UFUR Plus Thalidomide for Advanced Hepatocellular Carcinoma
Primary Purpose
Hepatocellular Carcinoma
Status
Completed
Phase
Phase 2
Locations
Taiwan
Study Type
Interventional
Intervention
Thalidomide
Tegafur/Uracil
Sponsored by

About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring tegafur, thalidomide, advanced hepatocellular carcinoma
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed HCC or HBC/HCV carrier with hepatic tumor of α-FP>400 Stage IV dis. By AJCC KPS>70% Age>18 Liver function reserves:Child-Pugh Class A, ALT<5xUNL, Bil-T<1.5xUNL WBC>4000 or ANC>1500, PLT>75K, Cr<1.5xUNL Previous local therapy completed 6wks
Exclusion Criteria:
- Concurrent corticosteroids Previous exposure to C/T, Thalidomide CNS metastasis Concomitant illness: active infection, >NCIG2 neuropathy, Hx of seizures Organ transplantation
Sites / Locations
- Department of Oncology , National Taiwan University Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Thalidomide plus Tegafur/Uracil1
Arm Description
Thalidomide plus Tegafur/Uracil
Outcomes
Primary Outcome Measures
To evaluate the overall response rate of UFUR and thalidomide in the treatment of advanced HCC by RECIST criteria
Secondary Outcome Measures
To determine the disease stabilization rate.
To assess the progression- free survival and overall survival.
To establish the safety profile.
Toxicity criteria based on CTC-AE version 3
Full Information
NCT ID
NCT00519688
First Posted
August 22, 2007
Last Updated
October 13, 2011
Sponsor
National Taiwan University Hospital
1. Study Identification
Unique Protocol Identification Number
NCT00519688
Brief Title
UFUR Plus Thalidomide for Advanced Hepatocellular Carcinoma
Official Title
A Phase II Study of Tegafur/Uracil(UFUR) Plus Thalidomide for the Treatment of Advanced or Metastatic Hepatocellular Carcinoma (HCC)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2011
Overall Recruitment Status
Completed
Study Start Date
July 2006 (undefined)
Primary Completion Date
August 2010 (Actual)
Study Completion Date
August 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
We hypothesize that combination of tegafur/uracil(UFUR) and thalidomide, both of which have been shown to be active in some HCC patients,may be a highly useful regimen for the treatment of advanced HCC. There are several rationales underlying this combination. First, anti-angiogenesis therapy may improve the efficacy of chemotherapy by normalizing the abnormal vasculature in tumors, and thus improving the delivery of chemotherapeutic agents to the tumor cells. Second, chemotherapeutic drugs given in a low-dose, un interrupted, and protracted way can induce anti-tumor effect through the anti-angiogenesis activity (so-called"metronomic chemotherapy"). The efficacy of metronomic chemotherapy can be suppressed by VEGF/VEGFR signaling pathways and thus can bo further potentiated by agents blocking those survival signals of endothelial cell. In this regard, tegafur/uracil appears to be a good candidate for metronomic chemotherapy because tegafur/uracil and its metabolites bave already been shown to inhibit angiogenesis in several pre-clinical models.
Detailed Description
Thalidomide, a glutamic acid derivative first developed in 1950s, was marketed as a sedative, tranquilizer, and antiemetic for morning sickness. It was withdrawn from the European and Canadian markets in early 1960s because of its teratogenic effects. In recent years, thalidomide is emerging as a novel treatment for cancer because of its anti-angiogenic properties. The clinical efficacy has been demonstrated in various types of human cancers, including HCC.
Tegafur and uracil is a composite drug, which has been marketed as UFT® in Japan and marketed as UFUR® in Taiwan. Tegafur, a prodrug of 5-FU, is easily absorbed though the gastrointestinal tract slowly metabolized to 5-FU mainly in liver. Uracil is an inhibitor of dihydropyrimidine dehydrogenase (DPD), the rate-limiting enzyme of 5-FU degradation. Therefore, tegafur/uracil is expected to maintain a stably high concentration in liver and in circulation. Tegafur/uracil has been approved for the indications of advanced gastric cancer and colorectal cancer. In several phase II studies conducted in Japan, tegafur/uracil induced a response rate of 0 to 17% in advanced HCC patients.
We hypothesize that combination of tegafur/uracil and thalidomide, both of which have been shown to be active in some HCC patients, may be a highly useful regimen for the treatment of advanced HCC. There are several rationales underlying this combination. First, anti-angiogenesis therapy may improve the efficacy of chemotherapy by normalizing the abnormal vasculature in tumors, and thus improving the delivery of chemotherapeutic agents to the tumor cells. Second, chemotherapeutic drugs given in a low-dose, un-interrupted, and protracted way can induce anti-neoplasm effect through the anti-angiogenesis activity. What so-called "metronomic chemotherapy" is based on direct targeting of the activation, growth, and proliferation of vascular endothelial cells by cytotoxic chemotherapeutic agents. The anti-angiogenesis effect of metronomic chemotherapy is suppressed by VEGF/VEGFR signaling pathways and thus can be further potentiated by agents blocking those survival signals of endothelial cells. In this regard, tegafur/uracil appears to be a good candidate for metronomic chemotherapy because tegafur/uracil and its metabolites have already been shown to inhibit angiogenesis in several pre-clinical models.
The combination of tegafur/uracil and thalidomide has clinical advantages for patients with HCC. Both drugs are orally active, thus are convenient to be given on an out-patient basis. More importantly, the low and non-overlapping toxicity profiles of the two drugs make the combination relatively safe in patients of HCC.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
tegafur, thalidomide, advanced hepatocellular carcinoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
44 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Thalidomide plus Tegafur/Uracil1
Arm Type
Experimental
Arm Description
Thalidomide plus Tegafur/Uracil
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Other Intervention Name(s)
Thado
Intervention Description
100 mg, BID
Intervention Type
Drug
Intervention Name(s)
Tegafur/Uracil
Other Intervention Name(s)
UFUR
Intervention Description
125 mg/m2, based on tegafur, BID
Primary Outcome Measure Information:
Title
To evaluate the overall response rate of UFUR and thalidomide in the treatment of advanced HCC by RECIST criteria
Time Frame
Confirmed response within 4 weeks
Secondary Outcome Measure Information:
Title
To determine the disease stabilization rate.
Time Frame
2 to 3 months
Title
To assess the progression- free survival and overall survival.
Time Frame
2 to 3 years
Title
To establish the safety profile.
Description
Toxicity criteria based on CTC-AE version 3
Time Frame
Additional 4 months after stopping the investigational drugs
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed HCC or HBC/HCV carrier with hepatic tumor of α-FP>400 Stage IV dis. By AJCC KPS>70% Age>18 Liver function reserves:Child-Pugh Class A, ALT<5xUNL, Bil-T<1.5xUNL WBC>4000 or ANC>1500, PLT>75K, Cr<1.5xUNL Previous local therapy completed 6wks
Exclusion Criteria:
Concurrent corticosteroids Previous exposure to C/T, Thalidomide CNS metastasis Concomitant illness: active infection, >NCIG2 neuropathy, Hx of seizures Organ transplantation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chih-Hung Hsu, M.D. Ph.D.
Organizational Affiliation
Department of Oncology, National Taiwan University hospital
Official's Role
Study Chair
Facility Information:
Facility Name
Department of Oncology , National Taiwan University Hospital
City
Taipei
Country
Taiwan
12. IPD Sharing Statement
Learn more about this trial
UFUR Plus Thalidomide for Advanced Hepatocellular Carcinoma
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