E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatocellular carcinoma (HCC) non available for curative intent treatment |
Carcinome hépatocellulaire (CHC) non accessible à un traitement à visée curative |
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E.1.1.1 | Medical condition in easily understood language |
Randomized trial sorafenib-pravastative versus sorafenib alone for the palliative treatment of patients suffering from a liver cancer |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 evaluate the influence of pravastatine – sorafenib combination versus sorafenib alone on overall survival in patients with HCC developed with cirrhosis classified as Child-Pugh A and who cannot be treated by curative methods
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E.2.2 | Secondary objectives of the trial |
to evaluate the effect of the combination on progression free survival, time to progression, time to treatment failure and quality of life (QLQ-C30 and FACT HEP)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Hepatocellular carcinoma diagnosed:
-either histologically
-or, in cases where histological proof cannot be obtained (ascitis, coagulation disorders), the diagnosis may be done in cases of cirrhosis according to the 2005 EASL/AASLD criteria by demonstration of a focal hepatic lesion larger than 10 mm:
•by two dynamic imaging techniques (helicoïdal scan, MRI, ultrasound with contrast medium) for tumors smaller than 2 cm. The lesion must be characterized by hypervascularisation in the arterial time and a wash in the late portal time.
•by one dynamic imaging technique (helicoïdal scan, MRI, ultrasound with contrast medium) for tumors larger than 2 cm with hypervascularisation in the arterial time and a wash in the late portal time
•Patient not eligible for curative treatment (transplant, resection, percutaneous destruction) or chemo-embolisation or with HCC which is still progressing following the failure of specific treatment
•CLIP prognosis score 0 to 4
•Child-Pugh score A
•Transaminases activity ≤ 5 ULN and serum creatinine ≤ 1.5 ULN
•WHO performance status: 0, 1 or 2
•Over the age of 18 years
•Expected survival > 12 weeks
•Possibility for regular follow-up
•Written informed consent prior randomization |
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E.4 | Principal exclusion criteria |
•Extra-hepatic disease threatening the short- or medium-term vital prognosis
•Other cancerous pathology in progression, not including in situ cervical cancer, superficial bladder tumours and treated basal cell carcinoma. Any other cancer treated curatively more than 3 years previously can be included in the study
•Cardiac insufficiency (≥ NYHA class 2), uncontrolled arterial hypertension or arrhythmia, myocardial infarction less than 6 months previously
•Digestive haemorrhage less than 1 month
•Patients receiving or having previously received treatment with statins or sorafenib
•Pregnancy or lactation. Women at the age of procreation must use an acceptable method of contraception during the study and until 3 months after the end of the treatment. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Principal aim: to evaluate the influence of pravastatine – sorafenib combination versus sorafenib alone on overall survival in patients with HCC developed with cirrhosis classified as Child-Pugh A and who cannot be treated by curative methods. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Randomised study 1: 1. sorafenib-pravastatine versus sorafenib alone
Main hypothesis is to increase the median overall survival from 10 months with sorafenib alone to 13.5 months with sorafenib-pravastatine.
With a 2-sided bilateral 5% α error and a 20% error, an expected monthly accrual of 15 patients during 32 months and 5% drop-out rate, 474 patients will need to be enrolled to observe the 360 deaths required.
One interim analysis is planned when 50% of the required events have been observed to verify safety and efficacy of the combination. O’Brien – Fleming method.
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E.5.2 | Secondary end point(s) |
• Secondary aims: to evaluate the effect of the combination on progression free survival, time to progression, time to treatment failure and quality of life (QLQ-C30 and FACT HEP) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Randomised study 1: 1. sorafenib-pravastatine versus sorafenib alone
Main hypothesis is to increase the median overall survival from 10 months with sorafenib alone to 13.5 months with sorafenib-pravastatine.
With a 2-sided bilateral 5% α error and a 20% β error, an expected monthly accrual of 15 patients during 32 months and 5% drop-out rate, 474 patients will need to be enrolled to observe the 360 deaths required.
One interim analysis is planned when 50% of the required events have been observed to verify safety and efficacy of the combination. O’Brien – Fleming method.
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | 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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
SORAFENIB IN COMBINAISON WITH PRAVASTATINE VERSUS SORAFENIB ALONE |
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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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 103 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |