Clinical trial NCT05291338: Pharmacogenetic Study in Hepatocellular Carcinoma Patients.
Official title: Pharmacogenetic Study in Hepatocellular Carcinoma Patients Underwent TACE
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatocellular Carcinoma
Keywords: ANG-2
IL28B
genetic polymorphisms
Lead sponsor: Damanhour University
Sponsor class: OTHER
First posted: 2022-03-22
Enrollment: 107
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Egyptian HCC patients on doxorubicin and lipiodol treatment

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Angiopoietin (ANG-2) rs55633437.
timeFrame: 1 month
measure: Interleukin 28 B (IL28B) rs12979860.
timeFrame: 1 month
Secondary outcomes:
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Ain Shams University hepatoma group, EL Demerdash Hospital, Cairo, Egypt.
Study officials:
affiliation: Damanhour University
name: Rehab H Werida, Ass Prof.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.