Clinical Trials List
Protocol NumberJX594-HEP024
NCT Number(ClinicalTrials.gov Identfier)NCT02562755
2015-12-01 - 2020-04-30
Phase III
Terminated6
ICD-10C22.0
Liver cell carcinoma
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
-
Trial Applicant
PPD DEVELOPMENT (HK) LIMITED
-
Sponsor
SillaJen Inc.
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 郭垣宏 Digestive System Department
- Jing-Houng Wang Digestive System Department
- 洪肇宏 Digestive System Department
- 許獻文 Division of Radiology
- 紀廣明 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 呂宜達 Digestive System Department
- 陳家昌 Digestive System Department
- 葉宏仁 Digestive System Department
- 張碧倚 Division of Radiology
- 黃振義 Division of Radiology
- CHUNG-HSIN CHANG Digestive System Department
- TENG-YU LEE Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 邱怡友 Division of Radiology
- Yi-Ping Hung Division of Hematology & Oncology
- Chien-An Liu Division of Radiology
- Chung-Pin Li Digestive System Department
- Ming-Huang Chen Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Principal Investigator
Co-Principal Investigator
- Ming-Mo Hou Division of Hematology & Oncology
- Tsai-Sheng Yang Division of Hematology & Oncology
- Jen-Shi Chen Division of Hematology & Oncology
- 呂嘉偉 Division of Radiology
- Mengting Peng Division of Hematology & Oncology
- Chia-Hsun Hsieh Division of Hematology & Oncology
- Cheng-Lung Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 邱彥程 Digestive System Department
- Liu Yi-Sheng Digestive System Department
- Pin-Nan Cheng Digestive System Department
- 吳毅晉 Digestive System Department
- Chiu Hung Chiu Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 施怡倫 Division of Radiology
- JA-DER LIANG Digestive System Department
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
Advanced Hepatocellular Carcinoma (HCC) Without Prior Systemic Therapy
Objectives
Primary Objective
• To determine and compare the overall survival of patients with advanced HCC
without prior systemic therapy, treated with Pexa-Vec followed by sorafenib
(Arm A) versus sorafenib (Arm B)
Secondary Objectives:
• To determine and compare the 2 treatment arms response based on central
assessments using modified Response Evaluation Criteria In Solid Tumors
(mRECIST) for HCC for the following endpoints:
Time-to-progression (TTP)
Progression free survival (PFS)
Overall response rate (ORR)
Disease control rate (DCR)
• To determine and compare the safety profiles of the 2 treatment arms
• To determine and compare the time-to-symptomatic progression (TSP) of the
2 treatment arms
• To determine and compare the Quality of Life (QoL) of the 2 treatment arms
Test Drug
Pexastimogene Devacirepvec (Pexa Vec)
Active Ingredient
Pexastimogene Devacirepvec (Pexa Vec)
Dosage Form
Injection
Dosage
2.0 ml/bottle
Endpoints
For secondary endpoints, central radiological assessments will be evaluated with
mRECIST for HCC.
For exploratory endpoints, local and central radiological assessments will be used
and evaluated with RECIST 1.1.
Primary Endpoint:
• Overall Survival: time from date of randomization to the date of death due to
any cause. If a patient is not known to have died at the cut-off date for
analysis, survival will be censored at the date of last contact.
Secondary Endpoints:
• Time to Progression (TTP): time from randomization to the date of first
documented radiographic tumor progression; TTP does not include deaths. If
a patient has not had a TTP event at the cut-off date for analysis, TTP will be
censored at the date of last evaluable tumor assessment before the cut-off.
• Progression Free Survival (PFS): time from randomization to the date of first
documented radiographic tumor progression or death due to any cause,
whichever occurs first. If a patient has not had a PFS event at the cut-off date
for analysis, PFS will be censored at the date of last evaluable tumor
assessment before the cut-off.
• Overall response rate (ORR): proportion of patients whose best overall
response during their participation in the study is either CR or PR. The best
overall response is the best response recorded from the randomization until
disease progression.
• Disease control rate (DCR): proportion of patients whose best overall
response during their participation in the study is either CR, PR, or stable
disease (SD).
• Safety: assessed by the NCI CTCAE (version 4.03). Incidence of AEs and
SAEs will be reported.
• Time to Symptomatic Progression (TSP): time from randomization until the first
documented event of symptomatic progression defined as a decrease of
4 points or more from baseline in the FHSI-8 questionnaire (sub-part of the
FACT-Hep questionnaire) or a decrease in performance status to 4, or death.
• Changes in the QoL assessed by changes in the FACT-Hep and EQ5D-3L
questionnaires.
mRECIST for HCC.
For exploratory endpoints, local and central radiological assessments will be used
and evaluated with RECIST 1.1.
