Sorafenib In Egyptian Patients With Hepatocellular Carcinoma.

Pharmacogenetic Study of Sorafenib In Egyptian Patients With Hepatocellular Carcinoma.

This study aims to determine the predictive effect of ATG10 and IL6 genetic polymorphisms in safety and efficacy of sorafenib used for the treatment of Egyptian HCC patients. Moreover, this study will determine the association between genetic polymorphisms of ATG10 and IL6 with HCC severity.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Sorafenib Tablets

Detailed Description

A prospective pharmcogentic study for Egyptian HCC patients treating with oral sorafenib.

1. Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy, Damanhour University.
2. 100 patients diagnosed with HCC for whom Sorafenib therapy is prescribed (400 mg twice daily) or (200mg twice daily),. will be recruited from Mansoura University Hospital, Mansoura, Egypt.
3. At baseline and follow up visits after Sorafenib, all patients will be assessed for complete blood count (CBC), kidney function, liver function, liver enzymes, alpha fetoprotein (AFP) and viral markers. Moreover, triphasic pelviabdominal CT will be performed .
4. Blood samples will be collected for ATG10 AND IL6 genotyping.

5. Genetic polymorphisms of ATG10 AND IL6 will be detected by real time polymerase chain reaction (RT-PCR).

   • Five mls of whole blood will be collected
   • Extraction of genomic DNA from blood samples by DNA extraction kit.
   • DNA qualification will be performed by Nano drop.
   • Genotyping will be done by allelic discrimination using Taqman assays specific for each polymorphism.
   • Assays will be done according to manufacturer protocol using real time PCR machine.
6. Appropriate statistical tests will be conducted to evaluate the significance of the results.

7. Results, conclusion, discussion and recommendations will be given. Ethical Issue

   • Informed consent will be signed by all eligible patients before enrolling in the study.
   • All patients' data will be confidential.

Efficacy and Safety outcomes:

1. Target lesions response will be measured according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) Complete response, Partial response, Progressive disease and Stable disease.
2. The appropriate dose of sorafenib will be determined individually based on the patient tolerability.
3. Follow up will be performed for detection of tumor size using triphasic CT scan as a measure of efficacy. Moreover, all patients will be reevaluated for CBC,AFP, liver and kidney functions, in the follow up visit, to detect incidence of any adverse effects.
4. Patients will be asked for any side effects such as (diarrhea, anorexia, nausea, vomiting).
5. Patients will be followed for progression-free survival after receiving soarfenib.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • El-Dakahelia
    • Mansoura, El-Dakahelia, Egypt, 31527
      • Mansoura University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. A diagnosed HCC patient.
2. Child-pugh class A.
3. Performance status 1-2 (ECOG scale)
4. Laboratory investigation : Hemoglobin ≥8.5 mg\dl, INR ≤2.3 ,Albumin≥2.8g\dl, ALT and AST ≤ 3 times the ULN
5. Age ≥20 years.

Exclusion Criteria:

1. Patients refused to sign the written consent.
2. Age > 75 years.
3. Renal failure requiring hemo- or peritoneal dialysis
4. History of cardiac disease
5. Active clinically serious infections
6. Known history of human immunodeficiency virus (HIV) infection
7. Pregnant female
8. Child-pugh class B and C.
9. Performance status 3 or 4.
10. Patient who are indicated for surgical resection or liver transplant (MDT).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sorafenib group; 100 patients diagnosed with HCC for whom Sorafenib therapy is prescribed (400 mg twice daily) or (200mg twice daily), will be recruited from Mansoura University Hospital, Mansoura, Egypt.	Drug: Sorafenib Tablets; Sorafenib Tablets (200 -400 mg) twice daily; Other Names: Nexavar

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ATG10 genotyping	Gene polymorphism	6 months
IL6 genotyping	Gene polymorphism	6 months
Safety Outcomes	Incidence of side effects such as (diarrhea, anorexia, nausea, vomiting	6 months

Collaborators and Investigators

• Sponsor: Damanhour University
• Collaborators: Mransoura University
• Investigators: Study Director: Noha El bassiouny, Lecturer, Damanhour University; Study Chair: Rehab H Werida, Ass. Prof., Damanhour University

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Actual): February 21, 2024
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: September 3, 2023
• First Submitted That Met QC Criteria: September 3, 2023
• First Posted (Actual): September 11, 2023

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 9, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Polymorphism; IL6; Genotyping; ATG10
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: sorafenib In Egyptian Patients

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No