Advanced Hepatocellular Carcinoma, Inoperable Hepatocellular Carcinoma
Conditions
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).
Interventions
DRUGAMG 386
Two doses of AMG 386 (15 mg/kg) IV QW will be studied
DRUGSorafenib
Sorafenib 400 mg PO BID orally twice daily in an every 4 week dosing schedule for 15mg/kg cohort & 10mg/kg cohort
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Progression free survival (PFS) rate at 4 months | 4 months |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic parameters for AMG 386 when used in combination with Sorafenib | Weeks 1, 2, 5, 9, and every 16 weeks thereafter |
| Pharmacokinetic parameter for Sorafenib when used in combination with AMG 386 | Weeks 2, 5, 9, and every 16 weeks thereafter |
| Objective response rate, Disease control rate, Progression free survival, Overall survival, Time to progression | Radiologic imaging every 8 weeks |
| 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 |
| Incidence of adverse events and significant laboratory abnormalities | Adverse events at every visit, significant laboratory abnormalities at least every 4 weeks |
Outcome results
None listed