Advanced stage hepatocellular carcinoma (stage C of BCLC classification) MedDRA version: 14.1 Level: LLT Classification code 10019828 Term: Hepatocellular carcinoma non-resectable System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Nexavar
Product Name: Sorafenib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: SORAFENIB TOSILATE
CAS Number: 475207-59-1
Current Sponsor code: 475207-59-1
Other descriptive name:
Sponsors
JOSE LUIS MONTERO ALVAREZ
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patient older than 18 years old. 2. Diagnosis of advanced HCC according to the AASLD Guidelines. 3. HCC stage B with contraindication to transarterial chemoembolization (TACE) or stage C according to Barcelona Clinic Liver Cancer (BCLC) staging classification. 4. Sorafenib treatment-naive patient. 5. Child-Pugh class A (5-6 points) or class B (7 points), without ascites (mild ascites controlled with diuretics is allowed) and encephalopathy. Child-Pugh status must be calculated based on clinical findings and laboratory results during 30 days before inclusion in the study. 6. ECOG Performance Status lower than 2. 7. Adequate liver, renal and bone marrow function as shown by: AST y ALT lower than 5 x ULN (upper limit of normal); bilirubin lower than 2 mg/dL; INR lower than 2; absolute neutrophil count (ANC) higher than 1.2 x 103 per ml ; platelets higher than 70 x 103 per ml ; serum creatinine lower than 1.5 mg/dL. 8. Written informed consent. 9. Women of chilbearing potential (WOCBP) must have a negative serum pregnancy test performed in the screening visit. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilizatiion (hysterectomy, bilateral tubal ligation or bolateral oophorectomy) or is not postmenopausal. Post menopause is defined as an amenorrhea state longer than 12 consecutive months. 10. Men and women enrolled in this trial must used adequate barrier bith control measure since two weeks prior to the start of investigational product, during the course of the trial and two weeks after the last dose of investigational product. 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 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 66
Exclusion criteria
Exclusion criteria: 1. Prior liver transplantation. 2. Known history of HIV infection. 3. Previous/concurrent cancer (distinct from HCC) known during the last 3 years, except for cervical carcinoma in situ, basal cells carcinoma and superficial bladder tumors. 4. History of cardiovascular disease: - uncontrolled hypertension, defined as systolic blood pressure higher than 150 mmHg or diastolic pressure higher than 90 mmHg despite optimal medical management. - active coronary disease, unstable or newly diagnosed angina or myocardial infarction less than 12 months prior to study entry. - cardiac arrhythmias requiring anti-arrhytmic therapy other than beta blockers or digoxin. - congestive heart failure higher than NYHA class 2. 5. Subjects with history of bleeding diathesis. 6. History of gastrointestinal bleeding within 30 days of randomizaion. 7. Subjects with a history of esophageal varices bleeding without efffective therapy and/or treatment to prevent bleeding recurrence. 8. Abuse to drugs, clinical or psychological states that might interfere in the participation or evaluation of study results. 9. Subjects on warfarin, acenocumarol, fenprocumone. 10.Female patients who are pregnant or breast feeding. 11.Unable or unwilling subjects to give informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine efficacy of Sorafenib in advanced hepatocellular carcinoma (stage C of BCLC classification) after radiological progression.;Secondary Objective: -To determine safety of Sorafenib in advanced hepatocellular carcinoma (stage C of BCLC classification) after radiological progression. -To assess quality of life. -To evaluate adherence to Sorafenib treatment. ADDITIONAL EXPLORATORY OBJECTIVE: To determine if growth factors related to neoangiogenesis, as EGF,FGF-2,VEGF and PDGF, could be biomarkers of respond to Sorafenib treatment in advanced hepatocellular carcinoma.;Primary end point(s): Overall Survival (OS);Timepoint(s) of evaluation of this end point: At the end of the clinical trial | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Safety Variables. All subjects who receive at least one dose of Sorafenib will be valid for safety analysis. - Adverse Events (AEs): according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 of National Cancer Institute (NCI). All adverse events occurring after the subject included in the study until 30 days last treatment just as adverse event causality relationship with study drug, must be recorded in the subject?s clinical informs and subject?s case record form. The intensity or severity of adverse event should be documented using the NCI-CTCAE; version 3.0.If CTCAE grading does not exist for an AE, the severity of mild, moderate, severe and life-threatening, or grades 1-4, will be used. - Safety assessments: Results of blood test (hematology, serum chemistry, coagulation tests), vital signs data (heart rate, blood pressure, respiration rate and body temperature), weight, 12-lead electrocardiogram (ECG) and physical examinations. 2. - Adherence to treatment. Drug Accountability: Sorafenib tablets accountability and the patient?s information in terms of lost of forgotten doses will be recorded in the subject?s clinical informs at each study visit. 3. - Quality of life. Patient Questionnaires: the patient reports outcomes through EQ-5D questionnaire (or EuroQol Questionnaire: a generic utility measure used to characterize current health states) and FACT-Hep questionnaire (The Functional Assessment of Cancer Therapy- Hepatobiliary Questionnaire: measuring health-related quality of life in patients with hepatobiliary cancers). Exploratory Variable: Determine serological levels of growth factor related to neoangiogenesis, as EGF, FGF-2,VEGF and PDGF, by Bioplex technology.;Timepoint(s) of evaluation of this end point: At the end of study | — |
Countries
Spain
Contacts
Public ContactCLINICAL UNIT OF DIGESTIVE SYSTEM
REINA SOFIA UNIVERSITARY HOSPITAL
Outcome results
None listed