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 )

Tracking Information

• First Submitted Date: July 26, 2010
• First Posted Date: July 28, 2010
• Last Update Posted Date: January 20, 2016
• Study Start Date: August 2009
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 27, 2010)

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).

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 27, 2010)

• 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
• 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
• Determine overall survival time [ Time Frame: Ongoing (average of 1 year) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Recombinant Vaccinia Virus Prior to Sorafenib to Treat Unresectable Primary Hepatocellular Carcinoma
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Hepatocellular

Intervention

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).

Study Arms

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.

Intervention: Drug: JX-594 followed by sorafenib

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 1, 2013): 25
• Original Estimated Enrollment (submitted: July 27, 2010): 10
• Actual Study Completion Date: December 2015
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT01171651
• Other Study ID Numbers: JX594-HEP016
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: SillaJen, Inc. ( Jennerex Biotherapeutics )
• Study Sponsor: Jennerex Biotherapeutics
• Collaborators: Not Provided

Investigators

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

• PRS Account: SillaJen, Inc.
• Verification Date: June 2011