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A Study of Recombinant Vaccinia Virus to Evaluate the Safety and Efficacy of a Transdermal Injection Within the Tumor of Patients With Primary or Metastatic Hepatic Carcinoma

This study has been completed.
Sponsor:
Collaborator:
Green Cross Corporation
Information provided by:
Jennerex Biotherapeutics
ClinicalTrials.gov Identifier:
NCT00629759
First received: February 26, 2008
Last updated: January 3, 2013
Last verified: February 2008
  Purpose

The primary purpose of this study is to determine the maximum tolerable dose (MTD) and/or the maximum feasible dose (MFD), as well as to evaluate the safety of JX-594 (Pexa-Vec) injected within hepatic carcinoma tumors.


Condition Intervention Phase
Neoplasms, Liver
Genetic: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Clinical Study for Evaluating the Safety and Efficacy of a Transdermal Injection of JX-594 (Thymidine Kinase (-)/GM-CSF(+) Vaccinia Virus) Within the Tumor of Patients With Hepatic Carcinoma

Resource links provided by NLM:


Further study details as provided by Jennerex Biotherapeutics:

Primary Outcome Measures:
  • To determine the maximum tolerable dose (MTD) and/or the maximum feasible dose (MFD), as well as to evaluate the safety of JX-594 injected within unresectable solid tumor(s) within the liver [ Time Frame: Safety evaluation throughout study participation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Secondary objectives include determination of JX-594 pharmacokinetics, replication and shedding, immune response, and injection site tumor responses. [ Designated as safety issue: Yes ]

Enrollment: 14
Study Start Date: January 2006
Study Completion Date: August 2007
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
1e8 pfu (plaque forming units)total dose each treatment day
Genetic: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
The total dose is divided between 1-3 tumors located within the liver. Patients are treated with JX-594 once every 3 weeks until progression at the site(s) of injection or until the patient has received a maximum of 4 treatments.
Experimental: 2
3e8 pfu (plaque forming units) total dose each treatment day
Genetic: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
The total dose is divided between 1-3 tumors located within the liver. Patients are treated with JX-594 once every 3 weeks until progression at the site(s) of injection or until the patient has received a maximum of 4 treatments.
Experimental: 3
1e9 pfu (plaque forming units) total dose each treatment day
Genetic: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
The total dose is divided between 1-3 tumors located within the liver. Patients are treated with JX-594 once every 3 weeks until progression at the site(s) of injection or until the patient has received a maximum of 4 treatments.
Experimental: 4
3e9 pfu (plaque forming units) total dose each treatment day
Genetic: JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
The total dose is divided between 1-3 tumors located within the liver. Patients are treated with JX-594 once every 3 weeks until progression at the site(s) of injection or until the patient has received a maximum of 4 treatments.

Detailed Description:

Patients are treated with JX-594 once every three weeks until progression at the site(s) of injection or until the patient has received a maximum of 4 treatments; four additional cycles can be administered to patients with an objective response of the injected tumor(s) (i.e. 8 total treatments possible). Study dose levels are 1e8 pfu, 3e8 pfu, 1e9 pfu and 3e9 pfu per treatment. Standard Phase I dose-escalation guidelines are used, with 2-6 patients enrolled per cohort (3 if no dose-limiting toxicities are reported).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years
  • Patients with hepatic carcinoma (primary or metastatic) clinically or histologically confirmed to have tumors (≤10cm maximum diameter) that are progressing (refractory to standard treatment) despite regular treatment and that can be transdermally accessed by an injection needle in an imaging-guided procedure
  • Tumor progression despite undergoing regular treatment such as surgery, transarterial chemoembolization, chemotherapy, and radiotherapy
  • Performance score: Karnofsky Performance Score (KPS) ≥70
  • Expected survival of at least 16 weeks
  • For patients who are sexually active, able and willing to use contraceptives for a three month period during and after taking JX-594
  • WBC > 3,500 cells/mm3
  • ANC > 1,500 cells/mm3
  • Hemoglobin > 10g/dL
  • Platelet count > 75,000 plts/mm3
  • Serum creatinine < 1.5 mg/dL
  • AST, ALT < 2.5 x ULN
  • Total bilirubin ≤ 2.0 mg/dL
  • In patients with primary HCC, Child Pugh A or B
  • Able/willing to sign an IRB/IEC/REB-approved written consent form
  • Able and willing to comply with study procedures and follow-up examinations

Exclusion Criteria:

  • Pregnant or nursing an infant
  • Known infection with HIV
  • Clinically significant active infection or uncontrolled medical condition considered high risk for investigational new drug treatment
  • 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)
  • Patients with household contacts with significant immunodeficiency
  • History of exfoliative skin condition (e.g. severe eczema, ectopic dermatitis, or similar skin disorder) that at some stage has required systemic therapy
  • Severe or unstable cardiac disease
  • Use of adrenal cortical hormone drug or immunosuppressant within four weeks of study enrollment
  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: NCT00629759

Locations
Korea, Republic of
Dong-A University Hospital
Busan, Korea, Republic of, 602-715
Sponsors and Collaborators
Jennerex Biotherapeutics
Green Cross Corporation
Investigators
Study Director: David Kirn, MD Jennerex Biotherapeutics (Jennerex, Inc.)
  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: David Kirn, MD, President and CEO, Jennerex, Inc. (Jennerex Biotherapeutics)
ClinicalTrials.gov Identifier: NCT00629759     History of Changes
Other Study ID Numbers: JX594-IT-HEP001
Study First Received: February 26, 2008
Last Updated: January 3, 2013
Health Authority: South Korea: Korea Food and Drug Administration (KFDA)

Keywords provided by Jennerex Biotherapeutics:
Jennerex
unresectable liver tumors
primary liver cancer
metastatic liver cancer
oncolytic virus
vaccinia virus
Pexa-Vec

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Liver Neoplasms
Vaccinia
Adenocarcinoma
Carcinoma
DNA Virus Infections
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Poxviridae Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 24, 2014