A Phase 2b Study of Modified Vaccinia Virus to Treat Patients Advanced Liver Cancer Who Failed Sorafenib
- Conditions
- Neoplasms
- Registration Number
- KCT0000519
- Lead Sponsor
- Jennerex
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 40
· Advanced or intermediate stage HCC (Barcelona Clinic Liver Cancer [BCLC] Stage C or B per American Association for the Study of Liver Disease [AASLD] guidelines), excluding fibrolamellar carcinoma and hepatoblastoma. Patients must not be eligible for, or had disease progression after, local-regional therapy (e.g., surgery, transarterial chemoembolization [TACE], radiofrequency ablation [RFA], ethanol injection).
· Histologic or cytologic confirmation of primary HCC
· Previously treated with sorafenib for =14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either:
- Intolerance despite treatment at doses less than the maximum approved dosage of sorafenib (400 mg twice daily [bid]), either reduced dosage or frequency, or
- Radiographic progression during sorafenib treatment, or within 3 months or less after the last dose of sorafenib (regardless of response to sorafenib)
· Received sorafenib as the most recent therapeutic intervention
· Side-effects from previous sorafenib therapy have resolved to Grade 1 or better
· Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
· Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
· Adequate liver function (albumin =2.8 g/dL, total bilirubin =3 mg/dL [51.3 µmol/L]; alanine aminotransferase [ALT], aspartate transaminase [AST] =5 x upper limit of normal [ULN])
· No prior malignancy except for the following: adequately treated basal or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or Stage II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years
· 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 the treatment period and for at least 6 weeks after the last treatment
· Life expectancy of at least 3 months
· At least 18 years of age
· Written informed consent obtained from patient
Tumor status:
· Measurable viable tumor in the liver (=1 cm longest diameter [LD] and enhancing on arterial phase of triphasic computerized tomography [CT] scan), and injectable under imaging-guidance (CT and/or ultrasound)
· 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
· Major surgery within 28 days of randomization or subcutaneous venous access device placement within 7 days prior to randomization
· Local-regional therapy within 28 days prior to randomization
· Received sorafenib within 14 days prior to randomization
· Received systemic therapy other than sorafenib within 28 days of randomization
· Prior treatment with JX 594
· Platelet count <50,000 mm3 (correction with platelet transfusion allowed to meet eligibility criteria)
· International normalized ratio (INR) =1.7 (correction with plasma protein support allowed to meet eligibility criteria, e.g., fresh-frozen plasma)
· Serum creatinine >2.0 mg/dL or creatinine clearance is <60 mL/min according to Cockroft-Gault formula
· Total white blood cell count <2,000 cells/mm3 (correction with granulocyte colony stimulating factor [G-CSF] treatment allowed to meet eligibility criteria)
· Hematocrit <30% and/or Hemoglobin <10 g/dL (correction with transfusion or erythropoietin based therapy allowed to meet eligibility criteria)
· Inability to receive intravenous (IV) iodinated contrast agents for CT scanning due to documented history of iodinated contrast allergy, despite adequate treatment with anti-histamines and steroids or similar regimen
· Known significant immunodeficiency due to underlying illness (e.g., HIV/AIDS) and/or medication (e.g., high dose systemic corticosteroids taken for more than 4 weeks within the preceding 3 months)
· History of severe exfoliative skin condition (e.g., eczema or ectopic dermatitis requiring systemic therapy for more than 4 weeks)
· Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination
· Severe or unstable cardiac disease, including significant coronary artery disease requiring angioplasty or stenting within the preceding 12 months, unless well-controlled and on stable medical therapy for at least 3 months
· Viable central nervous system (CNS) malignancy associated with clinical symptoms (history of completely resected or irradiated brain metastases allowed)
· Chronic use of full-dose anti-platelet or anti-coagulation medication that cannot be temporarily discontinued for at least 7 days prior to intratumoral (IT) injection procedures on study. (NOTE: low-dose heparin to maintain port access allowed; low-dose aspirin [=100 mg daily] allowed)
· Patients with Hepatitis C virus who are on interferon/PEG-IFN and/or ribavirin within 14 days of Day 1 Visit.
· Other medical condition or laboratory abnormality or active infection that may increase the risk associated with study participation or may interfere with interpretation of study results and in the judgment of the Investigator would make the patient inappropriate for entry into this study
· Pregnant or nursing an infant
Study & Design
- Study Type
- Interventional Study
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Determine and compare overall survival for patients receiving JX 594 plus best supportive care (BSC) (Arm A) versus those receiving BSC (Arm B) in patients
- Secondary Outcome Measures
Name Time Method Determine and compare time-to-tumor-progression (TTP) for Arm A versus Arm B based on modified RECIST (mRECIST) for HCC.;Determine the response rate for Arm A compared with Arm B based on mRECIST for HCC.;Determine time-to-symptomatic progression (TSP) for Arm A compared with Arm B;Determine the Quality of Life (QoL) of patients treated in Arm A compared with Arm B.;Determine the safety and tolerability of JX 594 plus BSC (Arm A) compared to BSC (Arm B).