Pharmacogenetic Study in Hepatocellular Carcinoma Patients.

Pharmacogenetic Study in Hepatocellular Carcinoma Patients Underwent TACE

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

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: 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 116 patients. Efficacy and Safety

1. 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.

2. Repeated TACE sessions will be planned individually based on the tumor response to the treatment protocol.
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, 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 (myelosuppression, anorexia, nausea, vomiting, and/or alopecia).
5. Patients will be followed for progression-free survival after receiving TACE.

Method & Proposal Steps

1. Approval will be obtained from Research Ethics Committee of Faculty of Pharmacy, Damanhour University.
2. Patients will be recruited from Ain Shams University hepatoma group, EL Demerdash Hospital, Cairo, Egypt.
3. 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.
4. Serum samples will be collected for ANG-2 and IL28B genotyping.

5. 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.
6. 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.
7. Appropriate statistical tests will be conducted to evaluate the significance of the results.
8. Results, conclusion, discussion and recommendations will be given.

• Study Type: Observational
• Enrollment (Actual): 107

Contacts and Locations

• Study Contact: Name: Radwa Hagag, Lecturer; Email: dr_mradwan@yahoo.com

Study Locations

• Egypt
  • Cairo, Egypt
    • Ain Shams University hepatoma group, EL Demerdash Hospital, Cairo, Egypt.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Egyptian HCC patients on doxorubicin and lipiodol treatment

Description

Inclusion Criteria:

• Eligible patients should fulfill the following criteria:

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

Exclusion Criteria:

• Patient will be excluded for any of the following:

  1. Patients refused to sign the written consent.
  2. Age > 75 years.
  3. The presence of major portal vein thrombosis.
  4. Extrahepatic metastases.
  5. Hepatic encephalopathy.
  6. Current infection.
  7. Gastrointestinal bleeding within a month.
  8. Uncontrolled ascites.
  9. 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.
  10. Patients with other types of malignancy, advanced organ failure, and advanced medical co-morbidity.
  11. Pregnant females.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HCC patients; 116 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Angiopoietin (ANG-2) rs55633437.	Gene	1 month
Interleukin 28 B (IL28B) rs12979860.	Gene	1 month

Collaborators and Investigators

• Sponsor: Rehab Werida
• Investigators: Study Director: Rehab H Werida, Ass Prof., Damanhour University

Publications and helpful links

General Publications

• Rashed WM, Kandeil MAM, Mahmoud MO, Ezzat S. Hepatocellular Carcinoma (HCC) in Egypt: A comprehensive overview. J Egypt Natl Canc Inst. 2020 Jan 16;32(1):5. doi: 10.1186/s43046-020-0016-x.
• Marisi G, Petracci E, Raimondi F, Faloppi L, Foschi FG, Lauletta G, Iavarone M, Canale M, Valgiusti M, Neri LM, Ulivi P, Orsi G, Rovesti G, Vukotic R, Conti F, Cucchetti A, Ercolani G, Andrikou K, Cascinu S, Scartozzi M, Casadei-Gardini A. ANGPT2 and NOS3 Polymorphisms and Clinical Outcome in Advanced Hepatocellular Carcinoma Patients Receiving Sorafenib. Cancers (Basel). 2019 Jul 20;11(7):1023. doi: 10.3390/cancers11071023.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): April 1, 2023

Study Registration Dates

• First Submitted: March 12, 2022
• First Submitted That Met QC Criteria: March 12, 2022
• First Posted (Actual): March 22, 2022

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: IL28B; genetic polymorphisms; ANG-2
• 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; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin; Ethiodized Oil
• Other Study ID Numbers: genetic in hepatic cancer

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