Primary Endpoint:
• Overall Survival: time from date of randomization to the date of death due to
any cause. If a patient is not known to have died at the cut-off date for
analysis, survival will be censored at the date of last contact.
Secondary Endpoints:
• Time to Progression (TTP): time from randomization to the date of first
documented radiographic tumor progression; TTP does not include deaths. If
a patient has not had a TTP event at the cut-off date for analysis, TTP will be
censored at the date of last evaluable tumor assessment before the cut-off.
• Progression Free Survival (PFS): time from randomization to the date of first
documented radiographic tumor progression or death due to any cause,
whichever occurs first. If a patient has not had a PFS event at the cut-off date
for analysis, PFS will be censored at the date of last evaluable tumor
assessment before the cut-off.
• Overall response rate (ORR): proportion of patients whose best overall
response during their participation in the study is either CR or PR. The best
overall response is the best response recorded from the randomization until
disease progression.
• Disease control rate (DCR): proportion of patients whose best overall
response during their participation in the study is either CR, PR, or stable
disease (SD).
• Safety: assessed by the NCI CTCAE (version 4.03). Incidence of AEs and
SAEs will be reported.
• Time to Symptomatic Progression (TSP): time from randomization until the first
documented event of symptomatic progression defined as a decrease of
4 points or more from baseline in the FHSI-8 questionnaire (sub-part of the
FACT-Hep questionnaire) or a decrease in performance status to 4, or death.
• Changes in the QoL assessed by changes in the FACT-Hep and EQ5D-3L
questionnaires.
Inclution Criteria
Inclusion Criteria:
1. Male or female patients, age ≥18 years old
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)
eligible for systemic therapy excluding cholangiocarcinoma,
hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma
4. Tumor status (as determined by radiology evaluation): 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. At least one tumor that has not received prior local-regional treatment, or that
has exhibited >25% increase in viable tumor size since prior local-regional
treatment
6. Child-Pugh Class A. NOTE: paracentesis, albumin infusion or diuretic
treatment cannot be used to downgrade Child-Pugh score (e.g., to improve
from severe to moderate/mild or from moderate to mild ascites)
7. Performance status 0 or 1 on the Eastern Cooperative Oncology Group
(ECOG) scale
8. Adequate hematological, hepatic, and renal function:
a. Hemoglobin ≥9 g/dL
b. Platelet count ≥75 x 109
/L
c. International normalized ratio (INR) ≤1.7
d. White blood cell (WBC) count ≥2 x 109
/L
e. Absolute neutrophil count (ANC) ≥1 x 109
/L
f. Albumin ≥2.8 g/dL, total bilirubin ≤3.0 mg/dL (51.3 µmol/L); alanine
aminotransferase (ALT), aspartate transaminase (AST) ≤5 times upper
limit of normal (ULN)
g. Serum chemistries sodium, potassium, and calcium within normal limits
(WNL) or Grade 1
h. Serum creatinine <2.0 mg/dL or creatinine clearance >60 mL/min
according to Cockroft-Gault formula
9. For patients who are sexually active: willing to use adequate barrier
contraception method for at least 6 weeks after each treatment of Pexa-Vec,
during sorafenib treatment, and for 2 weeks after sorafenib discontinuation
10. Life expectancy of at least 3 months
11. Written informed consent
1. Male or female patients, age ≥18 years old
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)
eligible for systemic therapy excluding cholangiocarcinoma,
hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma
4. Tumor status (as determined by radiology evaluation): 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. At least one tumor that has not received prior local-regional treatment, or that
has exhibited >25% increase in viable tumor size since prior local-regional
treatment
6. Child-Pugh Class A. NOTE: paracentesis, albumin infusion or diuretic
treatment cannot be used to downgrade Child-Pugh score (e.g., to improve
from severe to moderate/mild or from moderate to mild ascites)
7. Performance status 0 or 1 on the Eastern Cooperative Oncology Group
(ECOG) scale
8. Adequate hematological, hepatic, and renal function:
a. Hemoglobin ≥9 g/dL
b. Platelet count ≥75 x 109
/L
c. International normalized ratio (INR) ≤1.7
d. White blood cell (WBC) count ≥2 x 109
/L
e. Absolute neutrophil count (ANC) ≥1 x 109
/L
f. Albumin ≥2.8 g/dL, total bilirubin ≤3.0 mg/dL (51.3 µmol/L); alanine
aminotransferase (ALT), aspartate transaminase (AST) ≤5 times upper
limit of normal (ULN)
g. Serum chemistries sodium, potassium, and calcium within normal limits
(WNL) or Grade 1
h. Serum creatinine <2.0 mg/dL or creatinine clearance >60 mL/min
according to Cockroft-Gault formula
9. For patients who are sexually active: willing to use adequate barrier
contraception method for at least 6 weeks after each treatment of Pexa-Vec,
during sorafenib treatment, and for 2 weeks after sorafenib discontinuation
10. Life expectancy of at least 3 months
11. Written informed consent
Exclusion Criteria
Exclusion Criteria:
1. Major surgery within 4 weeks of study treatments (minor surgical procedures
are allowed e.g., intravascular access line or Port-a-Cath®)
2. Local-regional therapy of HCC within 4 weeks prior to randomization
3. Histological diagnosis of cholangiocarcinoma, hepatocholangiocarcinoma,
fibrolamellar carcinoma and hepatoblastoma
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
(defined as ≥20 mg/day prednisone or equivalent which is ongoing at the time
of randomization and/or was taken for more than 4 weeks within the preceding
2 months of study treatment)
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. Tumor(s) invading a major vascular structure (e.g., carotid artery) or other key
anatomical structure (e.g., pulmonary airway) in the event of post-injection
tumor swelling and/or necrosis (hepatic and portal vein involvement allowed)
10. Clinically significant and/or rapidly accumulating ascites, pericardial and/or
pleural effusions. Mild ascites that does not preclude safe IT injection of
Pexa-Vec is allowed at the discretion of the treating physician.
