A Study of the Effectiveness and Safety of AMG 386 and Sorafenib to Treat Advanced or Inoperable Hepatocellular Cancer
Phase 2
Completed
- Conditions
- Inoperable Hepatocellular CarcinomaAdvanced Hepatocellular Carcinoma
- Interventions
- Registration Number
- NCT00872014
- Lead Sponsor
- Amgen
- Brief Summary
The purpose of this study is to determine whether AMG 386, in combination with Sorafenib, is effective in the treatment of advanced or inoperable Hepatocellular cancer in subjects who have not received any prior systemic therapy except surgery or locoregional therapy.
Disease status and disease progression will be assessed every 8 weeks. Subjects will remain on treatment until: progressive disease by RECIST criteria; clinical progression; death or loss to follow-up; or withdrawal of informed consent.
- Detailed Description
The primary objective is to evaluate the efficacy of AMG 386 in combination with sorafenib as measured by the progression free survival (PFS) rate at 4 months in subjects with advanced or inoperable hepatocellular carcinoma (HCC).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
Inclusion Criteria
- Histologically confirmed advanced or inoperable HCC
- Child-Pugh A liver function score
- Measurable disease with at least one unidimensionally measurable lesion per RECIST 1.0 guidelines with modifications
- Adequate organ and hematological function
- Men or women greater than or equal to 18 years old
- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
Exclusion Criteria
- Subject is eligible for a liver transplant per investigators discretion
- Any previous systemic chemotherapy for HCC
- History of arterial or venous thromboembolism within 12 months prior to enrollment
- History of clinically significant bleeding within 6 months prior to enrollment
- History of central nervous system metastases
- Clinically significant cardiovascular disease within 12 months
- Uncontrolled hypertension
- Subjects with a history of prior malignancy
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 10 mg/kg cohort AMG 386 AMG 386 10mg/kg intravenously once weekly and Sorafenib 400mg orally twice daily in an every 4 weeks dosing schedule. 15mg/ kg cohort AMG 386 AMG 386 15mg/kg intravenously once weekly and Sorafenib 400mg orally twice daily in an every 4 weeks dosing schedule. 10 mg/kg cohort Sorafenib AMG 386 10mg/kg intravenously once weekly and Sorafenib 400mg orally twice daily in an every 4 weeks dosing schedule. 15mg/ kg cohort Sorafenib AMG 386 15mg/kg intravenously once weekly and Sorafenib 400mg orally twice daily in an every 4 weeks dosing schedule.
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) rate at 4 months 4 months
- Secondary Outcome Measures
Name Time Method Pharmacokinetic parameters for AMG 386 when used in combination with Sorafenib Weeks 1, 2, 5, 9, and every 16 weeks thereafter Incidence of adverse events and significant laboratory abnormalities Adverse events at every visit, significant laboratory abnormalities at least every 4 weeks Objective response rate, Disease control rate, Progression free survival, Overall survival, Time to progression Radiologic imaging every 8 weeks Pharmacokinetic parameter for Sorafenib when used in combination with AMG 386 Weeks 2, 5, 9, and every 16 weeks thereafter Incidence of the occurrence of anti-AMG 386 antibody formation Weeks 1, 5, 9, and every 16 weeks thereafter Baseline values of and changes from baseline in pharmacodynamic, immunologic, biochemical, transcriptional, pharmacogenetic and angiogenic markers Weeks 1, 2, 5, and every 16 weeks thereafter