Pexa-Vec (a virus engineered to fight liver cancer) in combination with sorafenib (a pill for liver cancer) compared to sorafenib alone for advanced liver cancer

Phase 1

Conditions: Advanced Hepatocellular Carcinoma (HCC) without prior systemic therapy
MedDRA version: 20.0 Level: PT Classification code 10073071 Term: Hepatocellular carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2014-001985-86-PT

Lead Sponsor: SillaJen Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 600

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
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 300

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 and/or immune-suppressive medication including high-dose corticosteroids
7. Ongoing severe inflammatory skin condition requiring medical treatment
8. History of severe eczema 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
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.
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 i

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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