Trial of S-1 in Combination With Sorafenib for Patients With Advanced Hepatocellular Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01131689
Recruitment Status : Completed
First Posted : May 27, 2010
Last Update Posted : February 2, 2012
Information provided by (Responsible Party):
Samsung Medical Center

May 25, 2010
May 27, 2010
February 2, 2012
September 2009
September 2010   (Final data collection date for primary outcome measure)
MTD [ Time Frame: 1 year ]

Primary objectives:

1. To determine maximal tolerated dose (MTD) of S-1 combined with fixed dose of sorafenib 400mg twice daily.

Secondary objectives:

1. To evaluate toxicity profiles and dose-limiting toxicity (DLT)

Same as current
Complete list of historical versions of study NCT01131689 on Archive Site
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Trial of S-1 in Combination With Sorafenib for Patients With Advanced Hepatocellular Carcinoma
Phase 1 Trial of S-1 in Combination With Sorafenib for Patients With Advanced Hepatocellular Carcinoma
In preclinical studies, 5-fluorouracil, one of the active metabolites of S-1, showed synergistic effect to sorafenib in human colon carcinoma cell lines. Therefore, sorafenib combined with S-1 might be more effective treatment for patients with advanced HCC than sorafenib monotherapy. The investigators propose to conduct a phase I study to determine maximal tolerated dose (MTD) of S-1 in combination with fixed dose of sorafenib in patients with advanced HCC
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Phase 1
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hepatocellular Carcinoma
Drug: sorafenib, TS-1
D1-14 S-1 dose of level 1/2/3/4 D1-21 Sorafenib 400mg twice daily Every 3 weeks-cycle
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
September 2011
September 2010   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Patients with histologically confirmed hepatocellular carcinoma (HCC) or a combination of radiologically compatible finding to HCC, alpha-fetoprotein>400ng/mL and liver cirrhosis
  2. Inoperable disease as defined by

    1. Localized disease in a portion of the liver that doses not allow the possibility of complete surgical removal of the tumor with a clear resection margin OR
    2. Presence of extra-hepatic disease OR
    3. Main portal vein or hepatic vein involvement (invasion or tumor thrombus) OR
    4. The HCC must not be amenable to intra-arterial therapy or local ablative therapy
  3. Minimum life expectancy of 12 weeks
  4. Age>18 years.
  5. ECOG Performance Status of 0-1
  6. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

    1. Hemoglobin>9.0 g/dl
    2. Absolute neutrophil count (ANC) >1,500/mm3
    3. Platelet count > 75,000/μl
    4. Total bilirubin < 1.5 times the upper limit of normal
    5. ALT and AST <5 x upper limit of normal
    6. Albumin >= 3g/dL
    7. PT-INR/PTT <1.5 x upper limit of normal
    8. Serum creatinine < 1.5 x upper limit of normal or Creatinine clearance >=50mL/min
  7. Signed and dated informed consent before the start of specific protocol procedures.

Exclusion Criteria:

  1. Decompensated cirrhosis or stage C according to the Child-Pugh Classification
  2. Chemo-embolization within 8 weeks of inclusion
  3. Other concomitant anticancer agent, including Tamoxifen and Interferon
  4. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension.
  5. History of HIV infection
  6. Active clinically serious infections (> grade 2 CTCAE version 3.0)
  7. Symptomatic metastatic brain or meningeal tumors
  8. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
  9. History of organ allograft
  10. Patients with evidence or history of bleeding diathesis
  11. Patients undergoing renal dialysis
  12. Radiotherapy during study or within 4 weeks of start of study drug.
  13. Major surgery within 4 weeks of start of study
  14. Autologous bone marrow transplant or stem cell rescue within 4 months of study
  15. Prior exposure to the study drug.
  16. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial (and men for at least 3 months after last administration of study medication).
  17. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  18. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study
  19. Patients unable to swallow oral medications.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
Korea, Republic of
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Samsung Medical Center
Samsung Medical Center
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Samsung Medical Center
January 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP