Neoplasms, Liver
Conditions
Keywords
Jennerex, unresectable liver tumors, primary liver cancer, metastatic liver cancer, oncolytic virus, vaccinia virus, Pexa-Vec
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).
Interventions
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.
Sponsors
Jennerex Biotherapeutics
Green Cross Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objectives include determination of JX-594 pharmacokinetics, replication and shedding, immune response, and injection site tumor responses. | Throughout the study participation, up to 1 year post-treatment |
Countries
South Korea
Contacts
STUDY_DIRECTORDavid Kirn, MD
Jennerex Biotherapeutics (Jennerex, Inc.)
Outcome results
None listed