A Study of GC33 (RO5137382) in Patients With Advanced or Metastatic Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
This randomized, placebo-controlled, multicenter study will evaluate the efficacy and safety of GC33 (RO5137382) in previously treated patients with unresectable advanced or metastatic hepatocellular carcinoma. Participants will be stratified according to the level of GPC-3 expression in tumors and randomized to receive either GC33 (1600 mg intravenously) or placebo on Days 1 and 8 of Cycle 1 and every 2 weeks thereafter. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Official Title
-----------------
A Randomised, Placebo-controlled, Double-blind, Multicenter Phase II Trial of Intravenous GC33 at 1600 mg Q2W in Previously Treated Patients With Unresectable Advanced or Metastatic Hepatocellular Carcinoma (HCC)

Conditions
-----------------
Carcinoma, Hepatocellular

Intervention / Treatment
-----------------
* Drug: Placebo
* Drug: GC33


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult patients, >/= 18 years of age Histologically confirmed hepatocellular carcinoma (without fibro-lamellar subtype) Prior treatment with at least 1 systemic agent, with documented progressive disease after systemic agent(s), or documented adverse event(s) associated with prior systemic agent(s) that resulted in discontinuance of that (those) agent(s) Not a candidate for curative treatments (e.g. resection, transplantation) Child-Pugh A (score of 5-6) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate hematologic, hepatic and renal function Ability to provide, for central review, a tumor tissue sample to determine the level of GPC-3 expression by IHC Measurable disease by RECIST criteria Exclusion Criteria: Child Pugh B or C Known hepatocellular carcinoma with fibro-lamellar histology Known brain or leptomeningeal metastases Active infectious diseases requiring treatment except for hepatitis B and C History of organ allograft including liver transplant Anticipated or ongoing administration of anticancer therapies other than those administered in this study Anticancer treatment within 2 weeks prior to entering the study Patients who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies Patients receiving interferon therapy Pregnant or lactating women Known HIV positivity or AIDS-related illness History of significant hypersensitivity to similar agents (monoclonal antibody, protein-included drugs, Chinese hamster ovary products)

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* iv Days 1 and 8, and every 2 weeks thereafter<br>|
| Experimental: GC33 (RO5137382)<br> | Drug: GC33<br>* 1600 mg iv Day 1 and 8, and every 2 weeks thereafter<br>* Other names: RO5137382;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (tumor assessments according to RECIST criteria) |  | approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | approximately 32 months | 
| Time to progression (TTP): Time from randomization to first documented disease progression |  | approximately 24 months | 
| Disease control rate (DCR): Complete response, partial response or stable disease lasting at least 6 weeks |  | approximately 24 months | 
| Safety: Incidence of adverse events |  | approximately 24 months | 
| Pharmacokinetics: Serum concentrations (Cmax,Cmin) |  | Multiple sampling pre- and post-dose Days 1 and 8 Cycle 1, Day 1 Cycle 6, pre-dose Day 1 Cycles 2-11 | 
| GPC-3 expression in tumor tissue (biopsy) by immunohistochemistry (IHC) assay |  | at screening |