Carcinoma, HepatocellularPhase 2NCT00384800
A Phase II Study of Tegafur/Uracil (UFUR®)Plus Thalidomide for the Treatment of Advanced or Metastatic Hepatocellular Carcinoma (HCC)
A Phase 2 study testing Thalidomide(THADO), Tegafur/Uracil(UFUR) in people with Carcinoma, Hepatocellular, run by Far Eastern Memorial Hospital at 1 site in Taiwan.
Trial 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: 1. To determine the disease stabilization rate; 2. To assess the progression-free survival and overall survival; 3. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Hepatocellular
- What is being tested?
- Thalidomide(THADO), Tegafur/Uracil(UFUR)
- How many people
- 41 participants
- Where
- 1 siteTaiwan
- Study dates
- Sep 2006to not given
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Far Eastern Memorial Hospital
Taipei, Ban-Ciao, 220
Kun Huei Yeh, Ph.D., 886-2-89667000 ext. 1611, khyeh@mail.femh.org.tw
Kun Huei Yeh, Ph.D.
About this study
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.
Read the 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.
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.
- Conditions
- Carcinoma, Hepatocellular
- Being tested
- Thalidomide(THADO), Tegafur/Uracil(UFUR)
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Thalidomide(THADO), Tegafur/Uracil(UFUR)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
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 (5)
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2006 (estimated)
- Study startSep 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, HepatocellularStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Far Eastern Memorial Hospital
- Sponsor type
- University, hospital or other
- Investigators
- Kun Huei Yeh, Ph.D., Principal investigator, Far Eastern Memorial Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00384800
- Sponsor's protocol ID
- FEMH-94037
- Status last verified
- Mar 2006
- First submitted
- 4 Oct 2006
- Last updated
- 9 Feb 2009
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Tegafur/Uracil (UFUR®)Plus Thalidomide for the Treatment of Advanced or Metastatic Hepatocellular Carcinoma (HCC)
- ClinicalTrials.gov ID
- NCT00384800
- Acronym / sponsor ID
- FEMH-94037
- Conditions
- Carcinoma, Hepatocellular
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Far Eastern Memorial HospitalUniversity, hospital or other
- Study start
- Sep 2006
- First posted
- 6 Oct 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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%.
Key exclusion criteria (13 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Thalidomide(THADO), Tegafur/Uracil(UFUR) | Drug | – |
Primary outcome
Primary Objective
To assess the overall response rate of tegafur/uracil (UFUR®) and thalidomide in the treatment of advanced or metastatic hepatocellular carcinoma.
5 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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kun Huei Yeh, Ph.D. principal investigator
Far Eastern Memorial Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Thalidomide(THADO), Tegafur/Uracil(UFUR) in people with Carcinoma, Hepatocellular, run by Far Eastern Memorial Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Feb 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kun Huei Yeh, Ph.D. (886-2-89667000 ext. 1611, khyeh@mail.femh.org.tw), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary Objective. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Feb 2009.