A Phase 2b Study of Modified Vaccinia Virus to Treat Patients Advanced Liver Cancer Who Failed Sorafenib (TRAVERSE)
Primary Purpose
Hepatocellular Carcinoma, Liver Cancer, HCC
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
JX-594 recombinant vaccina GM-CSF
Best Supportive Care
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring liver cancer, liver tumor, advanced hcc, hepatocellular cancer, Jennerex, HCC, sorafenib, sorafenib failure, sorafenib intolerant, Nexavar, Nexavar failure, JX594, oncolytic virus, vaccinia, viral therapy, JX, Biotherapeutics, HEP018, traverse, biologic, Pexa-Vec
Eligibility Criteria
KEY Inclusion Criteria:
- Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis
- Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC
- ECOG performance status 0, 1 or 2
- Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
- Hematocrit ≥30% or Hemoglobin ≥10 g/dL
- Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited >25% growth in viable tumor size since prior local-regional treatment.
KEY Exclusion Criteria:
- Received sorafenib within 14 days prior to randomization
- Received systemic anti-cancer therapy other than sorafenib within 28 days of randomization
- Prior treatment with JX-594
- Platelet count < 50,000 PLT/ mm3
- Total white blood cell count < 2,000 cells/mm3
- Prior or planned organ transplant
- Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication
- Severe or unstable cardiac disease
- Viable CNS malignancy associated with clinical symptoms
- Pregnant or nursing an infant
- History of inflammatory skin condition (e.g., eczema requiring previous treatment, atopic dermatitis)
Sites / Locations
- Moores University of California San Diego Cancer Center
- Chao Family Comprehensive Cancer Center
- California Pacific Medical Center
- Stanford Hospital and Clinics
- University of Chicago Medical Center
- Billings Clinic
- Saint Joseph's Hospital
- Montefiore Medical Center
- Gabrail Cancer Center
- University Hospitals Case Medical Center
- The Methodist Hospital Department of Surgery
- University of Alberta
- University of British Columbia
- Juravinski Cancer Centre
- Ottawa Hopsital Research Institute
- Hôpitaux Universitaires de Strasbourg - Hôpital Civil
- Centre Hospitalier Universitaire Hôpital Saint André
- CHU d'Estaing
- Hôpital Saint Antoine, CPP Ile de France V
- Hôpital Purpan
- Hôpital de la Croix Rousse
- Klinikum Rechts der Isar der Technischen Universität München
- Medizinische Hochschule Hannover
- Johannes Gutenberg-Universität Mainz
- Universitätsklinikum Hamburg-Eppendorf
- Queen Mary Hospital
- Korea University Ansan Hospital
- Kyungpook National University Hospital
- Pusan National University Hospital
- Asan Medical Center
- Korea University Guro Hospital
- Samsung Medical Center
- Seoul National University Hospital
- Severance Hospital,Yonsei University Health System
- Pusan National University Yangsan Hospital
- National Cheng-Kung University Hospital
- National Taiwan University Hospital
- Taipei Veterans General Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
Arm A
Arm B
Arm Description
Patients on Arm A will receive 1 e9 pfu (plaque forming units) total dose of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) on each of six (6) treatments over 18 weeks.
Patients on the control arm (Arm B) will have best supportive care over 18 weeks.
Outcomes
Primary Outcome Measures
Survival
Determine overall survival for patients receiving JX-594 plus best supportive care (Arm A) compared with those patients receiving best supportive care (Arm B) in patients with advanced hepatocellular carcinoma (HCC) who have failed sorafenib treatment.
Secondary Outcome Measures
Time to Tumor Progression
Determine time-to-tumor-progression (TTP) for Arm A compared with Arm B based on mRECIST for HCC.
Quality of Life
Determine the Quality of Life (QoL) of patients treated in Arm A compared with Arm B.
