Open-label phase II study of sorafenib in patients with advanced hepatocellular carcinoma (HCC) and Child Pugh score B with special analysis of patients 65 years or older - Sorafenib in Child Pugh Score B patients

• Conditions: hepatocellular carcinoma and Child Pugh score B; MedDRA version: 9.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectable

• Registration Number: EUCTR2008-008232-87-DE
• Lead Sponsor: Charite Universitätsmedizin Berlin- Campus Virchow-Klinikum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-03-09
• Last Update Posted: 10 December 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Subjects with proven HCC not suitable for loco-regional treatment options, resection or liver transplantation. Diagnosis of HCC can be made either histologically or according to EASL criteria.
2.Child-Pugh stage B
3.Age > 18 years
4.ECOG Performance Status of 0 to 2
5.Life expectancy of at least 12 weeks
6.Subjects with at least one uni-dimensional (for RECIST) measurable lesion. Lesions must be measured by MRI or CT
7.Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
- Hemoglobin > 9.0 g/dl
- Absolute neutrophil count (ANC) >1,500/mm3
- Platelet count ? 50,000/µl
- Total bilirubin < 3 times the upper limit of normal
- ALT and AST < 5 x upper limit of normal
- Alkaline phosphatase < 4 x upper limit of normal
- PT-INR/PTT < 1.5 x upper limit of normal
- Serum creatinine < 1.5 x upper limit of normal, creatinine clearance > 60 ml/min
8. Signed and dated informed consent before the start of specific protocol procedures

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Excluded medical conditions:
1.Child-Pugh stages A and C
2.Patients eligible for loco-regional treatment options, resection or transplantation
3.Patients with portal vein thrombosis exceeding thrombosis of a single intrahepatic branch
4.Patients with esophageal varices grade II (with high risk signs) or grade III without prior prophylactic band ligation
5.Acute variceal bleeding within the last 4 weeks
6.Ascites not adequately controlled by diuretic therapy
7.Encephalopathy > grade I
8.Uncontrolled arterial hypertension with systolic blood pressure >160 mmHg or diastolic blood pressure > 90 mm Hg despite optimal treatment
9.History of cardiac disease:
a)congestive heart failure > NYHA class 2;
b)active CAD (MI more than 6 mo prior to study entry is allowed);
c) cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted), or
d)uncontrolled hypertension (defined as blood pressure = 160 mmHg systolic and/or = 90 mmHg diastolic on medication)
10.History of HIV infection
11.Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
12.Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
13.Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
14.History of organ allograft.
15.Patients with evidence or history of bleeding diathesis
16.Serious non-healing wound, fracture, or ulcer
17.Major surgery within the last 4 weeks
18.Thrombotic or embolic events within the last 6 months
19.Patients undergoing renal dialysis
20.Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
21.Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial (and men for at least 3 months after last administration of study medication).
22.Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
23.Known severe hypersensitivity to sorafenib or any of the excipients
24.Patients unable to swallow oral medications.
25.Participation in another clinical study within 30 days of enrollment
26.Patients unable to give written informed consent
27.Patients that are placed in institutions by the order of a judge or other regulatory authority.

Excluded therapies and medications, previous and concomitant:
1.Anticancer chemotherapy or immunotherapy or targeted therapy (except study medication) during the study or within 4 weeks of study entry.
2.Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed).
3.Major surgery within 4 weeks of start of study
4.Autologous bone marrow transplant or stem cell rescue within 4 months of study
5.Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity suc

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the rate of patients with drug-related toxicity with NCI CTCAE grade = 3;Secondary Objective: –Time to progression (TTP)<br>–progression-free survival (PFS)<br>–response rate (EASL/RECIST)<br>–disease control rate (DCR: CR, PR or SD = 8 weeks as best overall response (BOR)) – EASL/RECIST<br>–Overall Survival (OS)<br>–Cumulative dose<br>–Average Daily Dose<br>–Quality of Life<br>–Safety<br>;Primary end point(s): Proportion of patients with drug-related toxicity with NCI CTCAE grade = 3 will be derived with the 95% confidence interval.<br>Furthermore all treatment-emergent and drug-related adverse events and serious AEs as well as safety laboratory parameters will be summarized by CTC grade<br>