11. 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
12. 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
13. Medical conditions, per the investigator’s judgment, that predispose the patient
to untoward medical risk in the event of volume loading (e.g., intravenous [IV]
fluid bolus infusion), tachycardia, or hypotension during or following treatment
with Pexa-Vec
14. Viable central nervous system malignancy (history of completely resected or
irradiated brain metastases allowed)
15. Prior systemic therapy for HCC (NOTE: Patients receiving 7 days or less
exposure to systemic therapy are allowed)
16. Known contraindications to sorafenib according to the drug prescribing
information and/or severe hypersensitivity to sorafenib or any other component
of sorafenib, or known intolerance to sorafenib
17. Other medical condition or laboratory abnormality or active infection that in the
judgment of the Principal Investigator may increase the risk associated with
study participation or may interfere with interpretation of study results and/or
otherwise make the patient inappropriate for entry into this study
18. Hepatitis C virus therapy including interferon/pegylated interferon or ribavirin
that cannot be discontinued within 14 days prior to any Pexa-Vec injection.
Medical Monitor should be consulted if the patient is taking any other antiviral
medications to determine eligibility.
19. No prior malignancy except for the following: adequately treated basal or
squamous cell skin cancer, in situ cervical cancer, adequately treated cancer
from which the patient has been disease-free for at least 3 years
20. Significant bleeding event within the last 12 months that places the patient at
risk for intrahepatic IT injection procedure based on Investigator assessment
21. Anticoagulant or anti-platelet medication that cannot be interrupted prior to
Pexa-Vec IT injections, including:
• Aspirin that cannot be discontinued for 7 days prior to Pexa-Vec IT
injections
• Coumadin that cannot be discontinued for 7 days prior to Pexa-Vec IT
injections
• Low molecular weight heparin (LMWH) that cannot be discontinued
>24 hours prior to Pexa-Vec IT injections
• Unfractionated heparin (UFH) that cannot be discontinued >4 hours prior
to Pexa-Vec IT injection
• Oral direct thrombin inhibitor (dabigatran) or direct Factor Xa inhibitor
(rivaroxaban, apixiban, and endoxaban) that cannot be discontinued for
4 days prior to Pexa-Vec IT injection
NOTE: LMWH or UFH may be used to transition patients on and off of the above
anti-coagulants (if deemed appropriate by the treating physician) prior to
Pexa-Vec treatments as long as the last dose of LMWH is administered
>24 hours prior to treatments and last dose of UFH is administered
>4 hours prior to treatments.
Please contact the Sponsor for questions regarding the management of other
anticoagulant prior to treatments.
22. Inability to suspend treatment with anti-hypertensive medication (including but
not limited to: diuretics, beta-blockers, angiotensin converting enzyme [ACE]
inhibitors, aldosterone antagonists, etc.) for 48 hours prior to and 48 hours
after each Pexa-Vec injection.
23. Any prior or planned organ transplant (e.g., liver transplant)
24. Pregnant or nursing (lactating) women, where pregnancy is defined as the
state of a female after conception and until the termination of gestation. Childbearing potential patients with a positive hCG laboratory test (>10 mIU/mL) at
screening and/or a urinary pregnancy test at Baseline will perform an
ultrasound to confirm the pregnancy.
