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

Primary Purpose

Carcinoma, Hepatocellular

Status

Completed

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

JX-594 followed by sorafenib

About this trial

This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Vaccinia, Vaccinia Virus, JX-594, Jennerex, Primary Hepatocellular Carcinoma, Primary Liver Cancer, Liver Cancer, Sorafenib, Nexavar, Pexa-Vec

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Pusan National University Hospital
Pusan National University Yangsan Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

JX-594 followed by sorafenib

Arm Description

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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

Determine radiographic response rate

Response rate evaluation based on modified RECIST and/or Choi response criteria

Determine overall survival time

Full Information

NCT ID

NCT01171651

First Posted

July 26, 2010

Last Updated

January 19, 2016

Sponsor

Jennerex Biotherapeutics

1. Study Identification

Unique Protocol Identification Number

NCT01171651

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

Study Type

Interventional

2. Study Status

Record Verification Date

June 2011

Overall Recruitment Status

Completed

Study Start Date

August 2009 (undefined)

Primary Completion Date

February 2013 (Actual)

Study Completion Date

December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Jennerex Biotherapeutics

4. Oversight

Data Monitoring Committee

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Carcinoma, Hepatocellular

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

JX-594 followed by sorafenib

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

JX-594 followed by sorafenib

Intervention Description

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).

Primary Outcome Measure Information:

Title

Determine safety and tolerability of intravenous infusion of JX-594 followed by intratumoral injections with JX-594 prior to standard sorafenib therapy

Description

Time Frame

Safety evaluations through 28 days after last dose of JX-594

Secondary Outcome Measure Information:

Title

Determine Disease Control Rate (DCR) at 12 weeks

Description

DCR: confirmed complete response, partial response or stable disease based on modified RECIST and/or Choi response criteria

Time Frame

Disease control and response assessment at 12 weeks from first JX-594 dose

Title

Determine radiographic response rate

Description

Response rate evaluation based on modified RECIST and/or Choi response criteria

Time Frame

Periodically throughout study participation (average of up to 1 year)

Title

Determine overall survival time

Time Frame

Ongoing (average of 1 year)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

David H Kirn, MD

Organizational Affiliation

Jennerex Biotherapeutics

Official's Role

Study Director

Facility Information:

Facility Name

Pusan National University Hospital

City

Busan

Country

Korea, Republic of

Facility Name

Pusan National University Yangsan Hospital

City

Yangsan

Country

Korea, Republic of

12. IPD Sharing Statement

Citations:

PubMed Identifier

23393196

Citation

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.

Results Reference

derived

Links:

URL

http://www.jennerex.com

Description

Sponsor Company Website

Learn more about this trial

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

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