| 5 | |
| RBR-84sdd6 | |
| A Randomized, Double-blind, Multi-center Phase III Study of Brivanib versus Sorafenib as First-line Treatment in Patients with Advanced Hepatocellular Carcinoma | |
| A Randomized, Double-blind, Multi-center Phase III Study of Brivanib versus Sorafenib as First-line Treatment in Patients with Advanced Hepatocellular Carcinoma | |
| None | |
| recruiting | |
| Intervention | |
| 3, randomized-controlled, double-blind | |
| 3 | |
| None | |
| None | |
| None | |
| 2011-06-27 | |
| 2010-05-01 | |
| None | |
| None | |
| https://ensaiosclinicos.gov.br/rg/RBR-84sdd6 | |
| None | |
| 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 <= 3 mg/dL, serum albumin
>= 2.8 g/dL and ALT and AST <= 5 times the institutional upper limits of normal
Amylase and lipase <= 1.5 times the institutional upper limit of normal
Adequate renal function with serum creatinine <= 2.0 mg/dL
International normalized ratio (INR) <= 2.3 or Prothrombin time (PT) <= 6 seconds
above control
Left ventricular ejection fraction (LVEF) >= 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, vasectomy) should be considered to be of childbearing
potential.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product. | |
| 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 or sorafenib or any agents
given in association with this trial
Prior use of any systemic anti-cancer chemotherapy, immunotherapy or molecular
targeted agents for HCC
Concomitant treatment with rifampin (and its analogues), or St John’s wort
Prior use of systemic investigational agents for HCC
Radiotherapy within 4 weeks prior to start of study drug
Required anticoagulation therapy with an agent such as coumadin, warfarin or
heparin
Required chronic anti-platelet therapy (aspirin at dose >= 300 mg/day, clopidogrel
at dose >= 75 mg/day)
Prisoners or subjects who are involuntarily incarcerated
Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (eg, infectious disease) illness. | |
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| None | |
| None | |
| None | |
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| 2026-05-11 05:16:35 | |