Neoplasms

All Conditions

Digestive System Diseases

Infections

Symptoms and General Pathology

Carcinoma

Carcinoma, Hepatocellular

Liver Neoplasms

Virus Diseases

Vaccinia

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Adenocarcinoma

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Liver Diseases

Communicable Diseases

Poxviridae Infections

DNA Virus Infections

Hematinics

All Drugs and Chemicals

Liver Extracts

1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart)

1e9 pfu (plaque-forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart)

Patients will be randomized 1:1 to one of two total doses (1e8 or 1e9 pfu)and injected intratumorally in 1-5 intrahepatic tumors on Days 1, 15, and 29.

JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF)

David Kirn, MD

Tony Reid, Md, PhD

Jeong Heo, MD, PhD

The purpose of this research study is to determine whether JX-594 (Pexa-Vec) has significant anti-tumoral activity and tolerability in primary hepatocellular carcinoma and to determine the dose to be used in further testing.

Hepatocellular carcinoma (HCC) is estimated to be the third most common cause of cancer-related deaths world-wide, and the fifth most common cancer diagnosis. According to the National Cancer Institute (NCI), approximately 17,000 new cases of HCC are diagnosed annually in the U.S. In Canada, the predicted incidence for 2007 is 1,350 new cases. In addition, approximately 10,000 new cases are diagnosed per year in S. Korea, 35,000 in the E.U. and 45,000 in Japan.

The five-year survival rate is estimated to be \<10% for all HCC patients. Given the poor prognosis of these patients there is a desperate need for new therapies.

Surgical resection and liver transplant are the only curative treatment for HCC. Small HCC tumor(s) (less than 3 cm in diameter) can be resected by hepatectomy, the most effective treatment. Surgery was associated with a reported 50-60% five-year survival rate, but unfortunately was possible in only 10-15% of cases. Liver transplant is considered for patients with tumors that are unresectable but that are still limited exclusively to the liver, have no extracapsular or vascular invasion within the liver, and for whom there are no medical contraindications to transplantation. Patients with unresectable HCC that cannot receive liver transplantation, and who do not require systemic therapy, may be administered percutaneous ethanol injection therapy (PEIT), radiofrequency ablation (RFA), transarterial chemoembolization (TACE), and/or radioembolization, depending on the size of the intrahepatic tumors and the underlying liver function.

HCC may be a good target for IT injection with JX-594 because of the relatively high rate of accessible tumors for injection, the positive response seen in a patient with HCC in a recently completed Phase I study of JX-594 intratumoral injection within the liver, excellent tumor responses in multiple preclinical cancer models, and the lack of effective, tolerable therapy for most patients with HCC who cannot receive curative surgery or immediate liver transplantation. Furthermore, it is speculated that JX-594 replication targets the EGFR pathway, and that it's spread within and between tumors is dependent upon the intratumoral vasculature; HCC has highly activated angiogenesis and EGFR pathways in the majority of cases.

A Study of Recombinant Vaccinia Virus to Treat Unresectable Primary Hepatocellular Carcinoma

A Phase II-a, Open-Label, Randomized Study of JX-594 (Thymidine Kinase-deleted Vaccinia Virus Plus GM-CSF) Administered by Intratumoral Injection in Patients With Unresectable Primary Hepatocellular Carcinoma

Proportion of subjects achieving disease control at 8 weeks based on a modified Response Evaluation Criteria in Solid Tumors v1.0 (mRECIST). Per mRECIST for target lesions as assessed by dynamic contrast enhanced dynamic MRI: Complete Response (CR), Disappearance of all tumor(s); Partial Response (PR), \>=30% decrease in the sum of longest diameter (LD) of tumor(s) taking as reference the baseline sum; Stable Disease (SD), any cases that do not qualify for PR or progressive disease (PD); PD, any increase of \>= 20% in the sum of longest diameter (LD) of tumor(s) taking as reference the baseline sum. Disease Control (DC) = CR or PR or SD. For mRECIST criteria, new tumor(s) that developed within the liver were measured (a new tumor was defined as a malignant tumor not present at baseline, was ≥ 1 cm in LD had typical hypervascular features of HCC). Their maximum diameter(s) were included in the sum of the maximum diameter; new tumors were not considered evidence for progression.

Treatment-related serious adverse events in patients treated at two dose levels

Number of subjects achieving disease control (non-progressive disease) at 8 weeks after treatment was initiated based on modified Response Evaluation Criteria in Solid Tumors for Hepatocellular Carcinoma (mRECIST for HCC). mRECIST for HCC adopted the concept of viable tumor as tumor tissue showing uptake in arterial phase of contrast enhanced radiologic imaging techniques. (see Lencioni and Llovet, Semin. Liver Dis. 2010; 30:52-60). Per mRECIST for HCC, for target lesions as assessed by contrast enhanced dynamic MRI: Complete Response (CR), Disappearance of any intratumoral arterial enhancement in all target (viable) lesions; Partial Response (PR), \>=30% decrease in the sum of diameters of viable target lesions; Stable Disease (SD), any cases that do not qualify for PR or progressive disease (PD); PD, any increase of \>= 20% in viable target lesions.

Disease Control (DC) = CR or PR or SD.

Jennerex Biotherapeutics

1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments.

Low Dose

1e9 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart). Each treatment dose was divided among 1-5 hepatic tumors; all tumors injected at day 1 were also injected at subsequent treatments.

High Dose

Total

Age, Continuous

Sex: Female, Male

United States

Canada

Korea, Republic of

Region of Enrollment

Manager, IP, Contracts, Translational Research

Patients having evaluable radiographic imaging, 2 patients in each arm were excluded due to unevaluable images, 1 patient in the low dose arm was excluded due to a protocol deviation

Proportion of Subjects Achieving Disease Control (Non-progressive Disease) at 8 Weeks After Initiation of Treatment

1e8 pfu (plaque forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart)

JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF): Patients will be randomized 1:1 to one of two total doses (1e8 or 1e9 pfu)and injected intratumorally in 1-5 intrahepatic tumors on Days 1, 15, and 29.

1e9 pfu (plaque-forming units) total dose of JX-594 (recombinant vaccinia virus) on each of three (3) treatment days (2 weeks apart)

JX-594: Recombinant vaccinia virus (TK-deletion plus GM-CSF): Patients will be randomized 1:1 to one of two total doses (1e8 or 1e9 pfu)and injected intratumorally in 1-5 intrahepatic tumors on Days 1, 15, and 29.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Recombinant Vaccinia Virus to Treat Unresectable Primary Hepatocellular Carcinoma	NCT00554372	Carcinoma, Hepa...	JX-594: Recombi...	18 Years -	SillaJen, Inc.
A Study of Recombinant Vaccinia Virus to Treat Unresectable Primary Hepatocellular Carcinoma	NCT00554372	Carcinoma, Hepa...	JX-594: Recombi...	18 Years -	SillaJen, Inc.
A Study of Recombinant Vaccinia Virus to Treat Unresectable Primary Hepatocellular Carcinoma	NCT00554372	Carcinoma, Hepa...	JX-594: Recombi...	18 Years -	SillaJen, Inc.

Spots Global Cancer Trial Database for unresectable primary hepatocellular carcinoma