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Study of Sorafenib In Combination With Low-dose 5-fluorouracil/Cisplatin (FP) Intraarterial Infusion Chemotherapy (SILIUS)

This study has been completed.
Sponsor:
Information provided by:
Japan Liver Oncology Group
ClinicalTrials.gov Identifier:
NCT00933816
First received: July 1, 2009
Last updated: November 24, 2010
Last verified: November 2010
  Purpose

The purpose of this study is to determine the recommended dose of the combination therapy of sorafenib with hepatic arterial infusion of low dose cisplatin and fluorouracil on patients with advanced hepatocellular carcinoma (Phase I), and to evaluate the efficacy of this combination therapy in the recommended dose (Phase II).


Condition Intervention Phase
Hepatocellular Carcinoma
Drug: sorafenib, cisplatin, fluorouracil
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Sorafenib In Combination With Low-dose FP Intraarterial Infusion Chemotherapy

Resource links provided by NLM:


Further study details as provided by Japan Liver Oncology Group:

Primary Outcome Measures:
  • Dose limiting toxicity in phase I and Time to progression in Phase II [ Time Frame: Every 4 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Phase I and II: Overall survival (OS) [ Time Frame: Every day ] [ Designated as safety issue: Yes ]
  • Phase I and II: Progression free survival (PFS) [ Time Frame: Every four weeks ] [ Designated as safety issue: Yes ]
  • Phase I: Time to progression (TTP) [ Time Frame: Every four weeks ] [ Designated as safety issue: Yes ]
  • Phase I and II: Response Rate (RR) [ Time Frame: Every four weeks ] [ Designated as safety issue: Yes ]
  • Phase I and II: Adverse effect (AE) [ Time Frame: Every four weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 37
Study Start Date: July 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sorafenib with Low-dose FP Drug: sorafenib, cisplatin, fluorouracil
Sorafenib will be administered orally at a dose of 400 mg bid for 28 days in the all patients. Cisplatin at the dose of 10-20 mg/m2 will be administered at day 1 and day8, and fluorouracil at the dose of 170-330 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 and 3 cycles of this combination therapy will be continued.
Other Name: sorafenib with hepatic arterial infusion of low dose FP

Detailed Description:

In Phase I, there will be 9 to 18 patients enrolled. Cohorts of 3 to 6 patients will receive escalated dose of cisplatin and fluorouracil until the MTD is reached. There will be no intra-patient dose escalation. Sorafenib will be administered orally at a dose of 400mg bid for 28 days in the all patients. Cisplatin at the dose of 10-20mg/m2 will be administered at day 1 and day8, and fluorouracil at the dose of 170-330mg/m2 will be administered continuously at day1-day5, and day8-day12 via the implanted catheter system. A cycle is defined as 28 days and 3 cycles of this combination therapy will be continued. At the end of each cycle, adverse effect will be evaluated and dose escalation will be determined. In Phase II, there will be 28 patients enrolled. Time to progression of this combination therapy at the recommended dose will be evaluated.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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. One treatment of hepatic arterial infusion chemotherapy without implanted catheter system is allowed.
  6. ECOG Performance status of 0 or 1.
  7. Cirrhotic status of Child-Pugh class A or B.
  8. 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 or PT 6 seconds above control
    • Total serum bilirubin 2 mg/dl
    • AST(SGOT) and ALT(SGPT) 5 × upper limit of normal
    • Serum creatinine 1.5 × upper limit of normal
    • Amylase 5 × upper limit of normal
  9. 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.
  5. Active chicken pox.
  6. Auditory disorder.
  7. Known history of HIV infection.
  8. Known metastatic or meningeal tumors.
  9. Extrahepatic tumor spread.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00933816

Locations
Japan
Kurume University Medical Center
Kurume, Fukuoka, Japan, 839-0863
Ogaki Municipal Hospital
Oogaki, Gifu, Japan, 503-8502
Kinki University School of Medicine
Osaka-Sayama, Osaka, Japan, 589-8511
Sponsors and Collaborators
Japan Liver Oncology Group
Investigators
Principal Investigator: Masatoshi Kudo Japan Liver Oncology Group
  More Information

No publications provided

Responsible Party: Japan Liver Oncology Group
ClinicalTrials.gov Identifier: NCT00933816     History of Changes
Other Study ID Numbers: JLOG0901
Study First Received: July 1, 2009
Last Updated: November 24, 2010
Health Authority: Japan: Institutional Review Board

Keywords provided by Japan Liver Oncology Group:
sorafenib
intraarterial infusion chemotherapy
Low dose FP
cisplatin
fluorouracil

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Adenocarcinoma
Carcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Cisplatin
Fluorouracil
Sorafenib
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014