Phase II study evaluating transarterial chemoembolization (TACE) in combination with sorafenib for the treatment of advanced hepatocellular carcinoma (HCC) - TACE and sorafenib for HCC

• Conditions: histologically proven advanced hepatocellular carcinoma (HCC) not suitable for resection or liver transplantation but without extrahepatic manifestations and without previous treatment for HCC; MedDRA version: 9.1Level: LLTClassification code 10019828Term: Hepatocellular carcinoma non-resectable

• Registration Number: EUCTR2007-000730-40-DE
• Lead Sponsor: Heinrich-Heine-Universität Düsseldorf

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-05-10
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

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

Inclusion Criteria

– Patients with histologically confirmed HCC not suitable for resection or liver transplantation (> 3 tumors > 3 cm; one tumor > 5 cm; vascular invasion; corresponding to intermediate stage according to the BCLC staging criteria)
– Age >= 18 years
–Patients with measurable disease according to RECIST
– Performance status ECOG 0-2
– Patients naive to treatment with respect to the HCC
– Normal organ and bone marrow function defined as:
– Hematopoetic: absolute neutrophil count > 1,500/mm3, platelet count > 100,000/mm3, hemoglobin > 9g/dL
– INR < 1.5 ULN and PTT within normal limits
– Hepatic: AST or ALT < 5 x ULN, alkaline phosphatase < 4 x ULN
– Renal: serum creatinine < 1.5 x ULN
– Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
– Male or female patients with reproductive potential must use an approved contraceptive method during and for 3 months after the end of treatment with study medication (Approved methods for women are oral contraceptives with estrogen and progesterone, vaginal rings, contraceptive patches, estrogen-free ovulation inhibitors, intrauterine devices with progesterone, 3-month injections with depot progesterone, implants settting free progesterone, abstinence or sterilization (vasectomy) of the male partner. Men must use condomes.)
– Written informed consent (including consent to data reporting)
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

– Patient is eligible for liver resection or liver transplantation
– Extrahepatic tumor manifestation
– Thrombosis of the portal vein
– > 8 points according to Child Pugh classification
– Prior TACE or RFTA or any other local ablative treatment
– Prior systemic anticancer chemotherapy or radiotherapy for HCC
– Total bilirubin > 4.5 mg/dl
– Life expectancy of less than 12 weeks
– Esophageal varices grade III (any) or esophageal varices grade II with increased risk for bleeding (red wale signs, cherry spots, red coloration, hematocystic spots) without prophylactic band ligation
– Cardiac disease: congestive heart failure > class II NYHA, unstable angina or new onset of angina or myocardial infarction within the past 6 months. Cardiac ventricular arrhythmias requiring antiarrhythmic therapy
– Uncontrolled hypertension defined as systolic blood pressure > 150 mm Hg or diastolic pressure > 90 mm Hg, despite optimal management
– Known or suspected hyperthyroid state
– Known brain metastasis. Patients with symptoms should undergo CT/MRT of the brain to exclude brain metastasis
– Patients with seizure disorder requiring medication (such as steroids or antiepileptics)
– History of organ allograft
– Active clinically serious infections > CTCAE grade 2
– Thrombotic or embolic events including transient ischemic attacks within the past 6 months
– Hemorrhage/bleeding event >= CTCAE grade 3 within 4 weeks of first dose of study drug
– Acute variceal bleeding within the last 2 weeks
– Serious non healing wound, ulcer or bone fracture
– Evidence or history of bleeding diathesis or coagulopathy
– Therapeutic anticoagulation with vitamin K antagonists such as warfarin, or with heparins or heparinoids. Low dose warfarin is permitted if INR is < 1.5. Low dose aspirin is permitted (<= 100 mg/day)
– Chronic daily treatment with aspirin > 100 mg/day
– Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
– Known or suspected allergies to sorafenib, anthracyclines (including doxorubicin) or lipiodol (containing esters of iodinated fatty acids of poppy oil) or any agent given in the course of this trial
– Contraindications to the use of sorafenib, doxorubicin or lipiodol as mentioned in the current summary of product characteristics
– Previous cancer that is distinct in primary site or histology from HCC except cervical cancer in situ, treated basal cell carcinoma, superficial bladder tumors or any cancer curatively treated 3 years prior to study entry
– Substance abuse, medical or psychological condition that may interfere with the patient´s participation in the study
– Participation in another clinical trial with any investigational study drug (whatever the use, curative, prophylactic or diagnostic intent) within 30 days prior to enrollment
– Incapability to give valid informed consent (including patients who are dependent on the sponsor or the investigator)
– Lactating women

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary objective:<br>– determination of time to progression (TTP)<br>;Secondary Objective: Secondary objectives:<br>determination of<br>– overall survival (OS)<br>– disease control rate (DCR: CR, PR or SD as best overall response (BOR))<br>– progression-free survival (PFS)<br>– total number of TACE cycles<br>– safety profile<br>;Primary end point(s): Progression of HCC or patient´s death