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

NCT01131689 | Completed Phase 1

• 1 other identifier: 2008-10-009
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Hepatocellular Carcinoma

Keywords

metastatic HCC

Outcome Measures

Primary Outcomes (1)

• 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

Interventions

sorafenib, TS-1 DRUG

D1-14 S-1 dose of level 1/2/3/4 D1-21 Sorafenib 400mg twice daily Every 3 weeks-cycle

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically confirmed hepatocellular carcinoma (HCC) or a combination of radiologically compatible finding to HCC, alpha-fetoprotein\>400ng/mL and liver cirrhosis
• Inoperable disease as defined by
• 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
• Presence of extra-hepatic disease OR
• Main portal vein or hepatic vein involvement (invasion or tumor thrombus) OR
• The HCC must not be amenable to intra-arterial therapy or local ablative therapy
• Minimum life expectancy of 12 weeks
• Age\>18 years.
• ECOG Performance Status of 0-1
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
• Hemoglobin\>9.0 g/dl
• Absolute neutrophil count (ANC) \>1,500/mm3
• Platelet count \> 75,000/μl
• Total bilirubin \< 1.5 times the upper limit of normal
• ALT and AST \<5 x upper limit of normal

You may not qualify if:

• Decompensated cirrhosis or stage C according to the Child-Pugh Classification
• Other concomitant anticancer agent, including Tamoxifen and Interferon
• 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.
• History of HIV infection
• Active clinically serious infections (\> grade 2 CTCAE version 3.0)
• Symptomatic metastatic brain or meningeal tumors
• Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
• History of organ allograft
• Patients with evidence or history of bleeding diathesis
• Patients undergoing renal dialysis
• Radiotherapy during study or within 4 weeks of start of study drug.
• Major surgery within 4 weeks of start of study
• Autologous bone marrow transplant or stem cell rescue within 4 months of study
• Prior exposure to the study drug.
• 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).

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib; titanium silicide

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 25, 2010
• First Posted: May 27, 2010
• Study Start: September 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2011
• Last Updated: February 2, 2012

Record last verified: 2012-01

Locations

KR (1)