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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Jennerex Biotherapeutics.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Jennerex Biotherapeutics
ClinicalTrials.gov Identifier:
NCT01171651
First received: July 26, 2010
Last updated: January 13, 2014
Last verified: June 2011
  Purpose

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 Intervention Phase
Carcinoma, Hepatocellular
Drug: JX-594 followed by sorafenib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Jennerex Biotherapeutics:

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 [ Time Frame: Safety evaluations through 28 days after last dose of JX-594 ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Disease control and response assessment at 12 weeks from first JX-594 dose ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    Response rate evaluation based on modified RECIST and/or Choi response criteria

  • Determine overall survival time [ Time Frame: Ongoing (average of 1 year) ] [ Designated as safety issue: No ]

Enrollment: 25
Study Start Date: August 2009
Estimated Study Completion Date: June 2014
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01171651

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:
No publications provided by Jennerex Biotherapeutics

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jennerex Biotherapeutics
ClinicalTrials.gov Identifier: NCT01171651     History of Changes
Other Study ID Numbers: JX594-HEP016
Study First Received: July 26, 2010
Last Updated: January 13, 2014
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)
United States: Food and Drug Administration

Keywords provided by Jennerex Biotherapeutics:
Vaccinia
Vaccinia Virus
JX-594
Jennerex
Primary Hepatocellular Carcinoma
Primary Liver Cancer
Liver Cancer
Sorafenib
Nexavar
Pexa-Vec

Additional relevant MeSH terms:
Carcinoma
Vaccinia
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Poxviridae Infections
DNA Virus Infections
Virus Diseases
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014