Advanced Hepatocellular Carcinoma
Conditions
Interventions
Sponsors
Bristol-Myers Squibb
Eligibility
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 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 = 2.8 g/dL and alanine aminotransferase and aspartate aminotransferase = 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
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoint of this study is overall survival in the intent-to-treat population. Subjects will be evaluated for tumor response every six weeks. Documentation of disease state will be performed by either computerized tomography (CT) or magnetic resonance imaging (MRI). Progression will be determined based on modified World Health Organization (WHO) criteria. All randomized subjects will be followed for survival. | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to progression (TTP): Time from randomization to disease progression. Subjects who never progress will be censored at their last tumor assessment date. For subjects with no tumor measurements, TTP will be censored at the date of randomization. Objective response rate (ORR): Proportion of randomized subjects in each treatment arm, whose best response is CR or PR using modified WHO criteria as assessed by the investigators. Disease control rate: Proportion of randomized subjects in each treatment arm, whose best response is CR, PR or SD using modified WHO criteria as assessed by the investigators. Time to response: Time from randomization to the time when response criteria are met for CR or PR, whichever occurs first. Time to response is computed only for subjects whose best response is CR or PR. Duration of response: Time from randomization to disease progression or death for randomized subjects whose best response is PR or CR. Subjects who neither progress nor die will be censored on the date of their last tumor assessment. Duration of disease control: Time for randomization to disease progression or death from randomized subjects whose best response is PR, CR or SD. Subjects who neither progress nor die will be censored on the date of their last tumor assessment. | — |
Countries
Belgium, Brazil, Canada, China, France, Germany, Greece, Hong Kong, India, Italy, Japan, Korea, Democratic People's Republic of, Russian Federation, Sweden, Taiwan, Province of China, United States
Contacts
Public ContactJuliana Castro
Bristol-Myers Squibb
Outcome results
None listed