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

Neoplasms, Liver Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00629759
• Other study ID #: JX594-IT-HEP001
• Status: Completed
• Phase: Phase 1
• First received: February 26, 2008
• Last updated: January 3, 2013
• Start date: January 2006
• Est. completion date: August 2007

Study information

• Verified date: February 2008
• Source: Jennerex Biotherapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Korea: Korea Food and Drug Administration (KFDA)
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: August 2007
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Hepatocellular
• Liver Neoplasms
• Neoplasms, Liver
• Vaccinia

Intervention

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.

Locations

Country	Name	City	State
Korea, Republic of	Dong-A University Hospital	Busan

Sponsors (2)

Lead Sponsor	Collaborator
Jennerex Biotherapeutics	Green Cross Corporation

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Safety evaluation throughout study participation	Yes
Secondary	Secondary objectives include determination of JX-594 pharmacokinetics, replication and shedding, immune response, and injection site tumor responses.			Yes

External Links

•   Sponsor company website