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

NCT ID: NCT01214343

Last Updated: 2011-06-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

190 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-31

Study Completion Date

2013-09-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Advanced Hepatocellular Carcinoma Carcinoma Carcinoma, Hepatocellular Liver Neoplasms Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Sorafenib with Low-dose FP

Group Type EXPERIMENTAL

Sorafenib with Low-dose FP

Intervention Type DRUG

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

Group Type ACTIVE_COMPARATOR

Sorafenib

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

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.

Intervention Type DRUG

Other Intervention Names

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Nexavar Low-dose FP Nexavar

Eligibility Criteria

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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.
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Ministry of Health, Labour and Welfare, Japan

OTHER_GOV

Sponsor Role lead

Responsible Party

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Kinki University Faculty of Medicine, Department of Gastroenterology and Hepatology

Principal Investigators

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Masatoshi Kudo, Professor

Role: STUDY_CHAIR

Kinki University Faculty of Medicine, Department of Gastroenterology and Hepatology

Locations

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Chiba University Hospital

Chiba, Chiba, Japan

Site Status RECRUITING

National Cancer Center Hospital East

Kashiwa, Chiba, Japan

Site Status RECRUITING

Kurume University Medical Center

Kurume, Fukuoka, Japan

Site Status RECRUITING

Gifu Municipal Hospital

Gifu, Gifu, Japan

Site Status RECRUITING

Ogaki Municipal Hospital

Ōgaki, Gifu, Japan

Site Status RECRUITING

Hiroshima City Hospital

Hiroshima, Hiroshima, Japan

Site Status RECRUITING

Hiroshima University Hospital

Hiroshima, Hiroshima, Japan

Site Status RECRUITING

Sapporo Medical University

Sapporo, Hokkaido, Japan

Site Status RECRUITING

Sapporo-Kosei General Hospital

Sapporo, Hokkaido, Japan

Site Status RECRUITING

Japanese Red Cross Takamatsu Hospital

Takamatsu, Kagawa-ken, Japan

Site Status RECRUITING

Kumamoto University Hospital

Kumamoto, Kumamoto, Japan

Site Status RECRUITING

Kyoto University Hospital

Kyoto, Kyoto, Japan

Site Status RECRUITING

Mie University Hospital

Tsu, Mie-ken, Japan

Site Status RECRUITING

Center for Gastroenterological and Hepatological Diseases

Miyazaki, Miyazaki, Japan

Site Status RECRUITING

National Hospital Organization Nagasaki Medical Center

Ohmura, Nagasaki, Japan

Site Status RECRUITING

Saiseikai Niigata Dai-ni Hospital

Niigata, Niigata, Japan

Site Status RECRUITING

Niigata University Medical and Dental Hospital

Niigata, Niigata, Japan

Site Status RECRUITING

Kawasaki Medical School Hospital

Kurashiki, Okayama-ken, Japan

Site Status RECRUITING

Okayama University Hospital

Okayama, Okayama-ken, Japan

Site Status RECRUITING

Ikeda Municipal Hospital

Ikeda, Osaka, Japan

Site Status RECRUITING

Osaka Red Cross Hospital

Osaka, Osaka, Japan

Site Status RECRUITING

Kinki University Hospital

Ōsaka-sayama, Osaka, Japan

Site Status RECRUITING

Osaka University Hospital

Suita, Osaka, Japan

Site Status RECRUITING

The University of Tokushima Faculty of Medicine

Tokushima, Tokushima, Japan

Site Status RECRUITING

Kyorin University Hospital

Mitaka, Tokyo, Japan

Site Status RECRUITING

Musashino Red Cross Hospital

Musashino, Tokyo, Japan

Site Status RECRUITING

Juntendo University Nerima Hospital

Nerima City, Tokyo, Japan

Site Status RECRUITING

Kyoundo Hospital

Tokyo, Tokyo, Japan

Site Status RECRUITING

National Cancer Center Hospital

Tokyo, Tokyo, Japan

Site Status RECRUITING

Yamaguchi University Hospital

Ube, Yamaguchi, Japan

Site Status RECRUITING

Countries

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Japan

Central Contacts

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Masatoshi Kudo, Professor

Role: CONTACT

+81-72-366-0221 ext. 3149

Kazuomi Ueshima, Dr

Role: CONTACT

+81-72-366-0221 ext. 3525

Facility Contacts

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Fumihiko Kanai, Dr.

Role: primary

Masafumi Ikeda, Dr.

Role: primary

Masatoshi Tanaka, Professor

Role: primary

Eiichi Tomita, Dr.

Role: primary

Takashi Kumada, Dr

Role: primary

Yoshiyuki Kobayashi, Dr.

Role: primary

Hiroshi Aikata, Dr.

Role: primary

Junji Kato, Dr.

Role: primary

Takumi Ohmura, Dr.

Role: primary

Chikara Ogawa, Dr.

Role: primary

Yutaka Sasaki, Professor

Role: primary

Etsuro Hatano, Professor

Role: primary

Katsuya Shiraki, Dr.

Role: primary

Hidemori Sakamoto, Dr.

Role: primary

Hiromi Ishibashi, Dr.

Role: primary

Toru Ishikawa, Dr.

Role: primary

Kouhei Akazawa

Role: primary

Keisuke Hino, Dr.

Role: primary

Kazuhide Yamamoto, Professor

Role: primary

Yasuharu Imai, Dr.

Role: primary

Ikuo Osaki, Dr.

Role: primary

Masatoshi Kudo, Professor

Role: primary

+81-72-366-0221 ext. 3149

Kazuomi Ueshima, Dr.

Role: backup

+81-72-366-0221 ext. 3525

Hiroaki Nagano, Professor

Role: primary

Tetsuji Takayama, Dr.

Role: primary

Junji Furuse, Professor

Role: primary

Namiki Izumi, Dr.

Role: primary

Shigehiro Kokubu, Dr.

Role: primary

Shuntaro Obi, Dr.

Role: primary

Takushi Okusaka, Dr.

Role: primary

Isao Sakaida, Prof

Role: primary

References

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Kudo M, Ueshima K, Yokosuka O, Ogasawara S, Obi S, Izumi N, Aikata H, Nagano H, Hatano E, Sasaki Y, Hino K, Kumada T, Yamamoto K, Imai Y, Iwadou S, Ogawa C, Okusaka T, Kanai F, Akazawa K, Yoshimura KI, Johnson P, Arai Y; SILIUS study group. Sorafenib plus low-dose cisplatin and fluorouracil hepatic arterial infusion chemotherapy versus sorafenib alone in patients with advanced hepatocellular carcinoma (SILIUS): a randomised, open label, phase 3 trial. Lancet Gastroenterol Hepatol. 2018 Jun;3(6):424-432. doi: 10.1016/S2468-1253(18)30078-5. Epub 2018 Apr 7.

Reference Type DERIVED
PMID: 29631810 (View on PubMed)

Ueshima K, Kudo M, Tanaka M, Kumada T, Chung H, Hagiwara S, Inoue T, Yada N, Kitai S. Phase I/II Study of Sorafenib in Combination with Hepatic Arterial Infusion Chemotherapy Using Low-Dose Cisplatin and 5-Fluorouracil. Liver Cancer. 2015 Dec;4(4):263-73. doi: 10.1159/000367751. Epub 2015 Oct 21.

Reference Type DERIVED
PMID: 26734580 (View on PubMed)

Other Identifiers

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SILIUS Phase III trial

Identifier Type: -

Identifier Source: org_study_id

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