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

NCT01539018 | Terminated Phase 2 DMC

• 1 other identifier: ESLC1 (SADAT study)
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 5

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.

Conditions

Advanced Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• time to progression (TTP):recist criteria

  one year

Secondary Outcomes (3)

• progression free survival (PFS):recist criteria

  one year

• Time to symptomatic improvement:FHSI-8 questionnaire

  one year

• Quality of Life Using EQ-5D questionnaire.

  one year

Study Arms (2)

Sorafenib alone.

ACTIVE COMPARATOR

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

Drug: Sorafenib

sorafenib plus tegafur-uracil

EXPERIMENTAL

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

Drug: sorafenib plus tegafur-uracil

Interventions

Sorafenib DRUG

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

Also known as: nexavar alone

Sorafenib alone.

sorafenib plus tegafur-uracil DRUG

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

Also known as: nexavar plus UFT

sorafenib plus tegafur-uracil

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient must provide written informed consent prior to enrollment into the study.
• 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.
• 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).
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Egyptian Society of Liver Cancer: lead

Study Sites (5)

Ain shams university

Cairo, Egypt

Location

Cairo University Hospitals

Cairo, Egypt

Location

National cancer institute

Cairo, Egypt

Location

NHTMRI

Cairo, Egypt

Location

National Liver Institute

Monofeiya, Egypt

Location

MeSH Terms

Interventions

Sorafenib; Tegafur

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Fluorouracil; Uracil; Pyrimidinones; Pyrimidines

Study Officials

• Hamdy Abdelazim, MD/PhD

  Cairo University

  STUDY CHAIR

• Hesham Atef, MD/PhD

  Cairo University

  PRINCIPAL INVESTIGATOR

• Ashraf Abdelaziz, MD/PhD

  Cairo University

  PRINCIPAL INVESTIGATOR

• Mohammed Shaker, MD/PhD

  Ain Shams University

  PRINCIPAL INVESTIGATOR

• Imam Waked, MD/PhD

  Monofeiya university

  PRINCIPAL INVESTIGATOR

• Heba Elzawahry, MD/PhD

  Cairo university, national cancer institute

  PRINCIPAL INVESTIGATOR

• Mohammed Ezz alarab, MD/PhD

  NTMRI

  PRINCIPAL INVESTIGATOR

• Omar Abdel-Rahman, M.D./M.Sc.

  Ain Shams University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 21, 2012
• First Posted: February 27, 2012
• Study Start: January 1, 2012
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: August 5, 2015

Record last verified: 2015-08

Locations

EG (5)