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

Neoplasms Clinical Trial

Official title:

Randomized Controlled Trial Comparing Efficacy of Sorafenib Versus Sorafenib In Combination With Low Dose Cisplatin /Fluorouracil Hepatic Arterial InfUSion Chemotherapy in Patients With Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01214343
• Other study ID #: SILIUS Phase III trial
• Status: Recruiting
• Phase: Phase 3
• First received: October 4, 2010
• Last updated: June 14, 2011
• Start date: October 2010
• Est. completion date: September 2013

Study information

• Verified date: October 2010
• Source: Ministry of Health, Labour and Welfare, Japan
• Contact: Masatoshi Kudo, Professor
• Phone: +81-72-366-0221
• Email: m-kudo[@]med.kindai.ac.jp
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 190
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular
• Liver Neoplasms
• Neoplasms

Intervention

Drug:
• Sorafenib with Low-dose FP
Sorafenib will be administered orally at a dose of 400 mg bid for 28 days in a cycle. Cisplatin at the dose of 20 mg/m2 will be administered at day 1 and day8, and fluorouracil at the dose of 330 mg/m2 will be administered continuously at day 1-day 5, and day8-day12 via the implanted catheter system. A cycle is defined as 28 days.
• Sorafenib
Sorafenib will be administered orally at a dose of 400 mg bid for 28 days in each cycle.A cycle is defined as 28 days.

Locations

Country	Name	City	State
Japan	Chiba University Hospital	Chiba
Japan	Gifu Municipal Hospital	Gifu
Japan	Hiroshima City Hospital	Hiroshima
Japan	Hiroshima University Hospital	Hiroshima
Japan	Ikeda Municipal Hospital	Ikeda	Osaka
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Japan	Kumamoto University Hospital	Kumamoto
Japan	Kawasaki Medical School Hospital	Kurashiki	Okayama
Japan	Kurume University Medical Center	Kurume	Fukuoka
Japan	Kyoto University Hospital	Kyoto
Japan	Kyorin University Hospital	Mitaka	Tokyo
Japan	Center for Gastroenterological and Hepatological Diseases	Miyazaki
Japan	Musashino Red Cross Hospital	Musashino	Tokyo
Japan	Juntendo University Nerima Hospital	Nerima	Tokyo
Japan	Niigata University Medical and Dental Hospital	Niigata
Japan	Saiseikai Niigata Dai-ni Hospital	Niigata
Japan	Ogaki Municipal Hospital	Ogaki	Gifu
Japan	National Hospital Organization Nagasaki Medical Center	Ohmura	Nagasaki
Japan	Okayama University Hospital	Okayama
Japan	Osaka Red Cross Hospital	Osaka
Japan	Kinki University Hospital	Osaka-Sayama	Osaka
Japan	Sapporo Medical University	Sapporo	Hokkaido
Japan	Sapporo-Kosei General Hospital	Sapporo	Hokkaido
Japan	Osaka University Hospital	Suita	Osaka
Japan	Japanese Red Cross Takamatsu Hospital	Takamatsu	Kagawa
Japan	The University of Tokushima Faculty of Medicine	Tokushima
Japan	Kyoundo Hospital	Tokyo
Japan	National Cancer Center Hospital	Tokyo
Japan	Mie University Hospital	Tsu	Mie
Japan	Yamaguchi University Hospital	Ube	Yamaguchi

Sponsors (1)

Lead Sponsor	Collaborator
Ministry of Health, Labour and Welfare, Japan

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival		Overall survival is defined as the time from randomization to death due to any cause	No
Secondary	Time to progression		TTP is defined as the time from randomization to radiological progression.	No
Secondary	Progression Free Survival		PFS is defined as the time from randomization to radiological progression or death due to any cause	No
Secondary	Change of tumor marker		Every 4-6 weeks	No
Secondary	Biomarker predicting the efficacy		Pre and after treatment	No