Advanced Hepatocellular CarcinomaPhase 3NCT01214343
Comparing Efficacy of Sorafenib Versus Sorafenib in Combination With Low-dose FP in Patients With Advanced HCC
A Phase 3 study testing Sorafenib with Low-dose FP and Sorafenib in people with Advanced Hepatocellular Carcinoma and Carcinoma, run by Ministry of Health, Labour and Welfare, Japan at 30 sites in Japan.
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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Advanced Hepatocellular Carcinoma, Carcinoma, Carcinoma, Hepatocellular
- What is being tested?
- Sorafenib with Low-dose FP and Sorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 190 participants
- Where
- 30 sitesJapan
- Study dates
- Oct 2010to Sep 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 20 Years and older.
- Life expectancy of at least 12 weeks at the pre-treatment evaluation.
- Advanced hepatocellular carcinoma with histological evidence on a biopsy specimen, or typical findings by dynamic CT or CT during hepatic arteriography/arterioportography.
- Not suitable for resection or local ablation therapy or transcatheter arterial chemoembolization.
- ECOG Performance status of 0 or 1.
- Cirrhotic status of Child-Pugh score ≤ 7.
Show all 16Show fewer
- 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
- Written Informed Consent must be obtained.
Who cannot join
- 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
- Renal failure
- 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
Show all 29Show fewer
- Serious hypertension
- Active clinically serious infections except for HBV and HCV
- Active chicken pox.
- Auditory disorder.
- Known history of HIV infection.
- Known metastatic or meningeal tumors.
- Extrahepatic tumor spread which affects patient's prognosis
- History of seizure disorder.
- Clinically significant gastrointestinal bleeding within 4 weeks prior to study entry.
- Embolization or infarction such as transient ischemic disease, deep vein thrombosis, pulmonary embolization.
- 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
- Patients unable to swallow oral medications.
- Gastrointestinal disease that may affect to the absorption of drug or pharmacokinetics.
- Medication that may affect to the absorption of drug or pharmacokinetics.
- Any disease or disorder that may affect the evaluation of study drug.
- Entry to the other clinical trial within 4 weeks prior to entry to this study.
- Pregnant or breast-feeding patients.
- Known allergy to the investigational agent or any agent given in association with this trial.
- 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.
- 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 locations and contacts
30 sites in 1 country.
30 sites in 1 country
Japan30 sites, 30 recruiting
- Recruiting
Chiba University Hospital
Chiba, Chiba, 260-8677
Fumihiko Kanai, Dr.
Fumihiko Kanai, Dr.
- Recruiting
Gifu Municipal Hospital
Gifu, Gifu, 500-8513
Eiichi Tomita, Dr.
Eiichi Tomita, Dr.
- Recruiting
Hiroshima City Hospital
Hiroshima, Hiroshima, 730-8518
Yoshiyuki Kobayashi, Dr.
Yoshiyuki Kobayashi, Dr.
- Recruiting
Hiroshima University Hospital
Hiroshima, Hiroshima, 734-8551
Hiroshi Aikata, Dr.
Hiroshi Aikata, Dr.
- Recruiting
Ikeda Municipal Hospital
Ikeda, Osaka, 563-8510
Yasuharu Imai, Dr.
Yasuharu Imai, Dr.
- Recruiting
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
Masafumi Ikeda, Dr.
Masafumi Ikeda, Dr.
- Recruiting
Kumamoto University Hospital
Kumamoto, Kumamoto, 860-8556
Yutaka Sasaki, Professor
Yutaka Sasaki, Professor
- Recruiting
Kawasaki Medical School Hospital
Kurashiki, Okayama-ken, 701-0192
Keisuke Hino, Dr.
Keisuke Hino, Dr.
- Recruiting
Kurume University Medical Center
Kurume, Fukuoka, 839-0863
Masatoshi Tanaka, Professor
Masatoshi Tanaka, Professor
- Recruiting
Kyoto University Hospital
Kyoto, Kyoto, 606-8507
Etsuro Hatano, Professor
Etsuro Hatano, Professor
- Recruiting
Kyorin University Hospital
Mitaka, Tokyo, 181-8611
Junji Furuse, Professor
Junji Furuse, Professor
- Recruiting
Center for Gastroenterological and Hepatological Diseases
Miyazaki, Miyazaki, 880-0003
Hidemori Sakamoto, Dr.
