Patients with advanced hepatocellular carcinoma only eligible for systemic treatment MedDRA version: 20.0 Level: SOC Classification code 10019805 Term: Hepatobiliary disorders System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Interventions
Trade Name: nexavar
Product Name: sorafenib
Product Code: [284461-73-0]
Pharmaceutical Form: Film-coated tablet
CAS Number: 284461-73-0
Current Sponsor code: sorafenib
Concentration unit: mg milligram
Sponsors
DIPARTIMENTO AD ATTIVITà INTEGRATA CHIRURGICO, MEDICO, ODONTOIATRICO E DI SCIENZE MORFOLOGICHE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Sorafenib: - Age > 18 years-old. - Child-Pugh class 5-6 (class A); - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2; - Patients who have a life expectancy of at least 12 weeks Child-Pugh class 5-6 (class A); - Patients with advanced HCC: i.e. patients not eligible for or who had disease progression after local-regional therapy; - Patients who have received local therapy;; - Patients with an adequate adequate hematologic function (platelet count, =60×109 per liter; hemoglobin, =8.5 g per deciliter; and prothrombin time international normalized ratio, =2.3; or prothrombin time, =6 seconds above control); - adequate hepatic function (albumin, =2.8 g per deciliter; total bilirubin, =3 mg per deciliter [51.3 µmol per liter]; and alanine aminotransferase and aspartate aminotransferase, =5 times the upper limit of the normal range); - adequate renal function (serum creatinine, =1.5 times the upper limit of the normal range); - Signed and dated IRB/IEC approved Informed Consent/Genetic Consent. Regorafenib - Age >18 years-old; - Child-Pugh class 5-6 (class A); - Patients with diagnosis of HCC, confirmed by histology according to AASLD/EASL criteria prior to the start of first-line therapy (sorafenib); - Patients with advanced HCC who had documented radiological progression during sorafenib as defined in a study-specific radiology charter. They must have tolerated sorafenib (=400 mg daily for at least 20 of the 28 days before discontinuation); - Patient must have at least one uni-dimensional measurable lesion by CT or MRI according to mRECIST which is either not previously treated by local therapy or, if treated, it has clearly progressed when the patient is recruited; - Patients who have a life expectancy of at least 12 weeks; - ECOG performance status of 0 or 1; - Patients who have received local therapy (such as surgery, radiation therapy, etc...) - Capability to swallow capsules intact (without chewing, crushing, or opening); Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: These exclusion criteria apply to both drugs: - Prior systemic therapy for HCC; - Active clinically serious infections (> grade 2 National Cancer Institute [NCI]-Common Terminology Criteria for Adverse Events [CTCAE] version 3.0); - Renal failure requiring hemo- or peritoneal dialysis; - History of cardiac disease: congestive heart failure > New York Heart Association (NYHA) class 2; active coronary artery disease (CAD); - Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta-blockers or digoxin, or uncontrolled hypertension; - Myocardial infarction less than 6 months prior to study entry; - Cholangiocarcinoma, hepatocholangiocarcinoma, fibrolamellar carcinoma and hepatoblastoma; - History of moderate or severe ascites, bleeding esophageal varices, hepatic encephalopathy or pleural effusions related to liver insufficiency within 6 months of screening; - Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS); - Known contraindications to sorafenib according to the drug prescribing information and/or severe hypersensitivity to sorafenib or any other component of sorafenib, or known intolerance to sorafenib.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective is to evaluate whether the different pharmacokinetics of the two drugs in males and females and the related pharmacogenetic variants of ADME (known to be different in male and female) are related to: - Different clinical response to Sorafenib (part 1) - Different clinical response to Regorafenib after failure of Sorafenib therapy (part 2);Secondary Objective: The secondary objectives of the study aim to evaluate whether gender-related outcomes, of therapy are also influenced by drug exposure (Cmin) and circulating biomarkers.(VEGF and VEGF-R, Angiopoietin-1 and Angiopoietin-2, NRP1, miRNA) chosen according with their relationship with TKI response For most of these biomarkers, demonstrable gender-related differences exist, not explored so far in relation with HCC and TKI inhibitors.;Primary end point(s): The study is divided in two consecutive parts (one primary endpoint each). Part 1 (sorafenib) The primary endpoint the progression free survival (PFS) to assess whether there are gender-related differences in the response to the therapy after initiation of sorafenib Part 2 (regorafenib) The primary endpoint of the Part 2 is overall survivals (OS) to assess whether there are gender-related differences in the response to the therapy after initiation of sorafenib, according to gender and ADME-related pharmacogenetic variants;Timepoint(s) of evaluation of this end point: Part 1: At disease progression, controlled with radiological imaging every 8 weeks Part 2: At the time of death of the patients or disease progression (disease progression, controlled with radiological imaging every 8 weeks) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Evaluation if the association between therapy outcomes ( in terms of PFS and OS) and gender are associated to different levels of circulating biomarkers and drug exposure (Cmin).;Timepoint(s) of evaluation of this end point: Consequently the achievement of primary endpoint (for both parts of the study) | — |
Countries
Italy
Contacts
Public ContactRicerca Indipendente AIFA
AIFA
Outcome results
None listed