Tumor Response
Determine tumor response based on mRECIST for HCC of Arm A versus Arm B
Safety profile of JX594
Safety will be assessed by the number of adverse events (AEs) and serious adverse events (SAEs)
Time-to-symptomatic-progression
Determine time to progression of Arm A compared to Arm B.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01387555
Brief Title
A Phase 2b Study of Modified Vaccinia Virus to Treat Patients Advanced Liver Cancer Who Failed Sorafenib
Acronym
TRAVERSE
Official Title
A Phase 2b Randomized Trial of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) Plus Best Supportive Care Versus Best Supportive Care in Patients With Advanced Hepatocellular Carcinoma Who Have Failed Sorafenib Treatment
Study Type
Interventional
2. Study Status
Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
December 2008 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jennerex Biotherapeutics
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is to determine whether JX-594 (Pexa-Vec) plus best supportive care is more effective in improving survival than best supportive care in patients with advanced Hepatocellular Carcinoma (HCC) who have failed sorafenib.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma, Liver Cancer, HCC
Keywords
liver cancer, liver tumor, advanced hcc, hepatocellular cancer, Jennerex, HCC, sorafenib, sorafenib failure, sorafenib intolerant, Nexavar, Nexavar failure, JX594, oncolytic virus, vaccinia, viral therapy, JX, Biotherapeutics, HEP018, traverse, biologic, Pexa-Vec
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
129 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A
Arm Type
Experimental
Arm Description
Patients on Arm A will receive 1 e9 pfu (plaque forming units) total dose of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) on each of six (6) treatments over 18 weeks.
Arm Title
Arm B
Arm Type
Other
Arm Description
Patients on the control arm (Arm B) will have best supportive care over 18 weeks.
Intervention Type
Biological
Intervention Name(s)
JX-594 recombinant vaccina GM-CSF
Intervention Description
Patients will be randomised 2:1 to Arm A or Arm B and will receive 6 treatments on days 1, 8, 22, week 6, week 12, and week 18 plus best supportive care as needed.
Intervention Type
Other
Intervention Name(s)
Best Supportive Care
Intervention Description
Patients will be randomised 2:1 to Arm A or Arm B and will receive best supportive care as needed.
Primary Outcome Measure Information:
Title
Survival
Description
Determine overall survival for patients receiving JX-594 plus best supportive care (Arm A) compared with those patients receiving best supportive care (Arm B) in patients with advanced hepatocellular carcinoma (HCC) who have failed sorafenib treatment.
Time Frame
CT scan every six weeks until progression or death, assessed up to 21 months
Secondary Outcome Measure Information:
Title
Time to Tumor Progression
Description
Determine time-to-tumor-progression (TTP) for Arm A compared with Arm B based on mRECIST for HCC.
Time Frame
CT scan every six weeks until progression or death, assessed up to 21 months
Title
Quality of Life
Description
Determine the Quality of Life (QoL) of patients treated in Arm A compared with Arm B.
Time Frame
assessed up to 21 months (average)
Title
Tumor Response
Description
Determine tumor response based on mRECIST for HCC of Arm A versus Arm B
Time Frame
CT scan every 6 weeks until progression or death, assessed up to 21 months (average)
Title
Safety profile of JX594
Description
Safety will be assessed by the number of adverse events (AEs) and serious adverse events (SAEs)
Time Frame
assessed up to 21 months (average)
Title
Time-to-symptomatic-progression
Description
Determine time to progression of Arm A compared to Arm B.
Time Frame
assessed up to 21 months (average)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
KEY Inclusion Criteria:
Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis
Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC
ECOG performance status 0, 1 or 2
Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
Hematocrit ≥30% or Hemoglobin ≥10 g/dL
Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited >25% growth in viable tumor size since prior local-regional treatment.
