Comparing Efficacy of Sorafenib Versus Sorafenib in Combination With Low-dose FP in Patients With Advanced HCC

Ministry of Health, Labour and Welfare, Japan

Status and phase: Unknown; Phase 3

Conditions: Carcinoma, Hepatocellular; Neoplasms; Liver Neoplasms; Carcinoma; Advanced Hepatocellular Carcinoma

Treatments: Drug: Sorafenib; Drug: Sorafenib with Low-dose FP

Study type: Interventional

Funder types: Other

Identifiers

NCT01214343

SILIUS Phase III trial

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy of sorafenib in combination with low dose cisplatin /fluorouracil hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma.

Full description

Sorafenib with Low-dose FP Group

Sorafenib will be administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid) for 28 days. Cisplatin at the dose of 20mg/m2 will be administered at day 1 and day8, and fluorouracil at the dose of 330mg/m2 will be administered continuously at day1-day5, and day8-day12 via the implanted catheter system.

Sorafenib Group

Sorafenib will be administered orally at a dose of 400 mg (2 x 200 mg tablets) twice daily (bid) for 28 days.

The treatment regimen will be continued until radiographic or symptomatic progression, the development of unacceptable toxicity.

Enrollment: 190 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. 20 Years and older.

2. Life expectancy of at least 12 weeks at the pre-treatment evaluation.

3. Advanced hepatocellular carcinoma with histological evidence on a biopsy specimen, or typical findings by dynamic CT or CT during hepatic arteriography/arterioportography.

4. Not suitable for resection or local ablation therapy or transcatheter arterial chemoembolization.

5. ECOG Performance status of 0 or 1.

6. Cirrhotic status of Child-Pugh score ≤ 7.

7. Adequate bone marrow, liver and renal function, as assessed by the following laboratory requirements:

   • Hemoglobin ≥8.5 g/dl
   • Granulocytes≥1500/μL
   • Platelet count ≥50,000 /μL
   • PT-INR ≤ 2.3
   • Total serum bilirubin ≤ 2 mg/dl
   • AST(SGOT) and ALT(SGPT) ≤ 6 × upper limit of normal
   • Serum creatinine ≤ 1.5 × upper limit of normal
   • Amylase ≤ 2 × upper limit of normal

8. Written Informed Consent must be obtained.

Exclusion criteria

1. Previous malignancy (except for cervical carcinoma in situ, adequate treated basal cell carcinoma, or superficial bladder tumors [Ta, Tis and T1], early gastric cancer, or other malignancies curatively treated > 3 years prior to entry

2. Renal failure

3. Any heart disease as follows

   • Congestive heart failure defined as NYHA class III or IV
   • Active coronary artery disease or ischemic heart disease such as cardiac infarction within 6 months prior to screening
   • Serious cardiac arrhythmia
   • Serious hypertension

4. Active clinically serious infections except for HBV and HCV

5. Active chicken pox.

6. Auditory disorder.

7. Known history of HIV infection.

8. Known metastatic or meningeal tumors.

9. Extrahepatic tumor spread which affects patient's prognosis

10. History of seizure disorder.

11. Clinically significant gastrointestinal bleeding within 4 weeks prior to study entry.

12. Embolization or infarction such as transient ischemic disease, deep vein thrombosis, pulmonary embolization.

13. Any history of treatment as follows:

    • Treatment with the agent which induces CYP3A4
    • Surgical procedure within 4 weeks prior to start of study drug
    • History of organ allograft

14. Patients unable to swallow oral medications.

15. Gastrointestinal disease that may affect to the absorption of drug or pharmacokinetics.

16. Medication that may affect to the absorption of drug or pharmacokinetics.

17. Any disease or disorder that may affect the evaluation of study drug.

18. Entry to the other clinical trial within 4 weeks prior to entry to this study.

19. Pregnant or breast-feeding patients.

20. Known allergy to the investigational agent or any agent given in association with this trial.

21. Substance abuse, medical, psychological or social conditions that, in the judgment of the investigator, is likely to interfere with the patient's participation in the study or evaluation of the stuy results.

22. Any condition that is unstable or could jeopardize the safety of the patient and its compliance in the study, in the investigator's judgment.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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190 participants in 2 patient groups

Sorafenib with Low-dose FP

Experimental group

Treatment:

Drug: Sorafenib with Low-dose FP

Sorafenib

Active Comparator group

Treatment:

Drug: Sorafenib