A Study of the Effectiveness and Safety of AMG 386 and Sorafenib to Treat Advanced or Inoperable Hepatocellular Cancer

Study Overview
=================
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).

Official Title
-----------------
Phase 2 Open-label Multi-Center Study to Evaluate the Efficacy and Safety of AMG 386 and Sorafenib as First Line Therapy for Subjects With Advanced or Inoperable Hepatocellular Carcinoma

Conditions
-----------------
Advanced Hepatocellular Carcinoma, Inoperable Hepatocellular Carcinoma

Intervention / Treatment
-----------------
* Drug: AMG 386
* Drug: AMG 386
* Drug: Sorafenib


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 15mg/ kg cohort<br>AMG 386 15mg/kg intravenously once weekly and Sorafenib 400mg orally twice daily in an every 4 weeks dosing schedule. | Drug: AMG 386<br>* Two doses of AMG 386 (15 mg/kg) IV QW will be studied<br>Drug: Sorafenib<br>* Sorafenib 400 mg PO BID orally twice daily in an every 4 week dosing schedule for 15mg/kg cohort & 10mg/kg cohort<br>|
| Experimental: 10 mg/kg cohort<br>AMG 386 10mg/kg intravenously once weekly and Sorafenib 400mg orally twice daily in an every 4 weeks dosing schedule. | Drug: AMG 386<br>* Two doses of AMG 386 (10 mg/kg) IV QW will be studied<br>Drug: Sorafenib<br>* Sorafenib 400 mg PO BID orally twice daily in an every 4 week dosing schedule for 15mg/kg cohort & 10mg/kg cohort<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) rate at 4 months |  | 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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 | 
| 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 |