KEY Exclusion Criteria:
Received sorafenib within 14 days prior to randomization
Received systemic anti-cancer therapy other than sorafenib within 28 days of randomization
Prior treatment with JX-594
Platelet count < 50,000 PLT/ mm3
Total white blood cell count < 2,000 cells/mm3
Prior or planned organ transplant
Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication
Severe or unstable cardiac disease
Viable CNS malignancy associated with clinical symptoms
Pregnant or nursing an infant
History of inflammatory skin condition (e.g., eczema requiring previous treatment, atopic dermatitis)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
James Burke, MD
Organizational Affiliation
Jennerex Biotherapeutics
Official's Role
Study Director
Facility Information:
Facility Name
Moores University of California San Diego Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
Chao Family Comprehensive Cancer Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
California Pacific Medical Center
City
San Francisco
State/Province
California
Country
United States
Facility Name
Stanford Hospital and Clinics
City
Stanford
State/Province
California
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
Billings Clinic
City
Billings
State/Province
Montana
Country
United States
Facility Name
Saint Joseph's Hospital
City
Paterson
State/Province
New Jersey
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
Country
United States
Facility Name
University Hospitals Case Medical Center
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
The Methodist Hospital Department of Surgery
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2B7
Country
Canada
Facility Name
University of British Columbia
City
Vancouver
State/Province
British Columbia
Country
Canada
Facility Name
Juravinski Cancer Centre
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
Ottawa Hopsital Research Institute
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Hôpitaux Universitaires de Strasbourg - Hôpital Civil
City
Strasbourg Cedex
State/Province
Alsace
ZIP/Postal Code
67091
Country
France
Facility Name
Centre Hospitalier Universitaire Hôpital Saint André
City
Bordeaux
State/Province
Aquitaine
ZIP/Postal Code
33000
Country
France
Facility Name
CHU d'Estaing
City
Clermont-Ferrand
State/Province
Auvergne
ZIP/Postal Code
63003
Country
France
Facility Name
Hôpital Saint Antoine, CPP Ile de France V
City
Paris
State/Province
Ile-de-France
ZIP/Postal Code
75571
Country
France
Facility Name
Hôpital Purpan
City
Toulouse
State/Province
Midi-Pyrenees
ZIP/Postal Code
31059
Country
France
Facility Name
Hôpital de la Croix Rousse
City
Lyon Cedex
State/Province
Rhone-Alpes
ZIP/Postal Code
69317
Country
France
Facility Name
Klinikum Rechts der Isar der Technischen Universität München
City
München
State/Province
Bayern
ZIP/Postal Code
81675
Country
Germany
Facility Name
Medizinische Hochschule Hannover
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
Johannes Gutenberg-Universität Mainz
City
Mainz
State/Province
Rheinland-Pfalz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Universitätsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Korea University Ansan Hospital
City
Ansan-si
State/Province
Gyeonggi-Do
ZIP/Postal Code
425-707
Country
Korea, Republic of
Facility Name
Kyungpook National University Hospital
City
Daegu
Country
Korea, Republic of
Facility Name
Pusan National University Hospital
City
Pusan
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
138-736
Country
Korea, Republic of
Facility Name
Korea University Guro Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Facility Name
Severance Hospital,Yonsei University Health System
City
Seoul
Country
Korea, Republic of
Facility Name
Pusan National University Yangsan Hospital
City
Yangsan
Country
Korea, Republic of
Facility Name
National Cheng-Kung University Hospital
City
TPE
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
TPE
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
TPE
Country
Taiwan
12. IPD Sharing Statement
Citations:
PubMed Identifier
31413923
Citation
Moehler M, Heo J, Lee HC, Tak WY, Chao Y, Paik SW, Yim HJ, Byun KS, Baron A, Ungerechts G, Jonker D, Ruo L, Cho M, Kaubisch A, Wege H, Merle P, Ebert O, Habersetzer F, Blanc JF, Rosmorduc O, Lencioni R, Patt R, Leen AM, Foerster F, Homerin M, Stojkowitz N, Lusky M, Limacher JM, Hennequi M, Gaspar N, McFadden B, De Silva N, Shen D, Pelusio A, Kirn DH, Breitbach CJ, Burke JM. Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE). Oncoimmunology. 2019 Jun 3;8(8):1615817. doi: 10.1080/2162402X.2019.1615817. eCollection 2019.
Results Reference
derived
Links:
URL
http://www.jennerex.com
Description
Sponsor Website
Learn more about this trial
A Phase 2b Study of Modified Vaccinia Virus to Treat Patients Advanced Liver Cancer Who Failed Sorafenib
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