A Phase 2b Study of Modified Vaccinia Virus to Treat Patients Advanced Liver Cancer Who Failed Sorafenib

Study Overview
=================
Brief Summary
-----------------
This study is to determine whether JX-594 (Pexa-Vec) plus best supportive care is more effective in improving survival than best supportive care in patients with advanced Hepatocellular Carcinoma (HCC) who have failed sorafenib.

Official Title
-----------------
A Phase 2b Randomized Trial of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) Plus Best Supportive Care Versus Best Supportive Care in Patients With Advanced Hepatocellular Carcinoma Who Have Failed Sorafenib Treatment

Conditions
-----------------
Hepatocellular Carcinoma, Liver Cancer, HCC

Intervention / Treatment
-----------------
* Biological: JX-594 recombinant vaccina GM-CSF
* Other: Best Supportive Care


Participation Criteria
=================
Eligibility Criteria
-----------------
KEY Inclusion Criteria: Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC ECOG performance status 0, 1 or 2 Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites Hematocrit ≥30% or Hemoglobin ≥10 g/dL Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited >25% growth in viable tumor size since prior local-regional treatment. KEY Exclusion Criteria: Received sorafenib within 14 days prior to randomization Received systemic anti-cancer therapy other than sorafenib within 28 days of randomization Prior treatment with JX-594 Platelet count < 50,000 PLT/ mm3 Total white blood cell count < 2,000 cells/mm3 Prior or planned organ transplant Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication Severe or unstable cardiac disease Viable CNS malignancy associated with clinical symptoms Pregnant or nursing an infant History of inflammatory skin condition (e.g., eczema requiring previous treatment, atopic dermatitis)

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Patients on Arm A will receive 1 e9 pfu (plaque forming units) total dose of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) on each of six (6) treatments over 18 weeks. | Biological: JX-594 recombinant vaccina GM-CSF<br>* Patients will be randomised 2:1 to Arm A or Arm B and will receive 6 treatments on days 1, 8, 22, week 6, week 12, and week 18 plus best supportive care as needed.<br>|
| Other: Arm B<br>Patients on the control arm (Arm B) will have best supportive care over 18 weeks. | Other: Best Supportive Care<br>* Patients will be randomised 2:1 to Arm A or Arm B and will receive best supportive care as needed.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Determine overall survival for patients receiving JX-594 plus best supportive care (Arm A) compared with those patients receiving best supportive care (Arm B) in patients with advanced hepatocellular carcinoma (HCC) who have failed sorafenib treatment. | CT scan every six weeks until progression or death, assessed up to 21 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Tumor Progression | Determine time-to-tumor-progression (TTP) for Arm A compared with Arm B based on mRECIST for HCC. | CT scan every six weeks until progression or death, assessed up to 21 months | 
| Quality of Life | Determine the Quality of Life (QoL) of patients treated in Arm A compared with Arm B. | assessed up to 21 months (average) | 
| Tumor Response | Determine tumor response based on mRECIST for HCC of Arm A versus Arm B | CT scan every 6 weeks until progression or death, assessed up to 21 months (average) | 
| Safety profile of JX594 | Safety will be assessed by the number of adverse events (AEs) and serious adverse events (SAEs) | assessed up to 21 months (average) | 
| Time-to-symptomatic-progression | Determine time to progression of Arm A compared to Arm B. | assessed up to 21 months (average) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
advanced hcc, Jennerex, liver cancer, liver tumor, hepatocellular cancer, HCC, sorafenib, sorafenib failure, sorafenib intolerant, Nexavar, Nexavar failure, JX594, oncolytic virus, vaccinia, viral therapy, JX, Biotherapeutics, HEP018, traverse, biologic, Pexa-Vec