Clinical trial NCT01171651: A Study of Recombinant Vaccinia Virus Prior to Sorafenib to Treat Unresectable Primary Hepatocellular Carcinoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Keywords: Vaccinia
Vaccinia Virus
JX-594
Jennerex
Primary Hepatocellular Carcinoma
Primary Liver Cancer
Liver Cancer
Sorafenib
Nexavar
Pexa-Vec
Lead sponsor: SillaJen, Inc.
Sponsor class: INDUSTRY
First posted: 2010-07-28
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Determine safety and tolerability of intravenous infusion of JX-594 followed by intratumoral injections with JX-594 prior to standard sorafenib therapy
timeFrame: Safety evaluations through 28 days after last dose of JX-594
Secondary outcomes:
measure: Determine Disease Control Rate (DCR) at 12 weeks
timeFrame: Disease control and response assessment at 12 weeks from first JX-594 dose
measure: Determine radiographic response rate
timeFrame: Periodically throughout study participation (average of up to 1 year)
measure: Determine overall survival time
timeFrame: Ongoing (average of 1 year)
Other outcomes:
Locations:
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
Study officials:
affiliation: Jennerex Biotherapeutics
name: David H Kirn, MD
role: STUDY_DIRECTOR
References:
citation: Breitbach CJ, Arulanandam R, De Silva N, Thorne SH, Patt R, Daneshmand M, Moon A, Ilkow C, Burke J, Hwang TH, Heo J, Cho M, Chen H, Angarita FA, Addison C, McCart JA, Bell JC, Kirn DH. Oncolytic vaccinia virus disrupts tumor-associated vasculature in humans. Cancer Res. 2013 Feb 15;73(4):1265-75. doi: 10.1158/0008-5472.CAN-12-2687. Epub 2013 Feb 7.