A Randomized, Double-blind, Multicenter Phase III Study of Brivanib versus Placebo as Adjuvant Therapy to Trans-Arterial Chemo-Embolization (TACE) in Patients withUnresectable Hepatocellular Carcinoma: The BRISK TA Study - The BRISK TA Study

Phase 1

• Conditions: intermediate stage hepatocellular carcinoma (HCC); MedDRA version: 9.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectable

• Registration Number: EUCTR2008-008715-26-FR
• Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04-16
• Last Update Posted: 1 October 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 1740

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 < 1.5 times the institutional upper limit of normal
d) Adequate renal function with serum creatinine = 2.0 mg/dL
e) Prothrombin time (PT): International normalized ratio (INR) < 1.7 or PT < 4 seconds above control
f) Left ventricular ejection fraction (LVEF) = 50% as measured by 2-D Electrocardiogram
g) All laboratory test finding should be stable within the range listed in a) - f)
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
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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified