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Sponsored by: |
Far Eastern Memorial Hospital |
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Information provided by: | Far Eastern Memorial Hospital |
ClinicalTrials.gov Identifier: | NCT00384800 |
Primary objective:
To evaluate the overall response rate of tegafur/uracil (UFUR®) and thalidomide in the treatment of advanced or metastatic hepatocellular carcinoma.
Secondary objectives:
Condition | Intervention | Phase |
---|---|---|
Carcinoma, Hepatocellular |
Drug: Thalidomide(THADO), Tegafur/Uracil(UFUR) |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study |
Estimated Enrollment: | 41 |
Study Start Date: | September 2006 |
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It was withdrawn from the European and Canadian markets in early 1960s because of its teratogenic effects .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 ratio:1:4). 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.
Tegafur/urail 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, which are traditionally indicated for the therapy of 5-FU-based chemotherapy, in Japan and Taiwan.
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-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, 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 tegafur/uracil (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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Histologically proven HCC, or HCC diagnosed by clinical criteria. The clinical diagnosis of HCC should is defined when all the following criteria are met:
I.Chronic hepatitis B or C virus carrier; II.Presence of hepatic tumor(s) with image findings (sonography, CT scan, etc) compatible with HCC and no evidence of other gastrointestinal tumors; III.A persistent elevation of serum α-fetoprotein (AFP) level of ≧ 400 ng/ml.
Adequate liver function reserves:
I.Class A according to Child-Pugh classification; II.Alanine aminotransferase (ALT) ≦ 5 times the ULN; III.Serum total bilirubin ≦ 1.5 times ULN.
Adequate bone marrow reserves:
White blood cell (WBC) ≧ 4,000/mm3 or absolute neutrophil count (ANC) ≧ 1,500/mm3;Platelets ≧ 75,000/mm3.
Exclusion Criteria:
Previous exposure to the followings:
I.Cytotoxic chemotherapy; II.Thalidomide.
Concomitant diseases that might be aggravated by investigational drugs:
I.Active or non-controlled infection; II.≧ NCI grade 2 peripheral neuropathy; III.History of seizures within the past 10 years or currently on anticonvulsant medication.
Contact: Kun Huei Yeh, Ph.D. | 886-2-89667000 ext 1611 | khyeh@mail.femh.org.tw |
Taiwan, Ban-Ciao | |
Far Eastern Memorial Hospital | Recruiting |
Taipei, Ban-Ciao, Taiwan, 220 | |
Contact: Kun Huei Yeh, Ph.D. 886-2-89667000 ext 1611 khyeh@mail.femh.org.tw | |
Principal Investigator: Kun Huei Yeh, Ph.D. |
Principal Investigator: | Kun Huei Yeh, Ph.D. | Far Eastern Memorial Hospital |
Study ID Numbers: | FEMH-94037 |
Study First Received: | October 4, 2006 |
Last Updated: | October 4, 2006 |
ClinicalTrials.gov Identifier: | NCT00384800 |
Health Authority: | Taiwan: Department of Health |
Liver Diseases Digestive System Neoplasms Thalidomide Carcinoma, Hepatocellular Tegafur Liver neoplasms Carcinoma |
Liver Neoplasms Digestive System Diseases Gastrointestinal Neoplasms Adenocarcinoma Neoplasms, Glandular and Epithelial Hepatocellular carcinoma |
Antimetabolites Anti-Infective Agents Neoplasms by Histologic Type Antimetabolites, Antineoplastic Molecular Mechanisms of Pharmacological Action Immunologic Factors Antineoplastic Agents Growth Substances Physiological Effects of Drugs Angiogenesis Inhibitors |
Immunosuppressive Agents Pharmacologic Actions Anti-Bacterial Agents Neoplasms Neoplasms by Site Therapeutic Uses Growth Inhibitors Angiogenesis Modulating Agents Leprostatic Agents |