Phase 2 Study of recombinant vaccinia virus in Sorafenib-naïve patients with Advanced liver cancer.

• Conditions: Advanced Hepatocellular Carcinoma; MedDRA version: 14.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectableSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-000591-42-ES
• Lead Sponsor: Jennerex, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07-26
• Last Update Posted: 10 March 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

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

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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<br>? Determine time-to-tumor progression (TTP) on JX 594 therapy according to mRECIST criteria for HCC <br>? 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 Outcome Measures

Name	Time	Method
Secondary end point(s): ? Safety of JX 594 according to National Cancer Institute ? Common Toxicity Criteria (NCI CTC) version 4.03<br>? Time to progression based on mRECIST for HCC<br>? 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<br>? Time to progression: CT scan every 6 weeks during study treatment and follow-up period, until tumour progression, patient withdrawal or death<br>? 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