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

Hepatocellular Carcinoma (HCC) Clinical Trial

— PHOCUS  

Official title:

A Phase 3 Randomized, Open-Label Study Comparing Pexa Vec (Vaccinia GM CSF / Thymidine Kinase-Deactivated Virus) Followed by Sorafenib Versus Sorafenib in Patients With Advanced Hepatocellular Carcinoma (HCC) Without Prior Systemic Therapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02562755
• Other study ID #: JX594-HEP024
• Status: Completed
• Phase: Phase 3
• Start date: October 2015
• Est. completion date: July 2020

Study information

• Verified date: December 2020
• Source: SillaJen, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 459
• Est. completion date: July 2020
• Est. primary completion date: July 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma (HCC)
• Vaccinia

Intervention

Biological:
• Pexastimogene Devacirepvec (Pexa Vec)
Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells.

Drug:
• Sorafenib
Sorafenib belongs to the pharmacotherapeutic group of antineoplastic agents, protein kinase inhibitors, ATC code: L01XE05. Sorafenib is a multi-kinase inhibitor which has demonstrated both anti-proliferative and anti-angiogenic properties in vitro and in vivo. Sorafenib is approved for the treatment of advanced HCC and is the Standard Of Care for this disease.

Locations

Country	Name	City	State
Australia	Site No. 8409	Adelaide
Australia	Site No. 8412	Adelaide
Australia	Site No. 8403	Brisbane
Australia	Site No. 8401	Camperdown
Australia	Site No. 8407	Clayton
Australia	Site No. 8406	Concord
Australia	Site No. 8408	Fitzroy
Australia	Site No. 8405	Footscray
Australia	Site No. 8414	Heidelberg
Australia	Site No. 8411	Melbourne
Australia	Site No. 8402	Parkville
Australia	Site No. 8415	Perth
Australia	Site No. 8413	Sydney
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Juravinski Cancer Centre	Hamilton	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario
China	Site 8829	Changchun
China	Site No. 8821	Changsha
China	Site 8811	Fuzhou
China	Site 8820	Fuzhou
China	Site No.8816	Guangdong
China	Site 8827	Guangzhou
China	Site No.8828	Guangzhou
China	Site 8832	Hangzhou
China	Site No. 8802	Harbin
China	Site 8805	Hefei
China	Site No. 8808	Hefei
China	Site No.8815	Hefei
China	Site No. 8801	Nanjing
China	Site 8833	Qingdao
China	Site 8806	Shanghai
China	Site 8822	Shanghai
China	Site 8831	Shanghai
China	Site No. 8823	Xi'an
China	Site No. 8825	Xi'an
France	Site No. 9013	Bondy
France	Site No. 9005	Bordeaux
France	Site No. 9003	Créteil
France	Site No. 9006	Lille
France	Site 9012	Montpellier
France	Site No. 9008	Nantes
France	Site No. 9010	Nice
France	Site No. 9007	Paris
France	Site No. 9014	Paris
France	Site No. 9011	Rennes
France	Site No. 9001	Strasbourg
France	Site No. 9002	Toulouse
France	Site No. 9009	Vandœuvre-lès-Nancy
Germany	Site No. 9111	Aachen
Germany	Site No. 9113	Bonn
Germany	Site No. 9109	Dresden
Germany	Site No. 9108	Frankfurt am Main
Germany	Site No. 9106	Hamburg
Germany	Site No 9105	Hannöver
Germany	Site No. 9112	Heidelberg
Germany	Site No. 9101	Mainz
Germany	Site No. 9102	München
Germany	Site No. 9104	Tübingen
Germany	Site No. 9110	Ulm
Hong Kong	Site No. 8601	Hong Kong
Israel	Site No. 9707	Afula
Israel	Site 9704	Haifa
Israel	Site No. 9702	Haifa
Israel	Site No. 9705	Jerusalem
Israel	Site No. 9703	Ramat-Gan
Israel	Site No. 9706	Tel Aviv
Italy	Site No.9205	Modena
Italy	Site No. 9204	Napoli
Italy	Site No. 9201	Palermo
Italy	Site No. 9203	Parma
