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

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma Drug: sorafenib, TS-1 Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Trial of S-1 in Combination With Sorafenib for Patients With Advanced Hepatocellular Carcinoma
Study Start Date : September 2009
Actual Primary Completion Date : September 2010
Actual Study Completion Date : September 2011

Resource links provided by the National Library of Medicine

Intervention Details:
  • 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

Primary Outcome Measures :
  1. 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)

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01131689

Korea, Republic of
Samsung Medical Center
Seoul, Korea, Republic of
Sponsors and Collaborators
Samsung Medical Center

Responsible Party: Samsung Medical Center Identifier: NCT01131689     History of Changes
Other Study ID Numbers: 2008-10-009
First Posted: May 27, 2010    Key Record Dates
Last Update Posted: February 2, 2012
Last Verified: January 2012

Keywords provided by Samsung Medical Center:
metastatic HCC

Additional relevant MeSH terms:
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs