Advanced Hepatocellular Carcinoma MedDRA version: 14.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: JX-594
Pharmaceutical Form: Solution for injection/infusion
CAS Number: 1058624-46-6
Current Sponsor code: JX-594
Other descriptive name: Recombinant Vaccinia GM-CSF
RAC VAC GM-CSF (Thymidine kinase-deactivated plus GM-CSF), VACC 6.25.1
Concentration unit: PFU/dose plaque forming unit(s)/dose
Concentration type: equal
Concentration number: 1000000000-
Sponsors
Jennerex, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Advanced HCC (excluding fibrolamellar carcinoma and hepatoblastoma): Patients are not eligible for, or had disease progression after, local-regional therapy (e.g., surgery, TACE, RFA, ethanol injection, e.g., BCLC Grade B or C [AASLD guidelines]) 2. Histological/cytological confirmation or clinical/laboratory diagnosis of primary HCC [clinical/laboratory diagnosis is defined according to the AASLD guidelines as the following: a. nodules larger than 2 cm in cirrhotic livers: with typical vascular features on a dynamic imaging technique (CT, contrast US or non-contrast MRI), or AFP >200 ng/ml; b. nodules between 1?2 cm in cirrhotic livers: with typical vascular features on 2 dynamic studies.] 3. Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites 4. Platelet count ?50,000 plts/mm3 5. INR ?1.7 6. Measurable tumor (at least one tumor with ?1 cm LD of contrast-enhancement during the arterial phase on CT scanning) 7. Expected survival of approximately 12 weeks or longer 8. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2 9. Aged ?18 years old 10. WBC count ?2,000 cells/mm3 and ?50,000 cells/mm3 11. Absolute neutrophil count (ANC) ?1,200 cells/mm3 12. Lymphocytes ?500 cells/mm3 13. Hemoglobin ?10 g/dL (correction with transfusion allowed) 14. Adequate liver function (albumin ?2.8 g/dL, total bilirubin ?3 mg/dL; ALT, AST ?5 x ULN) 15. Serum chemistries within normal limits or Grade 1 (excluding alkaline phosphatase) 16. For patients who are sexually active: patient must be able and willing to abstain for a minimum of 15 days after each treatment and subsequently use barrier method during JX 594 treatment period and for at least 6 weeks after the last JX 594 treatment 17. Written informed consent obtained from the patient 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 18 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1. Serum creatinine >2.0 mg/dL and/or creatinine clearance is <60 mL/min according to Cockroft-Gault formula 2. Significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or medication 3. History of severe exfoliative skin condition 4. Tumor(s) invading a major vascular structure 5. Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural effusions 6. Severe or unstable cardiac disease, including significant coronary artery disease within the preceding 12 months, unless well-controlled and on stable medical therapy for at least 3 months 7. Viable central nervous system (CNS) malignancy associated with clinical symptoms 8. Received sorafenib as previous treatment for HCC for more than 14 days 9. Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas) 10. Participation in any other research protocol involving an investigational medicinal product (IMP) within 2 months prior to first treatment 11. 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 12. Use of interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be discontinued within 14 days prior to any JX 594 dose. 13. Significant bleeding event within the last 12 months based on investigator assessment. 14. Inability to receive IV iodinated contrast agents for CT scanning due to documented history of iodinated contrast allergy unless controlled by medical intervention 15. Pregnant or nursing an infant 16. Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination 17. Patient unable or unwilling to comply with the protocol requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determine radiographic response rate (based on mRECIST for HCC and mChoi criteria).;Secondary Objective: ? Determine the safety of JX 594 administered by multiple IV infusions in patients with advanced HCC ? Determine time-to-tumor progression (TTP) on JX 594 therapy according to mRECIST criteria for HCC ? Determine overall survival (OS);Primary end point(s): Radiographic response rate (based on mRECIST for HCC and mChoi criteria) as determined by the independent central review (ICR).;Timepoint(s) of evaluation of this end point: Radiographic response rate (based on mRECIST for HCC and mChoi criteria): radiographic assessment every 6 weeks during study treatment and follow-up period, until tumour progression, patient withdrawal or death | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Safety of JX 594 according to National Cancer Institute ? Common Toxicity Criteria (NCI CTC) version 4.03 ? Time to progression based on mRECIST for HCC ? Overall survival duration;Timepoint(s) of evaluation of this end point: ? Safety: Safety assessment will be conducted at each study visit which means every week during study treatment and every 3 weeks during follow-up period until tumour progression, patient withdrawal or death ? Time to progression: CT scan every 6 weeks during study treatment and follow-up period, until tumour progression, patient withdrawal or death ? Overall survival duration: Followed for survival at each study visit during study participation and after discontinuation from the study, patients, and/or their specified contacts will continue to be contacted approximately every 4 weeks | — |
Countries
Hong Kong, Korea, Republic of, Spain, United States
Contacts
Public ContactMedical Affairs Secretariat
Transgene S.A.
Outcome results
None listed