Efficacy and Safety of Concurrent TACE and Sorafenib in Patients With HCC and Extrahepatic Metastasis (COTSOM Study)

• Status: Unknown status
• Trial end date: 2018-06-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is a phase II, prospective, open-label, single arm, single center study of the efficacy and safety of concurrent conventional transarterial chemoembolization (TACE) and sorafenib in patients with hepatocellular carcinoma and extrahepatic metastasis. All of the 55 patients with hepatocellular carcinoma and newly diagnosed extrahepatic (lung, bone, lymph node, adrenal gland) metastasis will be included.

On demand conventional TACE will be performed in all the patients after enrollment and can be continued until intrahepatic CR, TACE failure or consent withdrawal. Sorafenib will be started 3-7 days after the first and each subsequent TACE and stopped one day before next TACE and will be continued until sorafenib failure, consent withdrawal or condition worsening by clinical decision. Repeated on-demand TACE and sorafenib should continue until the criteria for treatment discontinuation are met. After initiation of sorafenib combination treatment, patients will be seen and will perform routine examination at week 4 and, after then routine examination will be followed every 6 ± 2 weeks.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Asan Medical Center
• Collaborator: Bayer
• Treatments: Chlorotrianisene; Niacinamide; Sorafenib

Criteria

Inclusion Criteria:

• Patients with HCC and newly diagnosed extrahepatic metastasis meeting of following criteria

1. Clinical or histological diagnosis of HCC based on the guidelines: Early enhancement followed by late wash-out on dynamic liver imaging (CT or MRI) Or Pathological examination of liver biopsy

2. Evidence of extrahepatic metastasis with any of following methods; CT, MRI, bone scan, positron emission tomography with FDG-PET, biopsy of metastatic lesion

3. Preserved liver function classified as Child-Pugh A

4. ECOG PS of 0-1

5. Age of at least 20 years

6. Patients is able to comply with scheduled visits, evaluation plan, and other study procedures

7. Patient is willing to provide written informed consent

8. There is no limitation of prior TACE session number in case that further TACE is still considered to be beneficial

9. Women of childbearing potential must have a negative pregnancy test performed within 14 days of the start of treatment. All patients of child-bearing potential must use adequate birth control measures during the course of the trial (barrier method of birth control) and up to at least 30 days of last dose.

Exclusion Criteria:

• Presence of any of following criteria

1. Patients who are diagnosed as not eligible for further TACE before screening

2. Patients with advanced liver disease as defined below:

• Child Pugh B and C

• Encephalopathy

• Ascites

3. Complete occlusion of main portal vein (PV) by HCC

4. Patients with brain metastasis

5. Inadequate liver function that could not perform TACE:

• AST > 5 X ULN(upper limit normal) or ALT > 5 X ULN

• Total bilirubin > 2.0 mg/dL

• Prothrombin time INR > 1.7

6. Inadequate bone marrow function (absolute neutrophil count < 1,500/μL, Hemoglobin (Hgb) < 8 g/dL, platelet count < 50,000/μL)

7. Inadequate renal function (creatinine > 1.5 x ULN)

8. Treatment with previous local therapy such as resection of HCC, radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) < 4 weeks prior to the screening

9. Prior sorafenib use

10. Investigational drugs or other molecular target drugs ongoing or completed < 4 weeks prior to the screening

11. Clinically significant gastrointestinal bleeding within 4 weeks prior to start of study drug

12. Uncontrolled bleeding varices.

13. History of cardiac disease:

• Congestive heart failure >NYHA class 2

• Active coronary artery disease (CAD) (myocardial infarction more than 6 months prior to study entry is allowed)

• Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before screening

• Cardiac arrhythmias which are poorly controlled with anti-arrhythmic therapy or requiring pace maker

• Uncontrolled hypertension

14. Active clinically serious infections except for HBV and HCV infection

15. Patients with HIV

16. Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks) within 6 months before screening

17. Recently treated or concurrent cancer that has a primary site or histology distinct from HCC except any cancer curatively treated more than 3 years prior to screening

18. Pregnant or breast-feeding subjects

19. Major surgery, open biopsy, or significant traumatic injury 4 weeks before screening

20. Presence of a non-healing wound, non-healing ulcer, or bone fracture

21. Subjects who have used strong CYP3A4 inducers within 4 weeks before screening

22. Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial

23. Any other condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment or could interfere with the completing the study