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

Phase 3
Conditions
Liver Neoplasms
Carcinoma
Advanced Hepatocellular Carcinoma
Carcinoma, Hepatocellular
Neoplasms
Interventions
Registration Number
NCT01214343
Lead Sponsor
Ministry of Health, Labour and Welfare, Japan
Brief 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.

Detailed 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 & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
190
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Sorafenib with Low-dose FPSorafenib with Low-dose FP-
SorafenibSorafenib-
Primary Outcome Measures
NameTimeMethod
Overall survivalOverall survival is defined as the time from randomization to death due to any cause
Secondary Outcome Measures
NameTimeMethod
Biomarker predicting the efficacyPre and after treatment
Time to progressionTTP is defined as the time from randomization to radiological progression.
Progression Free SurvivalPFS is defined as the time from randomization to radiological progression or death due to any cause
Change of tumor markerEvery 4-6 weeks

Trial Locations

Locations (30)

Hiroshima City Hospital

🇯🇵

Hiroshima, Japan

Hiroshima University Hospital

🇯🇵

Hiroshima, Japan

National Cancer Center Hospital East

🇯🇵

Kashiwa, Chiba, Japan

Kurume University Medical Center

🇯🇵

Kurume, Fukuoka, Japan

Sapporo-Kosei General Hospital

🇯🇵

Sapporo, Hokkaido, Japan

Yamaguchi University Hospital

🇯🇵

Ube, Yamaguchi, Japan

Gifu Municipal Hospital

🇯🇵

Gifu, Japan

Kyoto University Hospital

🇯🇵

Kyoto, Japan

Saiseikai Niigata Dai-ni Hospital

🇯🇵

Niigata, Japan

Ogaki Municipal Hospital

🇯🇵

Ogaki, Gifu, Japan

National Hospital Organization Nagasaki Medical Center

🇯🇵

Ohmura, Nagasaki, Japan

Niigata University Medical and Dental Hospital

🇯🇵

Niigata, Japan

Osaka Red Cross Hospital

🇯🇵

Osaka, Japan

Kyoundo Hospital

🇯🇵

Tokyo, Japan

Japanese Red Cross Takamatsu Hospital

🇯🇵

Takamatsu, Kagawa, Japan

Sapporo Medical University

🇯🇵

Sapporo, Hokkaido, Japan

Mie University Hospital

🇯🇵

Tsu, Mie, Japan

Osaka University Hospital

🇯🇵

Suita, Osaka, Japan

Kumamoto University Hospital

🇯🇵

Kumamoto, Japan

Musashino Red Cross Hospital

🇯🇵

Musashino, Tokyo, Japan

Kawasaki Medical School Hospital

🇯🇵

Kurashiki, Okayama, Japan

Juntendo University Nerima Hospital

🇯🇵

Nerima, Tokyo, Japan

The University of Tokushima Faculty of Medicine

🇯🇵

Tokushima, Japan

Ikeda Municipal Hospital

🇯🇵

Ikeda, Osaka, Japan

Kinki University Hospital

🇯🇵

Osaka-Sayama, Osaka, Japan

Kyorin University Hospital

🇯🇵

Mitaka, Tokyo, Japan

Chiba University Hospital

🇯🇵

Chiba, Japan

Center for Gastroenterological and Hepatological Diseases

🇯🇵

Miyazaki, Japan

Okayama University Hospital

🇯🇵

Okayama, Japan

National Cancer Center Hospital

🇯🇵

Tokyo, Japan

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