Pharmacogenetic Study in Hepatocellular Carcinoma Patients.

Sponsor

Rehab Werida (Other)

Overall Status

Recruiting

CT.gov ID

NCT05291338

Collaborator

(none)

100

Enrollment

Location

Anticipated Duration (Months)

7.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

evaluate the prognostic value of genetic polymorphisms in HCC Egyptian patients undergoing TACE using lipiodol and doxorubicin.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Doxorubicin Drug: Lipiodol

Detailed Description

Research Objectives This study aims to determine the predictive effect of ANG-2 and IL28B genetic polymorphisms in safety and efficacy of doxorubicin and lipiodol used for the treatment of Egyptian HCC patients. Moreover, this study will determine the association between genetic polymorphisms of ANG-2 and IL28B with HCC severity.

Patients & Methods Study design Our study is a prospective study for HCC patients undergoing TACE of doxorubicin and lipiodol.

Sample Size Based on previous published incidence of gene it will be at least 100 patients. Efficacy and Safety

Target lesions response will be measured according to modified Response Evaluation

Criteria in Solid Tumors (RECIST) to (15):

Complete response, Partial response, Progressive disease and Stable disease.

Repeated TACE sessions will be planned individually based on the tumor response to the treatment protocol.
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, liver and kidney functions, in the follow up visit, to detect incidence of any adverse effects.
Patients will be asked for any side effects such as (myelosuppression, anorexia, nausea, vomiting, and/or alopecia).
Patients will be followed for progression-free survival after receiving TACE.

Method & Proposal Steps

Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy, Damanhour University.
Patients will be recruited from Ain Shams University hepatoma group, EL Demerdash Hospital, Cairo, Egypt.
At baseline and follow up visits after TACE, 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 before and after TACE.
Serum samples will be collected for ANG-2 and IL28B genotyping.
Genetic polymorphisms of ANG-2 and IL28B will be detected by real time polymerase chain reaction (RT-PCR).

Five mls of whole blood will be collected then separation of plasma will be performed.
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.

All patients will receive lipiodol and doxorubicin during TACE. Doxorubicin dose will differ among patients according to tumor size, patient condition, patient's laboratory data and presence of hepatic arteriovenous fistula.
Appropriate statistical tests will be conducted to evaluate the significance of the results.
Results, conclusion, discussion and recommendations will be given.

Study Design

Study Type:

Observational

Anticipated Enrollment :

100 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Pharmacogenetic Study in Hepatocellular Carcinoma Patients Underwent TACE

Actual Study Start Date :

Jan 1, 2022

Anticipated Primary Completion Date :

Jan 31, 2023

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
HCC patients 100 hepatocellular carcinoma patients underwent TACE	Drug: Doxorubicin no optimal dosage of doxorubicin in TACE procedures (ranging from 30 to 75 mg/m2 up to a maximum of 150 mg/m2 ) according to tumor size Other Names: Adriamycin Drug: Lipiodol Lipiodol dose should be over 5 ml if tumor diameter is less than 5 cm, and the maximum dose will be 10 ml when the tumor develops to more than 5 cm in diameter. Other Names: ethiodized oil

Arm

Intervention/Treatment

HCC patients

100 hepatocellular carcinoma patients underwent TACE

Drug: Doxorubicin

no optimal dosage of doxorubicin in TACE procedures (ranging from 30 to 75 mg/m2 up to a maximum of 150 mg/m2 ) according to tumor size

Other Names:

Adriamycin

Drug: Lipiodol

Lipiodol dose should be over 5 ml if tumor diameter is less than 5 cm, and the maximum dose will be 10 ml when the tumor develops to more than 5 cm in diameter.

Other Names:

ethiodized oil

Outcome Measures

Primary Outcome Measures

Angiopoietin (ANG-2) rs55633437. [1 month]
Gene
Interleukin 28 B (IL28B) rs12979860. [1 month]
Gene

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 75 Years

Sexes Eligible for Study:

All

Inclusion Criteria:

Eligible patients should fulfill the following criteria:

A diagnosed HCC patient.
Age ≥20 years.
Patients with adequate organ function.
HCC not eligible for curative measures (radiofrequency, microwave and surgery).

Exclusion Criteria:

Patient will be excluded for any of the following:

Patients refused to sign the written consent.
Age > 75 years.
The presence of major portal vein thrombosis.
Extrahepatic metastases.
Hepatic encephalopathy.
Current infection.
Gastrointestinal bleeding within a month.
Uncontrolled ascites.
Serum bilirubin > 3.0 mg/dl, serum albumin < 2.8 g/dl, serum creatinine concentration > 1.5 mg/dl, white blood cell counts < 3,000/mm3 and platelet counts < 30,000/mm3.
Patients with other types of malignancy, advanced organ failure, and advanced medical co-morbidity.
Pregnant females.