Carcinoma (The BRISK FL Study)Pharmacogenetics Blood Sample Amendment 1 (v1.0, dated 10-Dec-2008) //////////Estudio fase III aleatorizado, doble ciego, multicéntrico, de brivanib frente a sorafenib como tratamiento de primera línea en pacientes con carcinoma hepatocelular avanzado (Estudio BRISK FL)Enmienda sobre muestras de sangre para farmacogenética Número 01 ((v1.0, de fecha 10-Dic-2008) - BRISK FL Study
- Conditions
- advanced hepatocellular carcinoma ///////////Carcinoma Hepatocelular avanzadoMedDRA version: 9.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectable
- Registration Number
- EUCTR2008-003533-24-ES
- Lead Sponsor
- Bristol Myers Squibb International Corporation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1665
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
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) 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)
5) Allergies and Adverse Drug Reactions
a) Known or sus
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method