Ignite Creation Date:
2024-05-05 @ 6:38 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00519688
Status:
COMPLETED
Last Update Posted:
2011-10-17
First Post:
2007-08-22
Brief Title:
UFUR Plus Thalidomide for Advanced Hepatocellular Carcinoma
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
A Phase II Study of TegafurUracilUFUR Plus Thalidomide for the Treatment of Advanced or Metastatic Hepatocellular Carcinoma HCC
Status:
COMPLETED
Status Verified Date:
2011-10
Last Known Status:
None
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:
We hypothesize that combination of tegafururacilUFUR and thalidomide both of which have been shown to be active in some HCC patientsmay 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-calledmetronomic chemotherapy The efficacy of metronomic chemotherapy can be suppressed by VEGFVEGFR signaling pathways and thus can bo further potentiated by agents blocking those survival signals of endothelial cell In this regard tegafururacil appears to be a good candidate for metronomic chemotherapy because tegafururacil 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derivative first developed in 1950s was marketed as a sedative tranquilizer and antiemetic for morning sickness It was withdrawn from the European and Canadian markets in early 1960s because of its teratogenic effects In recent years thalidomide is emerging as a novel treatment for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 tegafururacil 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 In several phase II studies conducted in Japan tegafururacil induced a response rate of 0 to 17 in advanced HCC patients
We hypothesize that combination of tegafururacil 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 tegafururacil appears to be a good candidate for metronomic chemotherapy because tegafururacil and its metabolites have already been shown to inhibit angiogenesis in several pre-clinical models
The combination of tegafururacil 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
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 tegafururacil 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 In several phase II studies conducted in Japan tegafururacil induced a response rate of 0 to 17 in advanced HCC patients
We hypothesize that combination of tegafururacil 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 tegafururacil appears to be a good candidate for metronomic chemotherapy because tegafururacil and its metabolites have already been shown to inhibit angiogenesis in several pre-clinical models
The combination of tegafururacil 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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| TTY-TU0510 | None | None | None |