E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced hepatocellular carcinoma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019828 |
E.1.2 | Term | Hepatocellular carcinoma non-resectable |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Determine overall survival (OS) for patients receiving JX-594 plus best supportive care (BSC) (Arm A) compared with those receiving BSC (Arm B) in patients with advanced hepatocellular carcinoma (HCC) who have failed sorafenib treatment. |
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E.2.2 | Secondary objectives of the trial |
- Determine time-to-tumor-progression (TTP) for Arm A compared with 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). |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Hospital staff exposure sub-study and JX-594 shedding sub-study, 2011-09-12, amdt 1.
The objective of hospital staff exposure sub-study is to get an indication of unintentional exposure and/or infection of care-givers by JX-594. The objective of the shedding sub-study is to detect shedding of infectious product. |
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E.3 | Principal inclusion criteria |
•Advanced HCC: patients are not eligible for, or had disease progression after, local-regional therapy (e.g. surgery, TACE, RFA, ethanol injection)
•Diagnosis of primary HCC by tissue biopsy, or clinical diagnosis based on EASL-EORTC guidelines
•Previously treated with sorafenib and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression
•Any side-effects from previous sorafenib therapy have resolved to Grade 1 or better, or are well-controlled with medication in the opinion of the Investigator
•ECOG performance status 0, 1 or 2
•Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
•Serum creatinine ≤2.0 mg/dL or creatinine clearance ≥60 mL/min according to Cockroft-Gault formula.
•Hematocrit ≥30% or Hemoglobin ≥10 g/dL (correction with transfusion or erythropoietin based therapy allowed to meet eligibility criteria)
•No ongoing (other than HCC) or prior malignancy except for the following: dequately 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 3 years.
•For patients who are sexually active: patient must be able and willing to abstain for a minimum of 3 weeks after each treatment and subsequently use barrier contraception method for at least 6 weeks after each treatment of JX-594
•Tumor status (as determined by radiology evaluation):
- Measurable viable tumor in the liver (≥1 cm longest diameter [LD] and enhancing on arterial phase of triphasic CT scan or MRI), and injectable under imaging-guidance (CT and/or ultrasound)
- At least one intrahepatic tumor that has not received prior local-regional treatment, or that has exhibited >25% increase in viable tumor size since prior local-regional treatment |
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E.4 | Principal exclusion criteria |
•Major surgery within 28 days of randomization or subcutaneous venous access device placement within 7 days prior to randomization
•Locoregional therapy within 28 days prior to randomization
•Received sorafenib within 14 days prior to randomization
•Received systemic anti-cancer therapy other than sorafenib within 28 days of randomization (6 weeks in case of mitomycin C or nitrosoureas)
•Prior treatment with JX-594
•Prior or planned organ transplant
•Platelet count < 50,000 PLT/ mm3
•Total white blood cell (WBC) count < 2,000 cells/mm3
•Prior or planned organ transplant (e.g. liver transplant)
•Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication
•History of inflammatory skin condition
•Severe or unstable cardiac disease
•Viable CNS malignancy associated with clinical symptoms
•Anticoagulant or anti-platelet medication that cannot be interrupted prior to IT injection
•Pregnant or breastfeeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
CT scan every six weeks until progression or death |
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E.5.2 | Secondary end point(s) |
Time-to-tumor progression, tumor response, time-to-symptomatic-progression duration, change in quality of life, safety and toxicity. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Time to Tumor Progression: CT scan every six weeks until progression or death, assessed up to 21 months (average)
•Quality of Life: assessed up to 21 months (average)
•Tumor Response: CT scan every 6 weeks until progression or death, assessed up to 21 months (average)
•Safety profile of JX594: assessed up to 21 months (average)
•Time-to-symptomatic-progression: assessed up to 21 months (average) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Best Supportive Care (BSC) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Hong Kong |
Korea, Republic of |
Russian Federation |
Taiwan |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 21 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 21 |
E.8.9.2 | In all countries concerned by the trial days | 0 |