Study of CYP2C19 and ALDH3A1 Polymorphisms in Breast Cancer Patients

October 8, 2020 updated by: Amira Bisher,PhD, Damanhour University

Pharmacogenetic Risk Factors of Doxorubicin-Cyclophosphamide Chemotherapy Related Toxicities in Breast Cancer Patients

Genetic polymorphisms of metabolic enzymes may influence the metabolism of Doxorubicin-Cyclophosphamide regimen in breast cancer patients.

the investigators want to

  1. evaluate the frequency or incidence of the genetic polymorphisms of CYP2C19 and ALDH3A1 in breast cancer patients, and
  2. analyze the association between the genetic polymorphisms of CYP2C19 and ALDH3A1 and toxicities in breast cancer patients treated by Doxorubicin-Cyclophosphamide regimen therapy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Breast cancer refers to the erratic growth and proliferation of cells that originate in the breast tissue, most commonly from the inner lining of milk ducts (ductal cancers) or the lobules that supply the ducts with milk (lobular cancers). Breast cancer is about 100 times more common in women than in men, although males tend to have poorer outcomes due to delays in diagnosis. Alteration in hormonal level and Family history of breast cancer are risk factors for breast cancer.

The classic symptom for breast cancer is a lump found in the breast or armpit. Doing monthly breast self-exam (BSE) is a great way to be familiar with the breasts' texture, cyclical changes, size, and skin condition. Breast cancer is usually diagnosed by biopsy of nodule detected by mammogram or by palpitation.

Today there are so many approaches, which can be made for the treatment of breast cancer such as surgery, radiation therapy, chemotherapy, hormonal therapy and recently nanotechnology and gene therapy. Chemotherapy is the use of anti-cancer drugs to treat cancerous cells. The differences in patients' response to the same medication, toxicity included, are one of the major problems in breast cancer treatment.

Chemotherapy toxicity makes a significant clinical problem due to decreased quality of life, prolongation of treatment and reinforcement of negative emotions associated with therapy. Four cycles of doxorubicin and cyclophosphamide (AC) chemotherapy regimen has become a standard regimen. No chemotherapy regimen administered for four cycles has proven to be superior to AC. The undeniable advantage of this therapy scheme is low cost of treatment, its proven efficacy and mostly acceptable toxicity. Hematological (neutropenia and anemia) and gastrointestinal (nausea, vomiting and mucositis) toxicities are common in patients treated with AC regimen.

Doxorubicin is metabolized by the CBR (carbonyl reductase) enzymes to its active component. Similarly cyclophosphamide, the cell cycle nonspecific prodrug, requires activation by a number of different cytochrome P450 enzymes, mainly of CYP2C family. The transport systems are also crucial for the treatment outcome, as both importers and exporters are responsible for the cellular drugs' concentration. It is expected that any variation that affects metabolic enzymes and transporter activity would be reflected in not only the response to treatment, but also in the development of drug-related toxicity. Each of these enzymes and transporter genes is known to exhibit a degree of genetic variation, characterized by single nucleotide polymorphisms (SNPs). In particular, there have been few investigations of the possible influence of variations in the genes encoding transporters and drug metabolizing enzymes relevant for the two drugs.

Pharmacogenomic analysis offers the promise that personalized regimens may be identified for individuals who might have more favorable outcomes with certain chemotherapies. Specifically, because genetic variation in metabolic enzymes is one determinant of drug concentration, pharmacogenomics has been proposed as an approach to tailor drug choice or dose to optimize efficacy and reduce toxicity of cancer treatments.

Study Type

Observational

Enrollment (Anticipated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Hoda Salem, Ass. Prof
  • Phone Number: 00201000007613
  • Email: hsalem@ut.edu.sa

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

all breast cancer patients receiving either adjuvant or neoadjuvant therapy in National Cancer Institute

Description

Inclusion Criteria:

  1. Confirmed diagnosis of breast cancer.
  2. Age ranging from 18 to 75 years old female.
  3. Patients will take Doxorubicin-Cyclophosphamide regimen as chemotherapy treatment.

Exclusion Criteria:

  1. Any other malignancy.
  2. Previous treatment for metastatic disease.
  3. Pregnancy or breastfeeding female.
  4. Inadequate bone marrow and cardiac function.
  5. Serious or uncontrolled medical conditions.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The frequency of the genetic polymorphisms of CYP2C19 in breast cancer patients
Time Frame: Up to 24 weeks
the blood samples will be DNA extracted using DNA extraction kit then single nucleotide polymorphisms of CYP2C19 gene will be detected by real time PCR
Up to 24 weeks
The frequency of the genetic polymorphisms of ALDH3A1 in breast cancer patients
Time Frame: Up to 24 weeks
the blood samples will be DNA extracted by DNA extraction kit then single nucleotide polymorphisms of ALDH3A1 gene will be detected by real time PCR
Up to 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between genetic polymorphisms of CYP2C19 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
Time Frame: up to 24 weeks
the blood samples will be DNA extracted using DNA extraction kit then single nucleotide polymorphisms of CYP2C19 gene will be detected by real time PCR
up to 24 weeks
Correlation between genetic polymorphisms of ALDH3A1 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
Time Frame: up to 24 weeks
the blood samples will be DNA extracted by DNA extraction kit then single nucleotide polymorphisms of ALDH3A1 gene will be detected by real time PCR
up to 24 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Damanhour University

Collaborators

Al-Azhar University
National Cancer Institute, Egypt

Investigators

  • Study Director: Hoda Salem, Ass. Prof, faculty of pharmacy, Al-Azhar University
  • Study Chair: Marwa Nabeel, Ass. Prof, National Cancer Institute-Cairo University
  • Principal Investigator: Amira Bisheer, PhD, faculty of pharmacy, Damanhour University
  • Principal Investigator: Esraa Khaled, B. Pharm, faculty of pharmacy, Al-Azhar University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

October 15, 2020

Primary Completion (Anticipated)

December 15, 2020

Study Completion (Anticipated)

January 15, 2021

Study Registration Dates

First Submitted

April 22, 2020

First Submitted That Met QC Criteria

October 8, 2020

First Posted (Actual)

October 9, 2020

Study Record Updates

Last Update Posted (Actual)

October 9, 2020

Last Update Submitted That Met QC Criteria

October 8, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201819010.4

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer Patients

Clinical Trials on polymorphism analysis

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Myanmar

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe