E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients >18 years with hepatocellular carcinoma, on waiting list for liver transplantation |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019829 |
E.1.2 | Term | Hepatocellular carcinoma recurrent |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10019830 |
E.1.2 | Term | Hepatocellular carcinoma resectable |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of neoadjuvant therapy with Nexavar, measured by changes of the CT perfusion blood flow from baseline to 12 weeks follow-up |
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E.2.2 | Secondary objectives of the trial |
To evaluate Diminishing amount of circulating tumour cells Changes in other CT perfusion parameters (blood volume, mean transit time, permeability surface area) Tumour response to sorafenib treatment according to modified RECIST criteria and to histopathology of explanted livers Percentage of patients reaching transplantation, thus avoiding dropout from waiting list Percentage of patients with radiographic tumour progression according to modified RECIST, while on waitinglist Impact of sorafenib on quality of life, assessed by EORTC QLQ C-30 and HCC-18 Impact of sorafenib treatment on liver function and toxicity while on waiting list. CTC v4.0 will used Postoperative 30-day morbidity and mortality after liver transplantation. Surgicla morbidity will be classified according to Clavien in a five grade scale. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients with HCC without prior medical anti-tumour therapy, basically eligible for LTx at screening. Tumour size according to the UCSF criteria are allowed.
HCC diagnosed by histology or according to non-invasive European Association for the study of the liver (EASL) criteria (only cirrhotic patients): 1. radiological criteria: two coinciding imaging techniques: Focal lesion >2 cm with arterial hypervascularization in a cirrhotic liver 2. Combined criteria: one imaging technique associated with alpha-fetoprotein (AFP): Focal lesion > 2 cm with arterial hypervascularization + AFP levels> 400 ng/ml
Pretreatment CT or MRI without evidence of radiographically definable vascular invation or extrahepatic disease, not older that 6 weeks
Sufficient hematologic, liver and renal function
PT-INR/PTT < 1,5 ULN
ECOG <2
No acute infections at time of therapy initiation
Written informed consent
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E.4 | Principal exclusion criteria |
Child-Pugh socre more than 7p at time of inclusion Expected waiting time for transplantation below three months Residual radiological definiable extrahepatic disease, portal vein involvement or lymph node involvement on CT, MRI or bone scan. Patients who are not potentially eligible for LTx are excluded Patients with prior or concomitant systemic anticancer therapy Patients with significant cardiovascular disease such as myocardial infarction, chronic heart failure or unstable coronary artery disease Patints with severe pulmonary disease that would be hazardous for LTx Uncontrolled hypertension, defined as systolic blood pressure >150 mg Hg or diastolic pressure >90 mm Hg, dispite optimal management Thrombotic or embolic events including transient ischemic attacks within the pas 6 months Patients with previous malignancy, within 5 years prior treatment, other then carcinoma in situ of the skin and the cervix. Previous HCC, treated locally with ablation or resection is permitted Patients <18 years Pregnant or breast-feeding patients. Both men and women must use adequate barrier birth control measures. Patients with uncontrolled infections or HIV sero-positive patients History or hypersensitivity to the investigational medicinal product Mental conditions rendering hte patient incapable to understand the nature, scope and consequences of the study No patient will be allowed to enroll in this study more than once Prior organ transplantation Concomitant immunosuppressive treatment Participation in other pharmaceutical clinical trials
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in CTp variable blood flow from baseline to 12 weeks follow-up.
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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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End of the trial is at last patient, last visit. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |