A Phase 2a Study of Modified Vaccinia Virus to Treat Sorafenib-naïve Advanced Liver Cancer

Study Overview
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Brief Summary
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This study is to determine how effectively JX-594 (Pexa-Vec) will prolong life in patients with advanced Hepatocellular Carcinoma (HCC) who have not been previously treated with sorafenib, and the safe administration of JX-594 in five weekly IV infusions.

Detailed Description
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This was a Phase 2a, two-staged, single-arm, open-label study in sorafenib-naïve patients with advanced HCC. Patients received 5 weekly IV infusions of Pexa-Vec and could have continued to receive IV infusions of Pexa-Vec every 3 weeks until progressive disease (PD).

Official Title
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A Single-Arm, Open-Label Phase 2 Study of JX 594 (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) Administered by Weekly Intravenous (IV) Infusions in Sorafenib-naïve Patients With Advanced Hepatocellular Carcinoma (HCC)

Conditions
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Hepatocellular Carinoma

Intervention / Treatment
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* Biological: JX-594 recombinant vaccina GM-CSF


Participation Criteria
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Eligibility Criteria
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KEY Inclusion Criteria: Histologic or cytologic confirmation of advanced primary hepatocellular carcinoma (HCC) Measurable tumor (at least one tumor with ≥1 cm LD of contrast-enhancement during the arterial phase on CT scanning) ECOG performance status 0, 1 or 2 Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites Platelet count ≥50,000 plts/mm3 WBC count ≥2,000 cells/mm3 and ≤50,000 cells/mm3 Hemoglobin ≥10 g/dL Adequate liver function KEY Exclusion Criteria: Received sorafenib as previous treatment for HCC for more than 14 days History of severe exfoliative skin condition (e.g., eczema or atopic dermatitis requiring systemic therapy for > 4 weeks) Prior treatment with JX-594 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 Significant bleeding event within the last 12 months.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JX-594 recombinant vaccina GM-CSF<br>JX-594 recombinant vaccina GM-CSF | Biological: JX-594 recombinant vaccina GM-CSF<br>* Enrolled patients will receive 5 weekly IV infusions on Days 1, 8, 15, 22, and 29. After Day 43, if their disease has improved or remained stable and they have not started other cancer therapy, they may be able to continue to receive JX-594 via IV infusion every three weeks. This treatment extension may continue until radiologic progressive disease, initiation of other cancer therapy, or patient withdrawal.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Radiographic Response | Number of Participants with Complete response [CR] or partial response [PR] per modified Response Evaluation Criteria in Solid Tumors (mRECIST) for target and non-target lesions assessed by enhanced CT scan: CR, disappearance of intratumoral enhancing area; PR, >=30% decrease in sum of diameters of enhancing area; Radiographic Response = CR + PR | CT scans every 6 week from Week 6 up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TTP) | TTP (in months) was defined as the number of months from the date of first Pexa-Vec infusion to the date of disease progression. If the patient had no progression then TTP was censored at the date of last evaluable tumor assessment. TTP was summarized and a Kaplan Meier (KM) curve was constructed. | CT scans every 6 week from Week 6 up to 12 months. | 
| Overall Survival (OS) | OS was defined as the time from first dose of Pexa-Vec until death from any cause. For patients not known to have died at the time of the analysis, OS was censored on the date they were last known to be alive. OS was summarized and a KM curve was constructed. | CT scans every 6 week from Week 6 up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver Cancer, HCC, first line HCC, Pexa-Vec, JX-594