Intermittent treatment with sorafenib in combination with transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): a randomized open-label phase 2 study
- Conditions
- C22.0Liver cell carcinoma
- Registration Number
- DRKS00012551
- Lead Sponsor
- Dekanat des Fachbereichs Medizin Klinikum der Johann Wolfgang Goethe-Universität, Haus 1
- Brief Summary
see attached CSR
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 54
Written informed consent granted prior to initiation of any study specific screening procedures
– Patients with histologically confirmed HCC not suitable for resection or liver transplantation (> 3 tumors > 3 cm; one tumor > 5 cm). Vascular invasion is allowed as long as the main trunk of the portal vein is not invaded)
– Absence of extrahepatic spread
– Age > 18 years
– Patients with measurable disease according to RECIST
– Performance status ECOG 0 and 1 (Appendix 20)
– 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 > 60,000/mm3, hemoglobin > 9g/dL
– INR < 1.5 ULN
– Hepatic: AST or ALT < 5 x ULN, bilirubin = 3 mg/dl
– Renal: serum creatinine < 1.5 x ULN
– Child-Pugh stage A
– Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the randomization
– Male or female patients of child-bearing potential must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received
Extrahepatic tumor manifestation
– Thrombosis of the main portal vein (thrombosis of a side-branch is allowed)
– Child Pugh status B or C > 6 points according to Child Pugh classification
– Prior TACE or selective intraarterial Radiotherapiy (SIRT)
– Prior systemic anticancer chemotherapy for HCC
– 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 except chronic hepatitis C infection
– Thrombotic or embolic events including transient ischemic attacks within the past 6 months
– Hemorrhage or 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 Marcumar, heparins or indirect factor-Xa inhibitors or direct thrombinantagonists. Low dose aspirin is permitted (100 mg per day)
– Major surgery, open biopsy or significant traumatic injury within 4 weeks of first dose of study drug
– Known or suspected allergies to sorafenib, mitomycin C or lipiodol
– 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)
– Pregnancy and breast-feeding women
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method determination of time to progression (TTP) by mRECIST for HCC
- Secondary Outcome Measures
Name Time Method Determination of<br>– overall survival (OS)<br>– response rate (either complete response, CR, or partial response, as measured by mRECIST for HCC)<br>– safety profile<br>– quality of life (as measured by FACT-Hep and EQ-5D questionaires