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

Carcinoma, Hepatocellular Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01171651
• Other study ID #: JX594-HEP016
• Status: Completed
• Phase: Phase 2
• First received: July 26, 2010
• Last updated: January 19, 2016
• Start date: August 2009
• Est. completion date: December 2015

Study information

• Verified date: June 2011
• Source: SillaJen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: December 2015
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Vaccinia

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).

Locations

Country	Name	City	State
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan

Sponsors (1)

Lead Sponsor	Collaborator
Jennerex Biotherapeutics

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine safety and tolerability of intravenous infusion of JX-594 followed by intratumoral injections with JX-594 prior to standard sorafenib therapy	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).	Safety evaluations through 28 days after last dose of JX-594	Yes
Secondary	Determine Disease Control Rate (DCR) at 12 weeks	DCR: confirmed complete response, partial response or stable disease based on modified RECIST and/or Choi response criteria	Disease control and response assessment at 12 weeks from first JX-594 dose	No
Secondary	Determine radiographic response rate	Response rate evaluation based on modified RECIST and/or Choi response criteria	Periodically throughout study participation (average of up to 1 year)	No
Secondary	Determine overall survival time		Ongoing (average of 1 year)	No

External Links

•   Sponsor Company Website