Back to results

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

Primary Purpose

Advanced Hepatocellular Carcinoma

Status

Terminated

Phase

Phase 2

Locations

Egypt

Study Type

Interventional

Intervention

Sorafenib

sorafenib plus tegafur-uracil

About this trial

This is an interventional treatment trial for Advanced Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
- 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

Exclusion Criteria:

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)
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

Sites / Locations

Ain shams university
Cairo University Hospitals
National cancer institute
NHTMRI
National Liver Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Sorafenib alone.

sorafenib plus tegafur-uracil

Arm Description

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

Sorafenib 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

Outcomes

Primary Outcome Measures

time to progression (TTP):recist criteria

Secondary Outcome Measures

progression free survival (PFS):recist criteria

Time to symptomatic improvement:FHSI-8 questionnaire

Quality of Life Using EQ-5D questionnaire.

Full Information

NCT ID

NCT01539018

First Posted

February 21, 2012

Last Updated

August 3, 2015

Sponsor

Egyptian Society of Liver Cancer

1. Study Identification

Unique Protocol Identification Number

NCT01539018

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Terminated

Why Stopped

After interim results data showed no evidence of a difference between both groups

Study Start Date

January 2012 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Egyptian Society of Liver Cancer

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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 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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Advanced Hepatocellular Carcinoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

77 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sorafenib alone.

Arm Type

Active Comparator

Arm Description

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

Arm Title

sorafenib plus tegafur-uracil

Arm Type

Experimental

Arm Description

Sorafenib 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

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Other Intervention Name(s)

nexavar alone

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

sorafenib plus tegafur-uracil

Other Intervention Name(s)

nexavar plus UFT

Intervention Description

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

Primary Outcome Measure Information:

Title

time to progression (TTP):recist criteria

Time Frame

one year

Secondary Outcome Measure Information:

Title

progression free survival (PFS):recist criteria

Time Frame

one year

Title

Time to symptomatic improvement:FHSI-8 questionnaire

Time Frame

one year

Title

Quality of Life Using EQ-5D questionnaire.

Time Frame

one year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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 Exclusion Criteria: 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) 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

Overall Study Officials: