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AzTrials

Advanced Hepatocellular CarcinomaPhase 2NCT01539018

Sorafenib Plus Tegafur-uracil (UFT) Versus Sorafenib as First Line Systemic Treatment for Patients With Advanced Stage HCC, Unresectable & Not Eligible for Local Ablation and/or TACE

A Phase 2 study testing Sorafenib and sorafenib plus tegafur-uracil in people with Advanced Hepatocellular Carcinoma, run by Egyptian Society of Liver Cancer at 5 sites in Egypt.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

Unlike the Asian and western regions, The vast majority of the Egyptian/Arabic Hepatocellular Carcinoma (HCC) patients are hepatitis C virus (HCV) associated. According to the SHARP study subgroup analysis, it seems that HCV associated HCC patients derive the max benefit of Sorafenib, the absolute gain between the… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Hepatocellular Carcinoma
What is being tested?
Sorafenib and sorafenib plus tegafur-uracil
Could I receive a placebo?
No, everyone receives an active treatment
How many people
77 participants
Where
5 sitesEgypt
Study dates
Jan 2012to Jan 2015
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

  • 1-The patient must provide written informed consent prior to enrollment into the study.
  • 2-The patient must be at least 18 years of age. 3-Patients must have histologically or cytologically confirmed or radiologically confirmed (according to AASLD criteria) advanced (unresectable, and/or metastatic) HCC not eligible for local ablation or TACE.
  • 4-Patients must have measurable disease according to RECIST criteria (at least one uni-dimensional lesion measurable by CT-scan or MRI) 5-Patients must have a life expectancy of at least 12 weeks 6-Patients must have an Eastern Co-operative Oncology Group (ECOG) performance status of 0 -2, Child-Pugh class A and only B7 7-Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
  • Hemoglobin ≥ 9.0 g/dl
  • Absolute neutrophil count (ANC) ≥ 1,500/mm3
  • Platelet count ≥ 100,000/μl
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  • Total bilirubin ≤ 1.5 times the upper limit of normal
  • ALT and AST < 5 x upper limit of normal
  • Alkaline phosphatase ≤ 5 x upper limit of normal
  • PT-INR/PTT < 1.5 x upper limit of normal
  • Serum creatinine < 1.5 x upper limit
  • Amylase and lipase < 1.5 X the upper limit of normal 8-For patients, who have had major surgery or injury, the wound must be completely healed prior to receiving sorafenib treatment (4 weeks).
  • 9-Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation. Men use adequate birth control for at least 3 months after the last administration of sorafenib

Who cannot join

  • Excluded medical conditions:
  • History of cardiac disease: congestive heart failure > NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
  • History of HIV infection
  • Patients with Child-Pugh class C hepatic impairment
  • Patients with Child-Pugh class B (except 7 ) hepatic impairment
  • Active clinically serious infections (grade 2 NCI-CTC version 3.0)
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  • Symptomatic metastatic brain or meningeal tumors
  • Patients with seizure disorder requiring medication (such as steroids or antiepileptics)
  • History of organ allograft
  • Patients with evidence or history of bleeding due to OV
  • Patients undergoing renal dialysis
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma
  • Patients not fulfilling inclusion criteria.
  • Excluded therapies and medications, previous and concomitant:
  • Prior systemic anticancer chemotherapy or immunotherapy or targeted therapy is not allowed before study entry.
  • Hormonal therapy shouldn't be given within 2 weeks before study entry and is not allowed during the study.
  • Patients who failed previous transcatheter arterial chemoembolism must have at least 4 weeks treatment free interval before entering the study
  • Radiotherapy during study or within 3 weeks of start of study drug.
  • Major surgery within 4 weeks of start of study
  • Investigational drug therapy outside of this trial during or within 4 weeks of study entry
  • Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial.
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results
  • Known or suspected allergy to the investigational agent or any agent given in association with this trial
  • Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Egypt5 sites
  • Ain shams university

    Cairo

  • Cairo University Hospitals

    Cairo

  • National cancer institute

    Cairo

  • NHTMRI

    Cairo

  • National Liver Institute

    Monofeiya

Other trials in Egypt

About this study

Official title: A Phase II Trial of Sorafenib Plus Tegafur-uracil (UFT) vs. Sorafenib as First Line Systemic Treatment for Patients With Advanced Stage HCC, Unresectable & Not Eligible for Local Ablation &/or TACE

  • Unlike the Asian and western regions, The vast majority of the Egyptian/Arabic Hepatocellular Carcinoma (HCC) patients are hepatitis C virus (HCV) associated.
  • According to the SHARP study subgroup analysis, it seems that HCV associated HCC patients derive the max benefit of Sorafenib, the absolute gain between the Sorafenib arm \& the placebo in m OS = 7 months, HR=0.58 (95% CI: 0.37-0.91).
  • In spite of improvement in terms of overall survival (OS) and time to progression (TTP), in all studies where Sorafenib was compared to placebo, the Sorafenib arm was not accompanied by a significant volumetric reduction, and this may explains the lack of any symptomatic improvement (time to symptomatic progression (TTSP) almost identical)
  • Reviewing the chemotherapy outcome, although there is no convincing evidence in survival benefit to patients with advanced HCC, however true shrinkage (reduction in tumor size), has been consistently reported although the magnitude of response is lacking consistency.

This indicates the need for coupling Sorafenib to a chemotherapeutic agent but:

Read more
  • For patients with Hepatocellular Carcinoma, the toxicity profile of any chemotherapeutic agent of choice to be added to Sorafenib should be take in consideration
  • The agent to be added to Sorafenib should be effective in terms of Tumor Shrinkage \& with minimal toxicity regarding:
  • Cardio-toxicity
  • HFSR
  • Diarrhea
  • Hepato-toxicity
  • Bone marrow suppression (although not relevant to the toxicity profile of Sorafenib, yet the HCC patients may have HCV related thrombocytopenia and variable degree of hypersplenism related pancytopenia)

Circulatory Overload (Hypertension) Why Tegafur-uracil (UFT)?

  • Efficacy: For UFT, although the efficacy data in HCC are not as extensive as Doxorubicin, however in one phase II study UFT could improve survival when compared with conservative management.
  • UFT Toxicity Profile:

In a phase III trial to asses the compare Efficacy \& Safety of UFT with that of 5 FU in treatment of m CRC, Hematological toxicities were minimal (0% Grade ¾ leukopenia, neutropenia, febrile neutropenia, thrombocytopenia \& was 3% for anemia), while the most commonly seen SE was grade I \& II Diarrhea

•Accordingly UFT may be considered as a potential partner to Sorafenib in patients with advanced HCC.

Being tested
Sorafenib, sorafenib plus tegafur-uracil

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SorafenibDrug

    Also called nexavar alone

    Sorafenib 400 mg p.o. twice daily until progression or intolerable toxicity alone.

  • sorafenib plus tegafur-uracilDrug

    Also called nexavar plus UFT

    Sorafenib 400 mg p.o. twice daily until progression or intolerable toxicity and TEGAFUR-URACIL 125mg/m2 PO BID For 4 weeks and to be repeated on day 36 till progression or intolerance

Study groups in NCT01539018
Study groupRoleWhat they receive
Sorafenib alone.Active comparatorSorafenib 400 mg p.o. twice daily until progression or intolerable toxicity alone.
Receives: Drug: Sorafenib
sorafenib plus tegafur-uracilExperimentalSorafenib 400 mg p.o. twice daily continuously and UFT 125mg/m2 PO BID For 4 weeks and to be repeated on day 36 till progression or intolerance
Receives: Drug: sorafenib plus tegafur-uracil

What is being measured

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

  1. time to progression (TTP):recist criteria

    Measured: one year

Secondary outcomes (3)
  1. progression free survival (PFS):recist criteria

    Measured: one year

  2. Time to symptomatic improvement:FHSI-8 questionnaire

    Measured: one year

  3. Quality of Life Using EQ-5D questionnaire.

    Measured: one year

Timeline

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

  1. First posted27 Feb 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionJan 2015
  4. Study completionJan 2015

Why it stopped: After interim results data showed no evidence of a difference between both groups

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
77 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01539018
Sponsor's protocol ID
ESLC1 (SADAT study)
Status last verified
Aug 2015
First submitted
21 Feb 2012
Last updated
5 Aug 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Sorafenib and sorafenib plus tegafur-uracil in people with Advanced Hepatocellular Carcinoma, run by Egyptian Society of Liver Cancer at 5 sites in Egypt.

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 13 inclusion and 24 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: stopped early, as of the sponsor's last update on 5 Aug 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Egypt. 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 was stopped early (reason given: After interim results data showed no evidence of a difference between both groups). Results are not available in the source record.

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?

time to progression (TTP):recist criteria (time frame: one year). 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 5 Aug 2015.

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