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

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)

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.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carinoma
• Intervention / Treatment: Biological: JX-594 recombinant vaccina GM-CSF

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Pusan, Korea, Republic of
    • Pusan National University Hospital
  • Yangsan, Korea, Republic of
    • Pusan National University Yangsan Hospital
• Spain
  • Navarra
    • Pamplona, Navarra, Spain
      • University Clinic of Navarra
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: JX-594 recombinant vaccina GM-CSF

Biological: JX-594 recombinant vaccina GM-CSF; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Jennerex Biotherapeutics
• Investigators: Study Director: James Burke, MD, Jennerex Biotherapeutics

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): June 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: June 23, 2012
• First Submitted That Met QC Criteria: July 5, 2012
• First Posted (Estimate): July 10, 2012

Study Record Updates

• Last Update Posted (Actual): January 20, 2021
• Last Update Submitted That Met QC Criteria: December 29, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: HCC; Liver Cancer; JX-594; Pexa-Vec; first line HCC
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Poxviridae Infections; Vaccinia
• Other Study ID Numbers: JX594-IV-HEP021