Hepatocellular CarcinomaPhase 2NCT00519688
UFUR Plus Thalidomide for Advanced Hepatocellular Carcinoma
A Phase 2 study testing Thalidomide and Tegafur/Uracil in people with Hepatocellular Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Thalidomide and Tegafur/Uracil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteTaiwan
- Study dates
- Jul 2006to Aug 2010
- 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 confirmed HCC or HBC/HCV carrier with hepatic tumor of α-FP>400 Stage IV dis. By AJCC KPS>70% Age>18 Liver function reserves:Child-Pugh Class A, ALT<5xUNL, Bil-T<1.5xUNL WBC>4000 or ANC>1500, PLT>75K, Cr<1.5xUNL Previous local therapy completed 6wks
Who cannot join
- Concurrent corticosteroids Previous exposure to C/T, Thalidomide CNS metastasis Concomitant illness: active infection, >NCIG2 neuropathy, Hx of seizures Organ transplantation
Trial locations and contacts
1 site in 1 country.
Taiwan1 site
Department of Oncology , National Taiwan University Hospital
Taipei
About this study
Official title: A Phase II Study of Tegafur/Uracil(UFUR) Plus Thalidomide for the Treatment of Advanced or Metastatic Hepatocellular Carcinoma (HCC)
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-tumor effect through the anti-angiogenesis activity (so-called"metronomic chemotherapy"). The efficacy of metronomic chemotherapy can be suppressed by VEGF/VEGFR signaling pathways and thus can bo further potentiated by agents blocking those survival signals of endothelial cell. In this regard, tegafur/uracil appears to be a good candidate for metronomic chemotherapy because tegafur/uracil and its metabolites bave already been shown to inhibit angiogenesis in several pre-clinical models.
Read the 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, tegafur/uracil 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. In several phase II studies conducted in Japan, tegafur/uracil induced a response rate of 0 to 17% in advanced HCC patients.
We hypothesize that combination of tegafur/uracil 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, tegafur/uracil appears to be a good candidate for metronomic chemotherapy because tegafur/uracil and its metabolites have already been shown to inhibit angiogenesis in several pre-clinical models.
The combination of tegafur/uracil 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
- Hepatocellular Carcinoma
- Being tested
- Thalidomide, Tegafur/Uracil
- Keywords
- tegafur, thalidomide, advanced hepatocellular carcinoma
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThalidomideDrug
Also called Thado
100 mg, BID
Tegafur/UracilDrug
Also called UFUR
125 mg/m2, based on tegafur, BID
| Study group | Role | What they receive |
|---|---|---|
| Thalidomide plus Tegafur/Uracil1 | Experimental | Thalidomide plus Tegafur/Uracil Receives: Drug: Thalidomide; Drug: Tegafur/Uracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the overall response rate of UFUR and thalidomide in the treatment of advanced HCC by RECIST criteria
Measured: Confirmed response within 4 weeks
Secondary outcomes (3)
To determine the disease stabilization rate.
Measured: 2 to 3 months
To assess the progression- free survival and overall survival.
Measured: 2 to 3 years
To establish the safety profile.
Toxicity criteria based on CTC-AE version 3
Measured: Additional 4 months after stopping the investigational drugs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2007 (estimated)
- Study startJul 2006
- Primary completionAug 2010
- Study completionAug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Chih-Hung Hsu, M.D. Ph.D., Study chair, Department of Oncology, National Taiwan University hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00519688
- Sponsor's protocol ID
- 940813
- Other IDs
- TTY-TU0510
- Status last verified
- Oct 2011
- First submitted
- 22 Aug 2007
- Last updated
- 17 Oct 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Oct 2011. 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
- NCT00519688
- Acronym / sponsor ID
- 940813
- Conditions
- Hepatocellular Carcinoma
- Keywords
- tegafur, thalidomide, advanced hepatocellular carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- Jul 2006
- Primary completion
- Aug 2010 (actual)
- Study completion
- Aug 2010 (actual)
- First posted
- 23 Aug 2007 (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.
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-tumor effect through the anti-angiogenesis activity (so-called"metronomic chemotherapy"). The efficacy of metronomic chemotherapy can be suppressed by VEGF/VEGFR signaling pathways and thus can bo further potentiated by agents blocking those survival signals of endothelial cell. In this regard, tegafur/uracil appears to be a good candidate for metronomic chemotherapy because tegafur/uracil 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, tegafur/uracil 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. In several phase II studies conducted in Japan, tegafur/uracil induced a response rate of 0 to 17% in advanced HCC patients.
We hypothesize that combination of tegafur/uracil 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, tegafur/uracil appears to be a good candidate for metronomic chemotherapy because tegafur/uracil and its metabolites have already been shown to inhibit angiogenesis in several pre-clinical models.
The combination of tegafur/uracil 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Thalidomide plus Tegafur/Uracil1 | Experimental | Drug: Thalidomide, Drug: Tegafur/UracilThalidomide plus Tegafur/Uracil |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Histologically confirmed HCC or HBC/HCV carrier with hepatic tumor of α-FP>400 Stage IV dis. By AJCC KPS>70% Age>18 Liver function reserves:Child-Pugh Class A, ALT<5xUNL, Bil-T<1.5xUNL WBC>4000 or ANC>1500, PLT>75K, Cr<1.5xUNL Previous local therapy completed 6wks
Key exclusion criteria (1 listed)
- Concurrent corticosteroids Previous exposure to C/T, Thalidomide CNS metastasis Concomitant illness: active infection, >NCIG2 neuropathy, Hx of seizures Organ transplantation
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 |
|---|---|---|
| ThalidomideAlso: Thado100 mg, BID | Drug | Thalidomide plus Tegafur/Uracil1 |
| Tegafur/UracilAlso: UFUR125 mg/m2, based on tegafur, BID | Drug | Thalidomide plus Tegafur/Uracil1 |
Primary outcome
To evaluate the overall response rate of UFUR and thalidomide in the treatment of advanced HCC by RECIST criteria
Time frame: Confirmed response within 4 weeks
3 secondary outcomes
To determine the disease stabilization rate.
Time frame: 2 to 3 months
To assess the progression- free survival and overall survival.
Time frame: 2 to 3 years
To establish the safety profile.
Time frame: Additional 4 months after stopping the investigational drugs
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Oct 2011.
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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.
Chih-Hung Hsu, M.D. Ph.D. study chair
Department of Oncology, National Taiwan University 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 and Tegafur/Uracil in people with Hepatocellular Carcinoma, run by National Taiwan University 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 1 inclusion and 1 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: finished, as of the sponsor's last update on 17 Oct 2011. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate the overall response rate of UFUR and thalidomide in the treatment of advanced HCC by RECIST criteria (time frame: Confirmed response within 4 weeks). 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 17 Oct 2011.