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Hepatocellular CarcinomaPhase 2NCT00464919

Sorafenib Plus Tegafur/Uracil (UFUR®) for Hepatocellular Carcinoma (HCC)

A Phase 2 study testing Sorafenib and tegafur/uracil (UFUR®) in people with Hepatocellular Carcinoma, run by National Taiwan University Hospital at 1 site in Taiwan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The prognosis for patients with metastatic or locally advanced hepatocellular carcinoma (HCC) is poor. The role of conventional systemic chemotherapy has been very limited because most chemotherapeutic agents are in-effective and relative toxic to HCC patients who tend to have poor organ function reserves due to liver… 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?
Sorafenib and tegafur/uracil (UFUR®)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteTaiwan
Study dates
Apr 2007to Mar 2009
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

  • Age > 18 years;
  • ECOG PS 0-2;
  • Histologically or cytologically documented unresectable and/or metastatic HCC;
  • Measurable disease by RECIST criteria;
  • Previous local therapy completed > 6 weeks;
  • Any acute toxicity (CTC-AE) < grade 1;
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  • Child-Pugh A;
  • Liver transaminases ≤ 5 x ULN;
  • Albumin ≥ 2.8 g/dl;
  • Serum total bilirubin ≤ 3 mg/dl;
  • INR ≤ 2.3 or PT ≤ 6 seconds above control;
  • WBC ≥ 3,000/µl;
  • ANC ≥ 1,500/µl;
  • Platelets ≥ 100,000/µl;
  • Hb ≥ 8.5 g/dl;
  • Creatinine ≤ 1.5 x ULN; AND
  • Amylase and lipase < 1.5 x ULN

Who cannot join

  • Metastatic brain/leptomeningeal tumors;
  • Prior or concomitant systemic anti-cancer treatment for HCC, including:
  • Systemic chemotherapy (TACE is allowed)
  • Immunotherapy
  • Hormonal therapy (hormonal therapy used for supportive used is allowed)
  • Raf-kinase inhibitors
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  • MEK inhibitors
  • Farnesyl transferase inhibitors
  • VEGF/VEGFR- inhibitors or other anti-angiogenesis agents
  • Investigational anti-cancer agents
  • Severe and/or uncontrolled medical conditions:
  • Uncontrolled high blood pressure
  • History of poor compliance with anti-hypertensive agents
  • Active or uncontrolled infection
  • Unstable angina
  • CHF
  • MI or CVA < 6 months
  • GI bleeding < 30 days
  • Unable to take oral medications
  • Severe renal impairment which requires dialysis; proteinuria > grade 2;
  • BMT or stem cell rescue < 4 months; organ transplant;
  • HIV infection;
  • Major surgical procedure, open biopsy, or significant traumatic injury < 4 weeks or those who receive minor surgical procedures (e.g. core biopsy or fine needle aspiration) within 2 weeks;
  • Receive central venous line placement within 7 days;
  • Patients who anticipate receiving major surgery during the course of the study;
  • Use rifampin, St. John's Wort [Hypericum perforatum];
  • Patients taking narrow therapeutic index medications will be monitored closely. These include warfarin, phenytoin, quinidine, carbamazepine, phenobarbital, cyclosporine, and digoxin; OR
  • Patients for whom tegafur is contra-indicated

Trial locations and contacts

1 site in 1 country.

Taiwan1 site

  • National Taiwan University Hospital

    Taipei, 100

Other trials in Taiwan

About this study

Official title: A Phase II Study of Sorafenib Plus Tegafur/Uracil for the Treatment of Advanced or Metastatic Hepatocellular Carcinoma

The prognosis for patients with metastatic or locally advanced hepatocellular carcinoma (HCC) is poor. The role of conventional systemic chemotherapy has been very limited because most chemotherapeutic agents are in-effective and relative toxic to HCC patients who tend to have poor organ function reserves due to liver cirrhosis. The molecular-targeted therapy, which aims at deranged signaling pathways of cancer cells or their microenvironment, holds promise for HCC.

Sorafenib (BAY 43-9006), a novel bi-aryl urea, is a potent inhibitor of VEGFR2 and Raf kinase. The clinical activity of sorafenib in HCC has been tested in a phase II study (Bayer study 10874), which enrolled a total of 137 advanced HCC patients. There were 4% of documented partial response, 5% of minor response, and 55% of stable disease. The 6- month progression -free for the cohort was 40%. Currently, there are two on-going large-scale randomized trials of sorafenib in advanced HCC patients worldwide.

