Clinical trial NCT06030895: Sorafenib In Egyptian Patients With Hepatocellular Carcinoma.
Official title: Pharmacogenetic Study of Sorafenib In Egyptian Patients With Hepatocellular Carcinoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatocellular Carcinoma
Keywords: ATG10
IL6
Genotyping
Safety
Efficacy
Polymorphism
Lead sponsor: Damanhour University
Sponsor class: OTHER
First posted: 2023-09-11
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 100 hepatocellular carcinoma patients
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: ATG10 genotyping
timeFrame: 6 months
measure: IL6 genotyping
timeFrame: 6 months
measure: Safety Outcomes
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Mansoura
country: Egypt
facility: Mansoura University Hospital
state: El-Dakahelia
Study officials:
affiliation: Damanhour University
name: Rehab H Werida, Ass. Prof.
role: STUDY_CHAIR
affiliation: Damanhour University
name: Noha El bassiouny, Lecturer
role: STUDY_DIRECTOR
References: