Protocol No.: OCR14527
Sponsor Protocol No.: JX594-HEP024; JX594-HEP024
Protocol Title: Hepatocellular Carcinoma Study Comparing Vaccinia Virus Based Immunotherapy Plus Sorafenib vs Sorafenib Alone
Principal Investigator: Cabrera, Roniel
Objective: This is a randomized Phase 3 study to determine whether treatment with vaccinia virus based immunotherapy (Pexa-Vec) followed by sorafenib increases survival compared to treatment with sorafenib in patients with advanced hepatocellular carcinoma who have not received prior systemic therapy.
Description: This is a multi-center, randomized, open-label, Phase 3 study comparing Pexa Vec followed by sorafenib versus sorafenib in patients with advanced HCC without prior systemic therapy. A total of 600 patients will be randomly assigned to 2 treatment arms in a 1:1 ratio (300 in each arm) to reach at least 570 evaluable patients.
Phase: Phase III
Age Group: Adult
Age: 18 Years - N/A
Treatment: Experimental: Pexa-Vec followed by Sorafenib Pexa-Vec (pexastimogene devacirepvec) will be administered as 3 bi-weekly intratumoral (IT) injections of 1e9 pfu at day 1 and weeks 2 and 4, followed by sorafenib at Week 6. Active Comparator: Sorafenib Sorafenib (400 mg twice daily) begins on Day 1.
Detailed Eligibility: INCLUSION CRITERIA: 1. Ages 18 years old and older 2. Histological/cytological diagnosis of primary HCC 3. Advanced stage HCC (Barcelona Clinic Liver Cancer [BCLC] Stage C or B per American Association for the Study of Liver Disease [AASLD] guidelines) 4. At least one measurable viable tumor in the liver, ≥1 cm longest diameter (LD), using a dynamic imaging technique (arterial phase of triphasic computerized tomography [CT] scan, or dynamic contrast-enhanced magnetic resonance imaging [MRI]), and injectable under imaging-guidance (CT and/or ultrasound) 5. Child-Pugh Class A 6. Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale 7. Adequate hematological, hepatic, and renal function: 8. Additional inclusion criteria exist EXCLUSION CRITERIA: 1. Histological diagnosis of cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma 2. Symptomatic cardiovascular disease, including but not limited to significant coronary artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure within the preceding 12 months 3. Current or past history of cardiovascular disease (e.g.. past history of myocardial infarction, ischemic cardiomyopathy) unless cardiology consultation and clearance has been obtained for study participation 4 .History of moderate or severe ascites, bleeding esophageal varices, hepatic encephalopathy or pleural effusions related to liver insufficiency within 6 months of screening 5. Bulky disease patients - tumors encompassing >50% of the liver volume and / or inferior vena cava invasion 6. Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including high-dose corticosteroids 7. Ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment 8 History of severe eczema (as determined by the Investigator) requiring medical treatment 9. Additional exclusion criteria exist