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
Primary Purpose
Neoplasms, Liver
Status
Completed
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
Sponsored by
About this trial
This is an interventional treatment trial for Neoplasms, Liver focused on measuring Jennerex, unresectable liver tumors, primary liver cancer, metastatic liver cancer, oncolytic virus, vaccinia virus, Pexa-Vec
Eligibility 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
Sites / Locations
- Dong-A University Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
1
2
3
4
Arm Description
1e8 pfu (plaque forming units)total dose each treatment day
3e8 pfu (plaque forming units) total dose each treatment day
1e9 pfu (plaque forming units) total dose each treatment day
3e9 pfu (plaque forming units) total dose each treatment day
Outcomes
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
Secondary Outcome Measures
Secondary objectives include determination of JX-594 pharmacokinetics, replication and shedding, immune response, and injection site tumor responses.
Full Information
NCT ID
NCT00629759
First Posted
February 26, 2008
Last Updated
January 3, 2013
Sponsor
Jennerex Biotherapeutics
Collaborators
Green Cross Corporation
1. Study Identification
Unique Protocol Identification Number
NCT00629759
Brief Title
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
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2008
Overall Recruitment Status
Completed
Study Start Date
January 2006 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
August 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Jennerex Biotherapeutics
Collaborators
Green Cross Corporation
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neoplasms, Liver
Keywords
Jennerex, unresectable liver tumors, primary liver cancer, metastatic liver cancer, oncolytic virus, vaccinia virus, Pexa-Vec
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
1e8 pfu (plaque forming units)total dose each treatment day
Arm Title
2
Arm Type
Experimental
Arm Description
3e8 pfu (plaque forming units) total dose each treatment day
Arm Title
3
Arm Type
Experimental
Arm Description
1e9 pfu (plaque forming units) total dose each treatment day
Arm Title
4
Arm Type
Experimental
Arm Description
3e9 pfu (plaque forming units) total dose each treatment day
Intervention Type
Genetic
Intervention Name(s)
JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Secondary objectives include determination of JX-594 pharmacokinetics, replication and shedding, immune response, and injection site tumor responses.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Kirn, MD
Organizational Affiliation
Jennerex Biotherapeutics (Jennerex, Inc.)
Official's Role
Study Director
Facility Information:
Facility Name
Dong-A University Hospital
City
Busan
ZIP/Postal Code
602-715
Country
Korea, Republic of
12. IPD Sharing Statement
Citations:
PubMed Identifier
18495536
Citation
Park BH, Hwang T, Liu TC, Sze DY, Kim JS, Kwon HC, Oh SY, Han SY, Yoon JH, Hong SH, Moon A, Speth K, Park C, Ahn YJ, Daneshmand M, Rhee BG, Pinedo HM, Bell JC, Kirn DH. Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol. 2008 Jun;9(6):533-42. doi: 10.1016/S1470-2045(08)70107-4. Epub 2008 May 19. Erratum In: Lancet Oncol. 2008 Jul;9(7):613.
Results Reference
derived
Links:
URL
http://www.jennerex.com
Description
Sponsor company website
Learn more about this trial
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
We'll reach out to this number within 24 hrs