A Study of Recombinant Vaccinia Virus Prior to Sorafenib to Treat Unresectable Primary Hepatocellular Carcinoma

• ClinicalTrials.gov Identifier: NCT01171651
• Recruitment Status: Completed
• First Posted: July 28, 2010
• Last Update Posted: January 20, 2016
• Sponsor: Jennerex Biotherapeutics
• Information provided by (Responsible Party): SillaJen, Inc. ( Jennerex Biotherapeutics )

Study Description

Brief Summary:

The purpose of this pilot safety study is to evaluate the safety and tolerability of JX-594 (Pexa-Vec) administered intravenously and intratumorally prior to standard sorafenib therapy.

Condition or disease	Intervention/treatment	Phase
Carcinoma, Hepatocellular	Drug: JX-594 followed by sorafenib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Open-Label Pilot Safety Study of JX-594 (Vaccinia GM-CSF/Thymidine Kinase-Deactivated Virus) Administered by IV Infusion Followed by Intratumoral Injection Prior to Standard Sorafenib Treatment in Patients With Unresectable Primary Hepatocellular Carcinoma
• Study Start Date: August 2009
• Actual Primary Completion Date: February 2013
• Actual Study Completion Date: December 2015

Arms and Interventions

Arm

Intervention/treatment

Experimental: JX-594 followed by sorafenib; 1e9 pfu (plaque-forming units) total JX-594 dose on each of up to four (4) JX-594 treatment days. Sorafenib is initiated after 3 JX-594 treatments and briefly interrupted if an optional 4th JX-594 treatment is given.

Drug: JX-594 followed by sorafenib; Patients will receive a total dose of 1e9 per treatment starting with one IV dose on Day 1 and injected intratumorally in 1-5 intrahepatic tumors on Day 8 and 22. Starting on Day 25 (3 days after the final JX-594 dose) patients will initiate oral sorafenib therapy twice daily according to standard approved guidelines. An optional maintenance JX-594 dose may be given intratumorally at Week 12 (sorafenib briefly interrupted).

Outcome Measures

Primary Outcome Measures :

1. Determine safety and tolerability of intravenous infusion of JX-594 followed by intratumoral injections with JX-594 prior to standard sorafenib therapy [ Time Frame: Safety evaluations through 28 days after last dose of JX-594 ]
   Adverse events will be collected and assessed to assess safety and tolerability through 28 days after last dose of JX-594 (or until all events considered probably or possibly related to JX-594 have resolved, stabilized, or returned to baseline status).

Secondary Outcome Measures :

1. Determine Disease Control Rate (DCR) at 12 weeks [ Time Frame: Disease control and response assessment at 12 weeks from first JX-594 dose ]
   DCR: confirmed complete response, partial response or stable disease based on modified RECIST and/or Choi response criteria
2. Determine radiographic response rate [ Time Frame: Periodically throughout study participation (average of up to 1 year) ]
   Response rate evaluation based on modified RECIST and/or Choi response criteria
3. Determine overall survival time [ Time Frame: Ongoing (average of 1 year) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Histological confirmation or clinical/laboratory diagnosis of primary hepatocellular carcinoma (HCC)
• Cancer is not surgically resectable for cure
• Child Pugh A or B
• Performance Score: KPS score of ≥ 70
• Platelet count ≥ 50,000 plts/mm3
• Total bilirubin ≤ 2.5 x ULN
• AST, ALT < 5.0 x ULN
• Acceptable coagulation status: INR ≤ 1.5 x ULN
• Acceptable kidney function: Serum creatinine < 2.0 mg/dL
• Sorafenib naive or refractory to sorafenib therapy Tumor Status: At least one intrahepatic tumor, and at least ≥50% of the total intrahepatic viable tumor mass, measurable by CT and injectable under imaging-guidance (note: injected and/or viable tumors must be previously untreated or ≥20% increase in size since preceding local-regional treatment).

Exclusion Criteria:

• Known contraindications to sorafenib
• Pregnant or nursing an infant
• Significant immunodeficiency due to underlying illness (e.g. hematological malignancies, congenital immunodeficiencies and/or HIV infection/AIDS) and/or medication (e.g. high-dose systemic corticosteroids)
• History of exfoliative skin condition (e.g. severe eczema, ectopic dermatitis, or similar skin disorder) that at some stage has required systemic therapy
• Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions
• Severe or unstable cardiac disease
• Current, known CNS malignancy
• Use of anti-platelet or anti-coagulation medication
• Use of the following anti-viral agents: ribavirin, adefovir, cidofovir (within 7 days prior to the first treatment), and PEG-IFN (within 14 days prior to the first treatment).
• Patients with household contacts who meet any of these criteria unless alternate living arrangements can be made during the patient's active dosing period and for 7 days following the last dose of study medication:
• Pregnant or nursing an infant
• Children < 12 months old
• History of exfoliative skin condition that at some stage has required systemic therapy
• Significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication

Contacts and Locations

Locations

Korea, Republic of

Pusan National University Hospital

Busan, Korea, Republic of

Pusan National University Yangsan Hospital

Yangsan, Korea, Republic of

Sponsors and Collaborators

Jennerex Biotherapeutics

Investigators

• Study Director: David H Kirn, MD; Jennerex Biotherapeutics

More Information

Additional Information:

Sponsor Company Website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Breitbach CJ, Arulanandam R, De Silva N, Thorne SH, Patt R, Daneshmand M, Moon A, Ilkow C, Burke J, Hwang TH, Heo J, Cho M, Chen H, Angarita FA, Addison C, McCart JA, Bell JC, Kirn DH. Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans. Cancer Res. 2013 Feb 15;73(4):1265-75. doi: 10.1158/0008-5472.CAN-12-2687. Epub 2013 Feb 7.

• Responsible Party: Jennerex Biotherapeutics
• ClinicalTrials.gov Identifier: NCT01171651
• Other Study ID Numbers: JX594-HEP016
• First Posted: July 28, 2010
• Last Update Posted: January 20, 2016
• Last Verified: June 2011

Keywords provided by SillaJen, Inc. ( Jennerex Biotherapeutics ):

Vaccinia; Vaccinia Virus; JX-594; Jennerex; Primary Hepatocellular Carcinoma; Primary Liver Cancer; Liver Cancer; Sorafenib; Nexavar; Pexa-Vec

Additional relevant MeSH terms:

Vaccinia; Carcinoma; Carcinoma, Hepatocellular; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Sorafenib; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action