A Randomized, Double-blind, Multi-center Phase III Study of Brivanib plus BestSupportive Care (BSC) versus Placebo plus BSC in Subjects with AdvancedHepatocellular Carcinoma (HCC) who have Failed or are Intolerant to Sorafenib
- Conditions
- Advanced Hepatocellular CarcinomaC22.0C04.588.274.623
- Registration Number
- RBR-28gdtz
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- recruitment completed
- Sex
- Not specified
- Target Recruitment
- Not specified
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 hepatocellular carcinoma.
Advanced disease defined as:
Disease not eligible for surgical or loco-regional therapy or
Disease progressive after surgical or loco-regional therapy
Patient has failed >= 14 days of sorafenib treatment:
Documented radiographic progression Documented symptomatic progression
Documented intolerance to sorafenib Cirrhotic status of Child-Pugh Class A or B with a score of 7).
Eastern Cooperative Oncology Group performance status 0, 1, 2
Subjects who have a life expectancy of at least 8 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 selected as index lesions.
At lease one measurable untreated lesion. All subjects must have at least one
previously un-irradiated, bi-dimensionally measurable lesion by computerized tomography or magnetic resonance imaging scan >= 20mm. Index lesions that are previously un-irradiated and are bi-dimensionally measurable by spiral CT scan to be >= 10mm will be permitted.
The lesion can be accurately measured bidimensionally according to WHO
criteria.
The lesion has not been previously treated with surgery, radiation therapy,
radiofrequency ablation, percutaneous ethanol or acetic acid injection, or
cryoablation.
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 alanine aminotransferase and aspartate aminotransferase <= 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.
Male or female subjects >= 18 years of age.
Women of childbearing potential (WOCBP) must be using an adequate method
of contraception to avoid pregnancy throughout the study and 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 pot
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.
Any encephalopathy.
Any ascites.
Bleeding esophageal or gastric varices within 2 months prior to inclusion.
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 is defined as systolic blood pressure greater
than 150 mmHg or diastolic pressure greater than 90 mmHg despite optimal
medical management. Subjects with a history of persistent hypertension who
are receiving treatment with calcium channel blockers that are CYP3A4
substrates should be changed to an alternative antihypertensive medication.
Congestive heart failure NYHA (New York Heart Association) class III and
IV
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 >= Common Terminology Criteria for Adverse Events Grade 2.
QTc (Fridericia) > 450 msec on two consecutive electrocardiograms. (baseline electrocardiogram 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 > CTC AE Grade 3 within 4 weeks except
for esophageal or gastric varices
Active infection, less than 7 days after completing systemic antibiotic therapy.
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.
Vena cava thrombosis or occlusion.
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.
Active, untreated hepatitis B.
Positive pregnancy test.
Hyponatremia with 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 stu
Study & Design
- Study Type
- Intervention
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method