Hidemori Sakamoto, Dr.
- Recruiting
Musashino Red Cross Hospital
Musashino, Tokyo, 180-8610
Namiki Izumi, Dr.
Namiki Izumi, Dr.
- Recruiting
Juntendo University Nerima Hospital
Nerima City, Tokyo, 177-0033
Shigehiro Kokubu, Dr.
Shigehiro Kokubu, Dr.
- Recruiting
Saiseikai Niigata Dai-ni Hospital
Niigata, Niigata, 950-1104
Toru Ishikawa, Dr.
Toru Ishikawa, Dr.
- Recruiting
Niigata University Medical and Dental Hospital
Niigata, Niigata, 951-8520
Kouhei Akazawa
Kouhei Akazawa
- Recruiting
Ogaki Municipal Hospital
Ōgaki, Gifu, 503-8502
Takashi Kumada, Dr
Takashi Kumada, Dr.
- Recruiting
National Hospital Organization Nagasaki Medical Center
Ohmura, Nagasaki, 856-8562
Hiromi Ishibashi, Dr.
Hiromi Ishibashi, Dr.
- Recruiting
Okayama University Hospital
Okayama, Okayama-ken, 700-8558
Kazuhide Yamamoto, Professor
Kazuhide Yamamoto, Professor
- Recruiting
Osaka Red Cross Hospital
Osaka, Osaka, 543-8555
Ikuo Osaki, Dr.
Ikuo Osaki, Dr.
- Recruiting
Kinki University Hospital
Ōsaka-sayama, Osaka, 589-8511
Masatoshi Kudo, Professor, +81-72-366-0221 ext. 3149, m-kudo@med.kindai.ac.jp
Kazuomi Ueshima, Dr., +81-72-366-0221 ext. 3525, kaz-ues@med.kindai.ac.jp
- Recruiting
Sapporo Medical University
Sapporo, Hokkaido, 060-8556
Junji Kato, Dr.
Junji Kato, Dr.
- Recruiting
Sapporo-Kosei General Hospital
Sapporo, Hokkaido, 060-8556
Takumi Ohmura, Dr.
Takumi Ohmura, Dr.
- Recruiting
Osaka University Hospital
Suita, Osaka, 565-0871
Hiroaki Nagano, Professor
Hiroaki Nagano, Professor
- Recruiting
Japanese Red Cross Takamatsu Hospital
Takamatsu, Kagawa-ken, 760-0017
Chikara Ogawa, Dr.
Chikara Ogawa, Dr.
- Recruiting
The University of Tokushima Faculty of Medicine
Tokushima, Tokushima, 770-8503
Tetsuji Takayama, Dr.
Tetsuji Takayama, Dr.
- Recruiting
Kyoundo Hospital
Tokyo, Tokyo, 101-0062
Shuntaro Obi, Dr.
Shuntaro Obi, Dr.
- Recruiting
National Cancer Center Hospital
Tokyo, Tokyo, 104-0045
Takushi Okusaka, Dr.
Takushi Okusaka, Dr.
- Recruiting
Mie University Hospital
Tsu, Mie-ken, 514-8507
Katsuya Shiraki, Dr.
Katsuya Shiraki, Dr.
- Recruiting
Yamaguchi University Hospital
Ube, Yamaguchi, 755-8505
Isao Sakaida, Prof
Isao Sakaida, Professor
About this study
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
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.
Read the 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.
- Conditions
- Advanced Hepatocellular Carcinoma, Carcinoma, Carcinoma, Hepatocellular, Liver Neoplasms, Neoplasms
- Being tested
- Sorafenib with Low-dose FP, Sorafenib
- Keywords
- sorafenib, Hepatic intraarterial infusion chemotherapy, HAIC, Low dose FP, cisplatin, fluorouracil
- Medical subject headings
- Carcinoma, Carcinoma, Hepatocellular, Liver Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sorafenib with Low-dose FPDrug
Also called Nexavar, 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.
