Study of CYP2C19 and ALDH3A1 Polymorphisms in Breast Cancer Patients

NCT ID: NCT04581967

Last Updated: 2020-10-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

100 participants

Study Classification

OBSERVATIONAL

Study Start Date

2020-10-15

Study Completion Date

2021-01-15

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Breast Cancer Patients

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

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polymorphism analysis

* DNA will be purified from whole blood samples by commercial DNA isolation kits.
* Genotyping and genetic polymorphism detection for some metabolic enzymes genes will be performed by real time PCR.

Intervention Type GENETIC

Doxorubicin-Cyclophosphamide regimen

Treatment with a combination of Doxorubicin and Cyclophosphamide, This regimen comprises 60 mg/m² Doxorubicin and 600 mg/m² Cyclophosphamide administered intravenously on day 1 of each 21-day cycle, and repeated for a total of four cycles.

Intervention Type DRUG

Other Intervention Names

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single nucleotide polymorphism chemotherapy treatment

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Al-Azhar University

OTHER

Sponsor Role collaborator

National Cancer Institute, Egypt

OTHER

Sponsor Role collaborator

Damanhour University

OTHER

Sponsor Role lead

Responsible Party

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Amira Bisher,PhD

principal investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Hoda Salem, Ass. Prof

Role: STUDY_DIRECTOR

faculty of pharmacy, Al-Azhar university

Marwa Nabeel, Ass. Prof

Role: STUDY_CHAIR

National Cancer Institute-Cairo University

Amira Bisheer, PhD

Role: PRINCIPAL_INVESTIGATOR

faculty of pharmacy, Damanhour University

Esraa Khaled, B. Pharm

Role: PRINCIPAL_INVESTIGATOR

faculty of pharmacy, Al-Azhar University

Locations

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National Cancer Institute

Cairo, , Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Hoda Salem, Ass. Prof

Role: CONTACT

00201000007613

Esraa Khaled, B. Pharm

Role: CONTACT

00201009956676

Facility Contacts

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Marwa Nabeel, Ass. Prof

Role: primary

00201278511006

Esraa Khaled, B. Pharm

Role: backup

00201009956676

References

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Sharma GN, Dave R, Sanadya J, Sharma P, Sharma KK. Various types and management of breast cancer: an overview. J Adv Pharm Technol Res. 2010 Apr;1(2):109-26.

Reference Type BACKGROUND
PMID: 22247839 (View on PubMed)

Tecza K, Pamula-Pilat J, Lanuszewska J, Butkiewicz D, Grzybowska E. Pharmacogenetics of toxicity of 5-fluorouracil, doxorubicin and cyclophosphamide chemotherapy in breast cancer patients. Oncotarget. 2018 Jan 10;9(10):9114-9136. doi: 10.18632/oncotarget.24148. eCollection 2018 Feb 6.

Reference Type BACKGROUND
PMID: 29507678 (View on PubMed)

Jones SE, Savin MA, Holmes FA, O'Shaughnessy JA, Blum JL, Vukelja S, McIntyre KJ, Pippen JE, Bordelon JH, Kirby R, Sandbach J, Hyman WJ, Khandelwal P, Negron AG, Richards DA, Anthony SP, Mennel RG, Boehm KA, Meyer WG, Asmar L. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7. doi: 10.1200/JCO.2006.06.5391.

Reference Type BACKGROUND
PMID: 17135639 (View on PubMed)

Montoya JE, Luna HG, Morelos AB, Catedral MM, Lava AL, Amparo JR, Cristal-Luna GR. Association of creatinine clearance with neutropenia in breast cancer patients undergoing chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide (FAC). Med J Malaysia. 2013 Apr;68(2):153-6.

Reference Type BACKGROUND
PMID: 23629563 (View on PubMed)

Bray J, Sludden J, Griffin MJ, Cole M, Verrill M, Jamieson D, Boddy AV. Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide. Br J Cancer. 2010 Mar 16;102(6):1003-9. doi: 10.1038/sj.bjc.6605587. Epub 2010 Feb 23.

Reference Type BACKGROUND
PMID: 20179710 (View on PubMed)

Zhou X, Qiao G, Wang X, Song Q, Morse MA, Hobeika A, Gwin WR, Ren J, Lyerly HK. CYP1A1 genetic polymorphism is a promising predictor to improve chemotherapy effects in patients with metastatic breast cancer treated with docetaxel plus thiotepa vs. docetaxel plus capecitabine. Cancer Chemother Pharmacol. 2018 Feb;81(2):365-372. doi: 10.1007/s00280-017-3500-9. Epub 2017 Dec 14.

Reference Type BACKGROUND
PMID: 29242966 (View on PubMed)

Other Identifiers

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201819010.4

Identifier Type: -

Identifier Source: org_study_id

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