E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatocellular Carcinoma, non-resectable |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 |
The principal objective of this study is to determine whether the addition of sorafenib to TransArterial ChemoEmbolisation (TACE) performed with doxorubicin eluting beads, prolongs progression free survival in patients with unresectable Hepatocellular Carcinoma compared to TACE alone. TACE is the standard treatment for patients with liver cancer that cannot be removed by surgery. This procedure involves blocking the blood vessel that supplies the tumour with small particles and killing it by starving it of oxygen. These particles can be loaded with the chemotherapy drug doxorubicin which is delivered directly to the tumour and may increase the effectiveness of the procedure. Sorafenib is a relatively new anti-cancer treatment which is approved for use in the treatment of liver cancer. It works by slowing down the growth of cancer cells and it also slows the rate of new vessel formation on which tumour growth depends. As they work in different and complementary ways, combining th |
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E.2.2 | Secondary objectives of the trial |
There are a number of secondary objectives in this study. As stated, the principal objective looks specifically at progression free survival which is defined as the interval between the date of randomisation and the date of progression or death from any cause. A secondary objective of this study is to determine whether the combination therapy prolongs either the time to progression alone or the overall survival of patients. Both factors are of important significance but would require a larger sample size to form the principal objective. A realistically achievable recruitment target is crucial to a successful study and progression free survival was considered to be a suitable surrogate. The study will also assess whether the combination therapy has acceptable toxicity, the affect on disease response and the impact on patient Quality of Life. The study will measure whether it reduces the frequency for repeat TACE as measured by the number of TACE procedures performed in 12 months f |
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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 |
Translational and Quality of Life (QoL) sub-studies are being proposed. The translational substudy will be for proteomic and genomic analysis. Research will be on liver tissue taken at diagnosis and blood samples obtained before and during the study. The QoL substudy will assess general & hepatocellular specific aspects of quality of life using EORTC QLQ-C30 version 3, EORTC QLQ-HCC18 & EuroQoL (EQ-5D) questionnaire. |
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E.3 | Principal inclusion criteria |
Inclusion Criteria • Histological or cytological diagnosis or meet the AASLD criteria for diagnosis of HCC and at least one uni-dimensional lesion measurable according to the RECIST criteria by CT-scan or MRI. • Not a candidate for surgical resection • Aged ≥ 18 years and estimated life expectancy >3 months • ECOG performance status ≤ 1 • Adequate haematological function Hb ≥ 9g/L, absolute neutrophil count ≥1.5x109/L, platelet count ≥ 60x109/L • Bilirubin ≤ 50 µmol/L, AST and ALT ≤ 5 x ULN, ALP < 4 x ULN • Adequate renal function; Creatinine ≤ 1.5 x ULN • INR ≤ 1.5 • Amylase < 2 x ULN • Child-Pugh A (score ≤ 6) • Left Ventricular Ejection Fraction ≥ 45% • Women of child-bearing potential should have a negative pregnancy test prior to study entry. Both men and women must be using an adequate contraception method, which must be continued for 3 months after completion of treatment • Written informed consent |
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E.4 | Principal exclusion criteria |
• Extrahepatic metastasis • Prior embolisation, systemic or radiation therapy for HCC • Any contraindications for hepatic embolisation procedures procedures including portosystemic shunt, hepatofugal blood flow, known severe atheromatosis. • Investigational therapy or major surgery within 4 weeks of trial entry • Any ablative therapy (RFA or PEI ) for HCC (this should not exclude patients if target lesion(s) have not been treated and occurred >6 weeks prior study entry) • History of bleeding within the past 4 weeks • Child-Pugh cirrhosis C or B (score <7) • Hepatic encephalopathy • Ascites refractory to diuretic therapy • Documented occlusion of the hepatic artery or main portal vein • Hypersensitivity to intravenous contrast agents • Active clinically serious infection > Grade 2 NCI-CTC version 4 • Pregnant or lactating women • Known history of HIV infection • History of second malignancy except those treated with curative intent more than three years preciously without relapse and non-melanotic skin cancer or cervical carcinoma in situ • Evidence of severe or uncontrolled systemic diseases, cardiac arrhythmias (requiring anti-arrhythmic therapy or pace maker), uncontrolled hypertension, congestive cardiac failure >NYHA class 2, MI within 6 months or laboratory finding that in the view of the Investigator makes it undesirable for the patient to participate in the trial • Psychiatric or other disorder likely to impact on informed consent • Patient is unable and/or unwilling to comply with treatment and study instructions • Patient unable to swallow oral medications |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression Free Survival |
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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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
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 | Yes |
E.8.2.3 | Other | No |
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 | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 | 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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For regulatory and ethical purposes, the trial will be closed to recruitment when 206 patients have been recruited to each treatment arm. The study will continue for one year after the last patient has been recruited. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
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 |