Hepatocellular Carcinoma Study Comparing Vaccinia Virus Based Immunotherapy Plus Sorafenib vs Sorafenib Alone

Phase 3

Completed

Interventions: Biological: Pexastimogene Devacirepvec (Pexa Vec)
Drug: Sorafenib

Brief Summary: 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.

Detailed 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 459 patients were randomly assigned to 2 treatment arms- 234 patients in the Pexa-Vec followed by sorafenib treatment group and 225 patients in the sorafenib only treatment group.

Recruitment & Eligibility

Inclusion Criteria

Histological/cytological diagnosis of primary HCC
Advanced stage HCC (Barcelona Clinic Liver Cancer [BCLC] Stage C or B per American Association for the Study of Liver Disease [AASLD] guidelines)
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)
Child-Pugh Class A
Performance status 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
Adequate hematological, hepatic, and renal function:
Additional inclusion criteria exist

Exclusion Criteria

Histological diagnosis of cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma
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
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
History of moderate or severe ascites, bleeding esophageal varices, hepatic encephalopathy or pleural effusions related to liver insufficiency within 6 months of screening
Bulky disease patients - tumors encompassing >50% of the liver volume and / or inferior vena cava invasion
Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or immune-suppressive medication including high-dose corticosteroids
Ongoing severe inflammatory skin condition (as determined by the Investigator) requiring medical treatment
History of severe eczema (as determined by the Investigator) requiring medical treatment
Additional exclusion criteria exist

Arm && Interventions

Group	Intervention	Description
Pexa-Vec followed by Sorafenib	Pexastimogene Devacirepvec (Pexa Vec)	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.
Pexa-Vec followed by Sorafenib	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.
Sorafenib	Sorafenib	Sorafenib (400 mg twice daily) begins on Day 1.

Primary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	From date of randomization to the date of first documented radiographic tumor progression up to 53 months	Percentage of participants who showed overall response during their participation in the study. Per Modified Response Evaluation Criteria In Solid Tumors Criteria (mRECIST) and assessed by tri-phasic contrast enhanced CT: Complete Response (CR), Disappearance of intratumoral enhancing area; Partial Response (PR), \>=30% decrease in the sum of the diameters of enhancing area; Overall Response (OR) = CR + PR.

Secondary Outcome Measures

Name	Time	Method

Locations (142): University of Alabama
🇺🇸
Birmingham, Alabama, United States
Mayo Clinic Arizona
🇺🇸
Scottsdale, Arizona, United States
UC Irvine Medical Center
🇺🇸
Orange, California, United States
Stanford University School of Medicine
🇺🇸
Palo Alto, California, United States
University of Florida Shands Hospital
🇺🇸
Gainesville, Florida, United States
University of Chicago
🇺🇸
Chicago, Illinois, United States
University of Kansas Cancer Center
🇺🇸
Kansas City, Kansas, United States
University of Louisville
🇺🇸
Louisville, Kentucky, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Mercy Medical Center, Inc.
🇺🇸
Baltimore, Maryland, United States
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University of Alabama
🇺🇸Birmingham, Alabama, United States