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

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01131689
• Other study ID #: 2008-10-009
• Status: Completed
• Phase: Phase 1
• First received: May 25, 2010
• Last updated: January 31, 2012
• Start date: September 2009
• Est. completion date: September 2011

Study information

• Verified date: January 2012
• Source: Samsung Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: September 2011
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Samsung Medical Center

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MTD	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)	1 year	Yes