Clinical trial NCT01214343: Comparing Efficacy of Sorafenib Versus Sorafenib in Combination With Low-dose FP in Patients With Advanced HCC
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Advanced Hepatocellular Carcinoma
Carcinoma
Carcinoma, Hepatocellular
Liver Neoplasms
Neoplasms
Keywords: sorafenib
Hepatic intraarterial infusion chemotherapy
HAIC
Low dose FP
cisplatin
fluorouracil
Lead sponsor: Ministry of Health, Labour and Welfare, Japan
Sponsor class: OTHER_GOV
First posted: 2010-10-05
Enrollment: 190
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Overall survival
timeFrame: Overall survival is defined as the time from randomization to death due to any cause
Secondary outcomes:
measure: Time to progression
timeFrame: TTP is defined as the time from randomization to radiological progression.
measure: Progression Free Survival
timeFrame: PFS is defined as the time from randomization to radiological progression or death due to any cause
measure: Change of tumor marker
timeFrame: Every 4-6 weeks
measure: Biomarker predicting the efficacy
timeFrame: Pre and after treatment
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Kurume
country: Japan
facility: Kurume University Medical Center
state: Fukuoka
city: Ogaki
country: Japan
facility: Ogaki Municipal Hospital
state: Gifu
city: Sapporo
country: Japan
facility: Sapporo Medical University
state: Hokkaido
city: Sapporo
country: Japan
facility: Sapporo-Kosei General Hospital
state: Hokkaido
city: Takamatsu
country: Japan
facility: Japanese Red Cross Takamatsu Hospital
state: Kagawa
city: Tsu
country: Japan
facility: Mie University Hospital
state: Mie
city: Ohmura
country: Japan
facility: National Hospital Organization Nagasaki Medical Center
state: Nagasaki
city: Kurashiki
country: Japan
facility: Kawasaki Medical School Hospital
state: Okayama
city: Ikeda
country: Japan
facility: Ikeda Municipal Hospital
state: Osaka
city: Osaka-Sayama
country: Japan
facility: Kinki University Hospital
state: Osaka
city: Suita
country: Japan
facility: Osaka University Hospital
state: Osaka
city: Mitaka
country: Japan
facility: Kyorin University Hospital
state: Tokyo
city: Musashino
country: Japan
facility: Musashino Red Cross Hospital
state: Tokyo
city: Nerima
country: Japan
facility: Juntendo University Nerima Hospital
state: Tokyo
city: Ube
country: Japan
facility: Yamaguchi University Hospital
state: Yamaguchi
city: Chiba
country: Japan
facility: Chiba University Hospital
city: Gifu
country: Japan
facility: Gifu Municipal Hospital
city: Hiroshima
country: Japan
facility: Hiroshima City Hospital
city: Hiroshima
country: Japan
facility: Hiroshima University Hospital
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kyoto
country: Japan
facility: Kyoto University Hospital
city: Miyazaki
country: Japan
facility: Center for Gastroenterological and Hepatological Diseases
city: Niigata
country: Japan
facility: Saiseikai Niigata Dai-ni Hospital
city: Niigata
country: Japan
facility: Niigata University Medical and Dental Hospital
city: Okayama
country: Japan
facility: Okayama University Hospital
city: Osaka
country: Japan
facility: Osaka Red Cross Hospital
city: Tokushima
country: Japan
facility: The University of Tokushima Faculty of Medicine
city: Tokyo
country: Japan
facility: Kyoundo Hospital
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
Study officials:
affiliation: Kinki University Faculty of Medicine, Department of Gastroenterology and Hepatology
name: Masatoshi Kudo, Professor
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.