Read the detailed description

The prognosis for patients with metastatic or locally advanced hepatocellular carcinoma (HCC) is poor. The role of conventional systemic chemotherapy has been very limited because most chemotherapeutic agents are in-effective and relative toxic to HCC patients who tend to have poor organ function reserves due to liver cirrhosis. The molecular-targeted therapy, which aims at deranged signaling pathways of cancer cells or their microenvironment, holds promise for HCC.

Sorafenib (BAY 43-9006), a novel bi-aryl urea, is a potent inhibitor of VEGFR2 and Raf kinase. The clinical activity of sorafenib in HCC has been tested in a phase II study (Bayer study 10874), which enrolled a total of 137 advanced HCC patients. There were 4% of documented partial response, 5% of minor response, and 55% of stable disease. The 6- month progression -free for the cohort was 40%. Currently, there are two on-going large-scale randomized trials of sorafenib in advanced HCC patients worldwide.In this study proposal, we propose to combine sorafenib with metronomic chemotherapy in the treatment of advanced HCC patients. It has been recently demonstrated that cytotoxic chemotherapy, when given in a low-dose, continuous, and uninterrupted way (i.e. the "metronomic" chemotherapy), inhibits tumor angiogenesis. The anti-angiogenesis effect of metronomic chemotherapy can be potentiated by combining the inhibitors of VEGF/VEGFR pathway. UFUR®, a composite drug composed of tegafur and uracil, is an orally active 5-fluorouracil (5-FU) preparation. The activity of tegafur/uracil in HCC has been tested in two relatively small-scale phase II studies, with objective tumor response rates ranging from 0~18%. Interestingly, tegafur and its metabolites, including γ-hydroxybutyric acid and γ-butyrolactone, have been shown to be potent inhibitors of angiogenesis in several preclinical models. Therefore, tegafur/uracil (UFUR®), which has potential anti-HCC activity and interesting anti-angiogenesis activity, is an ideal candidate drug to improve the efficacy of sorafenib in HCC.

Being tested
Sorafenib, tegafur/uracil (UFUR®)
Keywords
Advance, 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.

Study groups in NCT00464919
Study groupRoleWhat they receive
AExperimentalNot described
Receives: Drug: Sorafenib; Drug: tegafur/uracil (UFUR®)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To determine the progression- free survival of sorafenib plus tegafur/uracil (UFUR®) for the treatment of advanced or metastatic HCC.

    Measured: 2007~2008

Secondary outcomes (6)

  1. The 6-month progression-free survival rate.

    Measured: 2007~2008

  2. The objective tumor response rate.

    Measured: 2007~2008

  3. The disease stabilization rate (complete response + partial response + stable disease for at least 2 months).

    Measured: 2007~2008

  4. The overall survival.

    Measured: 2007~2008

  5. The safety profile.

    Measured: 2007~2008

  6. To evaluate the changes of circulating biomarkers indicating the angiogenesis activity and their correlation with objective tumor response.

    Measured: 2007~2008

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2007 (estimated)
  2. Study startApr 2007
  3. Study completionMar 2009

Resources

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
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00464919
Sponsor's protocol ID
950914
Status last verified
Jun 2009
First submitted
23 Apr 2007
Last updated
7 Jul 2009
Results posted
No
Data monitoring committee
Yes

Publications

  • Hsu CY, Shen YC, Yu CW, Hsu C, Hu FC, Hsu CH, Chen BB, Wei SY, Cheng AL, Shih TT. Dynamic contrast-enhanced magnetic resonance imaging biomarkers predict survival and response in hepatocellular carcinoma patients treated with sorafenib and metronomic tegafur/uracil. J Hepatol. 2011 Oct;55(4):858-65. doi: 10.1016/j.jhep.2011.01.032. Epub 2011 Feb 19.

    PubMed 21338641

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sorafenib and tegafur/uracil (UFUR®) 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 17 inclusion and 28 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 7 Jul 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?

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 determine the progression- free survival of sorafenib plus tegafur/uracil (UFUR®) for the treatment of advanced or metastatic HCC. (time frame: 2007~2008). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00464919, which also lists 1 linked publication.

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 7 Jul 2009.

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