25. Patients who experienced a severe systemic reaction or side-effect as a result
of a previous vaccination with vaccinia
26. Participation in a clinical study and treatment with an active IP within 4 weeks
prior to randomization
27. Patient unable or unwilling to comply with the protocol requirements
28. Previous treatment with Pexa-Vec or other vaccinia vector based treatment
29. Pulse oximetry O2 saturation <90% at rest on room air
1. Major surgery within 4 weeks of study treatments (minor surgical procedures
are allowed e.g., intravascular access line or Port-a-Cath®)
2. Local-regional therapy of HCC within 4 weeks prior to randomization
3. Histological diagnosis of cholangiocarcinoma, hepatocholangiocarcinoma,
fibrolamellar carcinoma and hepatoblastoma
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
(defined as ≥20 mg/day prednisone or equivalent which is ongoing at the time
of randomization and/or was taken for more than 4 weeks within the preceding
2 months of study treatment)
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. Tumor(s) invading a major vascular structure (e.g., carotid artery) or other key
anatomical structure (e.g., pulmonary airway) in the event of post-injection
tumor swelling and/or necrosis (hepatic and portal vein involvement allowed)
10. Clinically significant and/or rapidly accumulating ascites, pericardial and/or
pleural effusions. Mild ascites that does not preclude safe IT injection of
Pexa-Vec is allowed at the discretion of the treating physician.
11. 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
12. 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
13. Medical conditions, per the investigator’s judgment, that predispose the patient
to untoward medical risk in the event of volume loading (e.g., intravenous [IV]
fluid bolus infusion), tachycardia, or hypotension during or following treatment
with Pexa-Vec
14. Viable central nervous system malignancy (history of completely resected or
irradiated brain metastases allowed)
15. Prior systemic therapy for HCC (NOTE: Patients receiving 7 days or less
exposure to systemic therapy are allowed)
16. Known contraindications to sorafenib according to the drug prescribing
information and/or severe hypersensitivity to sorafenib or any other component
of sorafenib, or known intolerance to sorafenib
17. Other medical condition or laboratory abnormality or active infection that in the
judgment of the Principal Investigator may increase the risk associated with
study participation or may interfere with interpretation of study results and/or
otherwise make the patient inappropriate for entry into this study
18. Hepatitis C virus therapy including interferon/pegylated interferon or ribavirin
that cannot be discontinued within 14 days prior to any Pexa-Vec injection.
Medical Monitor should be consulted if the patient is taking any other antiviral
medications to determine eligibility.
19. No prior malignancy except for the following: adequately treated basal or
squamous cell skin cancer, in situ cervical cancer, adequately treated cancer
from which the patient has been disease-free for at least 3 years
20. Significant bleeding event within the last 12 months that places the patient at
risk for intrahepatic IT injection procedure based on Investigator assessment
21. Anticoagulant or anti-platelet medication that cannot be interrupted prior to
Pexa-Vec IT injections, including:
• Aspirin that cannot be discontinued for 7 days prior to Pexa-Vec IT
injections
• Coumadin that cannot be discontinued for 7 days prior to Pexa-Vec IT
injections
• Low molecular weight heparin (LMWH) that cannot be discontinued
>24 hours prior to Pexa-Vec IT injections
• Unfractionated heparin (UFH) that cannot be discontinued >4 hours prior
to Pexa-Vec IT injection
• Oral direct thrombin inhibitor (dabigatran) or direct Factor Xa inhibitor
(rivaroxaban, apixiban, and endoxaban) that cannot be discontinued for
4 days prior to Pexa-Vec IT injection
NOTE: LMWH or UFH may be used to transition patients on and off of the above
anti-coagulants (if deemed appropriate by the treating physician) prior to
Pexa-Vec treatments as long as the last dose of LMWH is administered
>24 hours prior to treatments and last dose of UFH is administered
>4 hours prior to treatments.
Please contact the Sponsor for questions regarding the management of other
anticoagulant prior to treatments.
22. Inability to suspend treatment with anti-hypertensive medication (including but
not limited to: diuretics, beta-blockers, angiotensin converting enzyme [ACE]
inhibitors, aldosterone antagonists, etc.) for 48 hours prior to and 48 hours
after each Pexa-Vec injection.
23. Any prior or planned organ transplant (e.g., liver transplant)
24. Pregnant or nursing (lactating) women, where pregnancy is defined as the
state of a female after conception and until the termination of gestation. Childbearing potential patients with a positive hCG laboratory test (>10 mIU/mL) at
screening and/or a urinary pregnancy test at Baseline will perform an
ultrasound to confirm the pregnancy.
25. Patients who experienced a severe systemic reaction or side-effect as a result
of a previous vaccination with vaccinia
26. Participation in a clinical study and treatment with an active IP within 4 weeks
prior to randomization
27. Patient unable or unwilling to comply with the protocol requirements
28. Previous treatment with Pexa-Vec or other vaccinia vector based treatment
29. Pulse oximetry O2 saturation <90% at rest on room air
The Estimated Number of Participants
-
Taiwan
25 participants
-
Global
600 participants