SorafenibDrug
Also called Nexavar
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.
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib with Low-dose FP | Experimental | Not described Receives: Drug: Sorafenib with Low-dose FP |
| Sorafenib | Active comparator | Not described Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival
Measured: Overall survival is defined as the time from randomization to death due to any cause
Secondary outcomes (4)
Time to progression
Measured: TTP is defined as the time from randomization to radiological progression.
Progression Free Survival
Measured: PFS is defined as the time from randomization to radiological progression or death due to any cause
Change of tumor marker
Measured: Every 4-6 weeks
Biomarker predicting the efficacy
Measured: Pre and after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2010 (estimated)
- Study startOct 2010
- Primary completionSep 2013 (estimated)
- Study completionSep 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Advanced Hepatocellular CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 190 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ministry of Health, Labour and Welfare, Japan
- Sponsor type
- Other government
- Investigators
- Masatoshi Kudo, Professor, Study chair, Kinki University Faculty of Medicine, Department of Gastroenterology and Hepatology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01214343
- Sponsor's protocol ID
- SILIUS Phase III trial
- Status last verified
- Oct 2010
- First submitted
- 4 Oct 2010
- Last updated
- 15 Jun 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 29631810Ueshima 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.
PubMed 26734580
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01214343
- Acronym / sponsor ID
- SILIUS Phase III trial
- Conditions
- Advanced Hepatocellular Carcinoma, Carcinoma, Carcinoma, Hepatocellular, Liver Neoplasms, Neoplasms
- Keywords
- sorafenib, Hepatic intraarterial infusion chemotherapy, HAIC, Low dose FP, cisplatin, fluorouracil
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 190 participants (estimated)
- Lead sponsor
- Ministry of Health, Labour and Welfare, JapanOther government
- Study start
- Oct 2010
- Primary completion
- Sep 2013 (estimated)
- Study completion
- Sep 2013 (estimated)
- First posted
- 5 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sorafenib with Low-dose FP | Experimental | Drug: Sorafenib with Low-dose FP |
| Sorafenib | Active comparator | Drug: Sorafenib |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 20 Years and older.
- Life expectancy of at least 12 weeks at the pre-treatment evaluation.
- Advanced hepatocellular carcinoma with histological evidence on a biopsy specimen, or typical findings by dynamic CT or CT during hepatic arteriography/arterioportography.
- Not suitable for resection or local ablation therapy or transcatheter arterial chemoembolization.
- ECOG Performance status of 0 or 1.
Key exclusion criteria (29 listed)
- 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
- Renal failure
- Any heart disease as follows
- Active clinically serious infections except for HBV and HCV
- Active chicken pox.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sorafenib with Low-dose FPAlso: Nexavar, Low-dose FPSorafenib 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. | Drug | Sorafenib with Low-dose FP |
| SorafenibAlso: NexavarSorafenib will be administered orally at a dose of 400 mg bid for 28 days in each cycle.A cycle is defined as 28 days. | Drug | Sorafenib |
Primary outcome
Overall survival
Time frame: Overall survival is defined as the time from randomization to death due to any cause
4 secondary outcomes
Time to progression
Time frame: TTP is defined as the time from randomization to radiological progression.
Progression Free Survival
Time frame: PFS is defined as the time from randomization to radiological progression or death due to any cause
Change of tumor marker
Time frame: Every 4-6 weeks
Biomarker predicting the efficacy
Time frame: Pre and after treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2011.
- Derived from this study: PubMed 29631810Kudo 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.
- Derived from this study: PubMed 26734580Ueshima 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Masatoshi Kudo, Professor study chair
Kinki University Faculty of Medicine, Department of Gastroenterology and Hepatology
30 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sorafenib with Low-dose FP and Sorafenib in people with Advanced Hepatocellular Carcinoma and Carcinoma, run by Ministry of Health, Labour and Welfare, Japan at 30 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 15 Jun 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Masatoshi Kudo, Professor (+81-72-366-0221 ext. 3149, m-kudo@med.kindai.ac.jp), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (time frame: Overall survival is defined as the time from randomization to death due to any cause). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01214343, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jun 2011.