Ignite Creation Date:
2024-05-05 @ 5:07 PM
Last Modification Date:
2024-10-26 @ 9:28 AM
Study NCT ID:
NCT00384800
Status:
UNKNOWN
Last Update Posted:
2009-02-09
First Post:
2006-10-04
Brief Title:
A Phase II Study of TegafurUracil UFURPlus Thalidomide for the Treatment of Advanced or Metastatic Hepatocellular Carcinoma HCC
Sponsor:
Far Eastern Memorial Hospital
Organization:
Far Eastern Memorial Hospital
Study Overview
Official Title:
None
Status:
UNKNOWN
Status Verified Date:
2006-03
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Primary objective
To evaluate the overall response rate of tegafururacil UFUR and thalidomide in the treatment of advanced or metastatic hepatocellular carcinoma
Secondary objectives
1 To determine the disease stabilization rate
2 To assess the progression-free survival and overall survival
3 To establish the safety profile
4 To evaluate the changes of circulating factors indicating the angiogenesis activity and their correlation with objective tumor response
To evaluate the overall response rate of tegafururacil UFUR and thalidomide in the treatment of advanced or metastatic hepatocellular carcinoma
Secondary objectives
1 To determine the disease stabilization rate
2 To assess the progression-free survival and overall survival
3 To establish the safety profile
4 To evaluate the changes of circulating factors indicating the angiogenesis activity and their correlation with objective tumor response
Detailed Description:
Thalidomide is 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It was withdrawn from the European and Canadian markets in early 1960s because of its teratogenic effects It was not until 1998 when FDA approved thalidomide in the US for the treatment of erythema nodosum leprosum ENL
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 such as myeloma hormone-refractory prostate cancer high-grade glioma renal cell carcinoma and melanoma
UFUR is a composite drug composed of 100mg tegafur and 224mg uracil molar ratio14 It was marketed as UFT in Japan and marketed as UFUR in Taiwan
Tegafur a prodrug of 5-FU is easily absorbed though the gastro-intestinal tract slowly metabolized to 5-FU mainly in liver Uracil is an inhibitor of dihydro-pyrimidine dehydrogenase DPD the rate-limiting enzyme of 5-FU degradation
Tegafururail is expected to maintain a stably high concentration in liver and in circulation Tegafururacil has been approved for the indications of advanced gastric cancer and colorectal cancer which are traditionally indicated for the therapy of 5-FU-based chemotherapy in Japan and Taiwan
We hypothesize that combination of tegafururacil 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-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 VEGFVEGFR signaling pathways and thus can be further potentiated by agents blocking those survival signals of endothelial cells In this regard UFUR appears to be a good candidate for metronomic chemotherapy because UFUR and its metabolites have already been shown to inhibit angiogenesis in several pre-clinical models
The combination of tegafururacil UFUR 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
It was withdrawn from the European and Canadian markets in early 1960s because of its teratogenic effects It was not until 1998 when FDA approved thalidomide in the US for the treatment of erythema nodosum leprosum ENL
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 such as myeloma hormone-refractory prostate cancer high-grade glioma renal cell carcinoma and melanoma
UFUR is a composite drug composed of 100mg tegafur and 224mg uracil molar ratio14 It was marketed as UFT in Japan and marketed as UFUR in Taiwan
Tegafur a prodrug of 5-FU is easily absorbed though the gastro-intestinal tract slowly metabolized to 5-FU mainly in liver Uracil is an inhibitor of dihydro-pyrimidine dehydrogenase DPD the rate-limiting enzyme of 5-FU degradation
Tegafururail is expected to maintain a stably high concentration in liver and in circulation Tegafururacil has been approved for the indications of advanced gastric cancer and colorectal cancer which are traditionally indicated for the therapy of 5-FU-based chemotherapy in Japan and Taiwan
We hypothesize that combination of tegafururacil 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-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 VEGFVEGFR signaling pathways and thus can be further potentiated by agents blocking those survival signals of endothelial cells In this regard UFUR appears to be a good candidate for metronomic chemotherapy because UFUR and its metabolites have already been shown to inhibit angiogenesis in several pre-clinical models
The combination of tegafururacil UFUR 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None