E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hepatocellular carcinoma resectable |
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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 | 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 anti-tumor activity of sorafenib in tumor samples from patients with resectable hepatocellular carcinoma (HCC) |
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E.2.2 | Secondary objectives of the trial |
* To characterize pathologic findings in sorafenib pre-treated patients undergoing surgical resection for HCC. * To evaluate the number of R0 resections * To correlate pathological biomarkers changes in resected tumors after 4-week treatment with sorafenib in comparison with biopsies obtained prior to treatment. * To evaluate plasma biomarkers at baseline, Day 28 and the day before surgery. * To identify potential biomarkers of sensitivity and/or resistance on biological and pathological samples. * To characterize the safety profile of sorafenib in the study population. * To assess the tolerance of liver resection after sorafenib treatment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated informed consent. 2. Histological proven diagnosis of HCC. Patients with fibrolamellar or mixed histology are eligible. 3. Patient eligible for conservative hepatic resection, liver resection, with curative intent. 4. No cirrhosis or cirrhosis status with Child-Pugh score ≤ 7 (status A or B7). 5. Men or women of at least 18 years of age. 6. Body mass index between 18.5 and 30 kg/m2 (WHO normal range: 18.5 – 25). 7. Life expectancy ≥ 3 months. 8. Performance status 0 to 1 (ECOG). 9. Ability to swallow oral compound. 10. Patients must have adequate organ function including : - Haematologic: WBC > 3000, ANC > 1500, platelets ≥ 100,000, haemoglobin ≥ 9 g/dl. - Hepatic: Bilirubin < 1.5 X upper normal limit (UNL), aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatise (AP) ≤ 5 X UNL. - Renal: Serum creatinine < 2 X UNL - Prothrombin Time (PT) or international normalized ratio (INR) of PT, and partial thromboplastin time (PTT) < 1.5 X UNL; subjects receiving anti-coagulation therapy such as warfarin or heparin are allowed to participate if the coagulation parameters were within the above mentioned ranges prior to initiation of anticoagulant therapy. - Amylase and lipase < 1.5 X UNL. 11. Chronic liver disease without liver insufficiency and without portal liver hypertension. 12. For female patients of childbearing potential, negative pregnancy test within 7 days before starting the study drug. 13. Men and women are required to use adequate birth control during the study (when applicable). 14. Registration in a national health care system (CMU included).
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E.4 | Principal exclusion criteria |
1. Patient previous or candidate to orthotopic liver transplantation. 2. Any prior systemic or loco-regional treatment for HCC. 3. Cirrhotic status with Child-Pugh score > 7 (status B8-9 or C). 4. Any criterion for unresectability or medical condition that eventually contraindicates surgical resection at baseline evaluation. 5. Presence of any serious concomitant systemic disorders incompatible with the study, including uncontrolled hypertension, i.e. > 150/100 mmHg despite optimal therapy), or active uncontrolled infection, or active alcoholism. 6. Previous history of organ allograft or another malignancy (other than basal or squamous cell skin carcinoma or cured in situ cervical carcinoma) within 5 years of study entry. 7. Known history or presence of metastatic brain or meningeal tumors. Seizure disorder requiring medications such as anti-epileptics. 8. Concomitant treatment with full-dose anticoagulants (deep vein or catheter-associated thrombosis prophylaxis is permitted). 9. Cardiac arrhythmias requiring anti-arrhythmics (excluding beta-blockers or digoxin for chronic atrial fibrillation), active coronary artery disease or ischemia (myocardial infarction within the last 6 months), congestive heart failure > New York Heart Association (NYHA) Class II, pulmonary embolism or gastrointestinal bleeding during the 6 months prior to study entry. 10. Known history of human immunodeficiency virus (HIV) infection, or chronic hepatitis B or C. 11. Active clinically serious bacterial or fungal infections, i.e. grade 2 CTC [CTCAE] Version 3. 12. Any condition that is unstable or that could jeopardize the safety of the subject and his/her compliance with the study. Substance abuse or medical, psychological, or social conditions that could interfere with the subject’s adhesion to the study. 13. Known or suspected allergy to the investigational agent or to any agent given concomitantly. 14. Presence of asthenia or rash greater than CTC grade 1 at enrolment. 15. Treatment with any other investigational medicinal product within 28 days prior to study entry. 16. Chronic co-administration of CYP3A4 inducers such as rifampin, or millepertuis (hypericum perforatum), or phenytoin, or carbamazepine, or phenobarbital, or dexamethasone.
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
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 |
Biological study (biomarkers) |
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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
| 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 | 2 |
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 | 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 each patient, the participation will last approximately 4.5 months, i.e. a 1-week screening period, a 4-week treatment period, then the surgery procedure planned at one week after the end of the study treatment, and a follow-up period of 3 months. |
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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 | 0 |
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 |