Korea, Republic of	Site No. 8208	Ansan
Korea, Republic of	Site No. 8211	Bucheon
Korea, Republic of	Site No. 8201	Busan
Korea, Republic of	Site 8216	Daegu
Korea, Republic of	Site No. 8207	Daegu
Korea, Republic of	Site No. 8213	Daegu
Korea, Republic of	Site No. 8220	Daegu
Korea, Republic of	Site 8224	Goyang
Korea, Republic of	Site No. 8221	Jinju-si
Korea, Republic of	Site No. 8218	Pusan
Korea, Republic of	Site No. 8222	Seongnam
Korea, Republic of	Site No. 8219	Seongnam-si
Korea, Republic of	Site No. 8202	Seoul
Korea, Republic of	Site No. 8203	Seoul
Korea, Republic of	Site No. 8205	Seoul
Korea, Republic of	Site No. 8209	Seoul
Korea, Republic of	Site No. 8212	Seoul
Korea, Republic of	Site No. 8215	Seoul
Korea, Republic of	Site No. 8223	Seoul
Korea, Republic of	Site No. 8210	Suwon
Korea, Republic of	Site No. 8217	Ulsan
New Zealand	Auckland City Hospital	Auckland
New Zealand	Site No. 8902	Christchurch
Portugal	Site No. 9404	Coimbra
Portugal	Site No. 9405	Coimbra
Portugal	Site No. 9403	Lisboa
Portugal	Site No. 9401	Porto
Portugal	Site No. 9402	Porto
Singapore	Site 8702	Singapore
Singapore	Site 8703	Singapore
Singapore	Site No. 8701	Singapore
Taiwan	Site No. 8305	Kaohsiung
Taiwan	Site No. 8307	Linkou
Taiwan	Site No. 8306	Taichung
Taiwan	Site No. 8302	Tainan City
Taiwan	Site No. 8301	Taipei
Taiwan	Site No. 8303	Taipei
Thailand	Site No. 8502	Bangkok
Thailand	Site No. 8505	Bangkok
Thailand	Site No. 8503	Chiang Mai
Thailand	Site No. 8507	Hat Yai
Thailand	Site No. 8501	Khon Kaen
Thailand	Site No. 8506	Phitsanulok
United Kingdom	Site No. 9501	Birmingham
United Kingdom	Site No. 9505	Guildford
United Kingdom	Site No. 9503	Leeds
United Kingdom	Site No. 9502	London
United Kingdom	Site No. 9504	London
United Kingdom	Site No. 9506	London
United States	Mercy Medical Center, Inc.	Baltimore	Maryland
United States	Billings Clinic	Billings	Montana
United States	University of Alabama	Birmingham	Alabama
United States	University of Chicago	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	University of Florida Shands Hospital	Gainesville	Florida
United States	Kansas City Research Institute	Kansas City	Missouri
United States	University of Kansas Cancer Center	Kansas City	Kansas
United States	University of Tennessee Medical Center	Knoxville	Tennessee
United States	University of Louisville	Louisville	Kentucky
United States	University of Minnesota	Minneapolis	Minnesota
United States	Morristown Medical Center	Morristown	New Jersey
United States	Tulane University Health Sciences Center	New Orleans	Louisiana
United States	UC Irvine Medical Center	Orange	California
United States	Stanford University School of Medicine	Palo Alto	California
United States	St. Joseph's Hospital	Paterson	New Jersey
United States	Hospital of The University of Pennsylvania	Philadelphia	Pennsylvania
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Saint Louis University	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Mayo Clinic Arizona	Scottsdale	Arizona
United States	Benaroya Research Institute at Virginia Mason Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
SillaJen, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  China,  France,  Germany,  Hong Kong,  Israel,  Italy,  Korea, Republic of,  New Zealand,  Portugal,  Singapore,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate (ORR)	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.	From date of randomization to the date of first documented radiographic tumor progression up to 53 months