Phase III, First Line Advanced Hepatocellular Carcinoma (HCC)

Phase 1

Conditions: advanced hepatocellular carcinoma
MedDRA version: 14.0Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2008-003533-24-BE

Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1800

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) Histologic or cytologic confirmed diagnosis of HCC prior to the start of investigational product administration.
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
h) At lease one measurable untreated lesion. All subjects must have at least one
previously un-treated, uni-dimensionally measurable lesion by MRI scan =
20mm or by spiral CT scan = 10mm.
i) The lesion can be accurately measured uni-dimensionally according to mRECIST for HCC 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, or albumin infusion etc.
4) Age and Sex
a) Men and women, ages 18 or older
b) Women of childbearing potential (WOCBP). WOCBP whose male partners receive study drug and male subjects 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.
In the case of urine pregnancy testing, a serum sample for pregnancy testing must
also be obtained within 72 hours prior to start of investigational product to
confirm the urine results. Investigational product may be initiated prior to the
confirmatory serum pregnancy test results being available.
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 up to 12 weeks after the last dose of investigational product 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) Any ascites that is considered clinically significant, defined as: i) Any ascites detected by physical exam at screening or ii) Any prior or current ascites that required treatment
e) Evidence of portal hypertension with bleeding esophageal or gastric varices
within the past 6 months
f) Main portal vein or vena cava occlusion caused by HCC.
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 (except HCC tumor thrombus) 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 8 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
j) Major surgical procedure, open biopsy, or significant traumatic injury less than 3
weeks prior to the start of investigational product administration 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