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

NCT01171651 | Completed Phase 2

• 1 other identifier: JX594-HEP016
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

Carcinoma, Hepatocellular

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (3)

• Determine Disease Control Rate (DCR) at 12 weeks

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

• Determine radiographic response rate

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

• Determine overall survival time

  Ongoing (average of 1 year)

Study Arms (1)

JX-594 followed by sorafenib

EXPERIMENTAL

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

Interventions

JX-594 followed by sorafenib DRUG

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).

JX-594 followed by sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Jennerex Biotherapeutics: lead

Study Sites (2)

Pusan National University Hospital

Busan, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, South Korea

Location

Related Publications (1)

• 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.

  PMID: 23393196 DERIVED

Related Links

• Sponsor Company Website

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Vaccinia; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Poxviridae Infections; DNA Virus Infections; Virus Diseases; Infections

Study Officials

• David H Kirn, MD

  Jennerex Biotherapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 26, 2010
• First Posted: July 28, 2010
• Study Start: August 1, 2009
• Primary Completion: February 1, 2013
• Study Completion: December 1, 2015
• Last Updated: January 20, 2016

Record last verified: 2011-06

Locations

KR (2)