A Phase II Study of Tegafur/Uracil (UFUR®)Plus Thalidomide for the Treatment of Advanced or Metastatic Hepatocellular Carcinoma (HCC)
Trial Snapshot
- Phase
- Phase 2
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- Primary Objective
Study Overview
Brief Summary
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:
- To determine the disease stabilization rate;
- To assess the progression-free survival and overall survival;
- To establish the safety profile;
- 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It was withdrawn from the European and Canadian markets in early 1960s because of its teratogenic effects .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 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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- 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.
- •Stage IV diseases by AJCC staging system, or loco-regional diseases which are not operable and not treatable by transarterial (chemo)embolization, percutaenous interventional therapy, or other empirical therapy of higher priority.
- •Measurable disease by RECIST criteria.
- •Karnofsky performance status ≧ 70%.
- •Age of 18 years or older.
- •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/mm
- •Serum creatinine ≦ 1.5 times the ULN.
- •Previous local therapy, such as radiotherapy, hepatic arterial embolization, radiofrequency ablation, percutaenous inverventional therapy, is allowed if the treatment was completed at least 6 weeks prior to the enrollment.
- •Sexually active patients, in conjunction with their partners, must practice birth control during and for 3 months after thalidomide therapy.
- •Written informed consent.
Exclusion Criteria
- •Concurrent radiotherapy, chemotherapy, immunotherapeutic drugs, corticosteroids or other investigational drug(s).
- •Previous exposure to the followings:
- •I.Cytotoxic chemotherapy; II.Thalidomide.
- •CNS metastasis.
- •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.
- •Organ transplantation.
- •Major systemic diseases those are inappropriate for systemic chemotherapy.
- •Mental status not fit for clinical trials.
- •Inability to take medications orally.
- •Pregnant or breast-feeding women.
- •Life expectancy less than 3 month.
- •Other malignancy with the exception of curatively treated non-melanoma skin cancer or cervical carcinoma in situ, from which the patient has been disease-free for 5 years.
Outcomes
Primary Outcomes
Primary Objective
To assess the overall response rate of tegafur/uracil (UFUR®) and thalidomide in the treatment of advanced or metastatic hepatocellular carcinoma.
Secondary Outcomes
- Secondary Objectives
- To determine the disease stabilization rate (CR+PR+SD).
- To assess the progression-free survival and overall survival.
- To establish the safety profile.
- To evaluate the changes of circulating factors indicating the angiogenesis activity and their correlation with objective tumor response.