A Randomized, Multi-Center, Blinded, Placebo-Controlled Study of Mapatumumab ([HGS1012], a Fully Human Monoclonal Antibody to TRAIL-R1) in Combination with Sorafenib as a First-Line Therapy in Subjects with Advanced Hepatocellular Carcinoma
- Conditions
- Advanced Hepatocellular CarcinomaMedDRA version: 14.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 100000004864
- Registration Number
- EUCTR2010-020798-17-DE
- Lead Sponsor
- Human Genome Sciences, Inc. (a wholly owned subsidiary of GlaxoSmithKline PLC)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
1. Child-Pugh Class A (see Appendix 1).
2. Barcelona Clinic Liver Cancer (BCLC) advanced stage (C) hepatocellular carcinoma, or BCLC intermediate stage (B) hepatocellular carcinoma if treatment with transarterial chemoembolization is not considered appropriate (see Appendix 2).
3. Measurable disease demonstrating intratumoral arterial enhancement by contrast enhanced computerized tomography (CT), with use of multislice scanners, or contrast enhanced dynamic magnetic resonance imaging (MRI), with at least 1 tumor lesion that meets the following criteria:
- Located in the liver.
- Can be accurately measured in at least 1 dimension.
- Well delineated area of viable, hypervascular (contrast enhancement in the arterial phase) tumor that is > 2 cm in the axial plane.
- Suitable for repeat measurement.
- Not previously treated with locoregional or systemic treatment unless the lesion shows a well-delineated area of viable (contrast enhancement in the arterial phase) tumor that is > 2 cm in the axial plane. (If the lesion is poorly demarcated or exhibits atypical enhancement as a result of the previous intervention, then it cannot be selected as a target lesion).
4. Radiologic eligibility (measurable disease) must be must be confirmed by the BICR prior to randomization.
5. Adequate bone marrow, renal and liver function:
- Absolute neutrophil count = 1.5 x 109 /L or = 1500 /mm3.
- Platelet count = 50 x 109 /L or = 50,000 /mm3.
- Hemoglobin = 9 g/dL (= 5.6 mmol/L) without growth factor support or transfusional support.
- Serum creatinine level = 2.0 mg/dL or = 176.8 µmol/L.
- Total bilirubin < 3.0 mg/dL or < 51.3 µmol/L.
- Aspartate transaminase (AST) and alanine transaminase (ALT) = 5.0 x upper limit of normal.
- Amylase and lipase = 1.5 x upper limit of normal.
- Serum albumin = 2.5 g/dL or = 25 g/L.
- International normalized ratio = 1.5.
6. Performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG) Scale (see Appendix 3).
7. Age 18 years or older.
8. Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study and follow-up procedures.
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
1. Any co-morbid condition that in the judgment of the investigator renders the subject at high risk of treatment complications or reduces the possibility of assessing clinical effect.
2. Received prior investigational or non-investigational cytotoxic chemotherapy, hormonal therapy, biological therapy (including but not limited to monoclonal antibodies, small molecules or other immunotherapy) to treat hepatocellular carcinoma.
3. Previously received mapatumumab or sorafenib.
4. Underwent resection, radiofrequency ablation, radiation or chemoembolization within 4 weeks before enrollment or not recovered from such treatments.
5. Need for concomitant anticancer therapy (surgery, radiation therapy, chemotherapy, immunotherapy, radiofrequency ablation) or other investigational agents during the study treatment period.
6. Major surgery (ie, the opening of a major body cavity, requiring the use of general anesthesia) within 4 weeks before enrollment; minor surgery (except for insertion of vascular access device) within 2 weeks before enrollment; or not yet recovered from the effects of the surgery.
7. Systemic steroids within 1 week before enrollment except steroids used as part of an antiemetic regimen or maintenance-dose steroids for non-cancerous disease.
8. Hepatic encephalopathy, per the investigator’s evaluation.
9. History of clinically significant gastrointestinal bleeding requiring procedural intervention (eg, variceal banding, transjugular intrahepatic portosystemic shunt procedure, arterial embolization, topical coagulation therapy) within 4 weeks before enrollment.
10. Gastrointestinal disease resulting in an inability to take oral medication or a requirement for intravenous hyperalimentation.
11. History of any infection requiring hospitalization or intravenous antibiotics within 2 weeks before enrollment.
12. Known brain or spinal cord metastases unless adequately treated (surgery or radiotherapy) with no evidence of progression and neurologically stable off anticonvulsants and steroids.
13. Known human immunodeficiency virus infection.
14. Unstable angina, myocardial infarction, cerebrovascular accident, = Class II congestive heart failure according to the New York Heart Association Classification for Congestive Heart Failure (see Appendix 4) within 6 months before enrollment.
15. Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin.
16. Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg despite optimal medical management).
17. Using and unable to discontinue use of concomitant strong CYP3A4 inducers (eg, including but not limited to St. John’s Wort, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital).
18. Pregnant female or nursing mother. All females with an intact uterus (unless amenorrheic for the 24 months before enrollment) must have a negative serum pregnancy test at screening. All non-sterile or non postmenopausal females must practice a medically accepted method of contraception over the course of the study and for 60 days after the last dose of study agent.
19. Males who do not agree to use effective contraception during the study and for a period of 60 days following the final dose of study agent.
20. Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s) or subject is receiving other investigational agents.
21. Acute or chronic severe
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: • To evaluate the efficacy of mapatumumab in combination with sorafenib in subjects with advanced hepatocellular carcinoma.<br><br>;Secondary Objective: • To evaluate the safety of the mapatumumab in combination with sorafenib in subjects with advanced hepatocellular carcinoma.<br>• To determine serum mapatumumab concentrations.<br>;Primary end point(s): • Time to progression (TTP)
- Secondary Outcome Measures
Name Time Method