DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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

Information source: Egyptian Society of Liver Cancer
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Advanced Hepatocellular Carcinoma

Intervention: Sorafenib (Drug); sorafenib plus tegafur-uracil (Drug)

Phase: Phase 2

Status: Terminated

Sponsored by: Egyptian Society of Liver Cancer

Official(s) and/or principal investigator(s):
Hamdy Abdelazim, MD/PhD, Study Chair, Affiliation: Cairo University
Hesham Atef, MD/PhD, Principal Investigator, Affiliation: Cairo University
Ashraf Abdelaziz, MD/PhD, Principal Investigator, Affiliation: Cairo University
Mohammed Shaker, MD/PhD, Principal Investigator, Affiliation: Ain Shams University
Imam Waked, MD/PhD, Principal Investigator, Affiliation: Monofeiya university
Heba Elzawahry, MD/PhD, Principal Investigator, Affiliation: Cairo university, national cancer institute
Mohammed Ezz alarab, MD/PhD, Principal Investigator, Affiliation: NTMRI
Omar Abdel-Rahman, M.D./M.Sc., Study Director, Affiliation: Ain Shams University

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.

Clinical Details

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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: time to progression (TTP):recist criteria

Secondary outcome:

progression free survival (PFS):recist criteria

Time to symptomatic improvement:FHSI-8 questionnaire

Quality of Life Using EQ-5D questionnaire.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Ain shams university, Cairo, Egypt

Cairo University Hospitals, Cairo, Egypt

National cancer institute, Cairo, Egypt

NHTMRI, Cairo, Egypt

National Liver Institute, Monofeiya, Egypt

Additional Information

Starting date: January 2012
Last updated: August 3, 2015

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017