Breast Cancer PatientsNCT04581967
Study of CYP2C19 and ALDH3A1 Polymorphisms in Breast Cancer Patients
An observational study of Breast Cancer Patients, run by Damanhour University at 1 site in Egypt.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years, women only
- Conditions the study is for
- Breast Cancer Patients
- What is being tested?
- polymorphism analysis and Doxorubicin-Cyclophosphamide regimen
- Type of treatment
- Injection or infusion
- How many people
- 100 participants
- Where
- 1 siteEgypt
- Study dates
- 15 Oct 2020to 15 Jan 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: all breast cancer patients receiving either adjuvant or neoadjuvant therapy in National Cancer Institute
Who may be able to join
- Confirmed diagnosis of breast cancer.
- Age ranging from 18 to 75 years old female.
- Patients will take Doxorubicin-Cyclophosphamide regimen as chemotherapy treatment.
Who cannot join
- Any other malignancy.
- Previous treatment for metastatic disease.
- Pregnancy or breastfeeding female.
- Inadequate bone marrow and cardiac function.
- Serious or uncontrolled medical conditions.
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
National Cancer Institute
Cairo, 11796
Marwa Nabeel, Ass. Prof, 00201278511006, Marwa_nabil_25@yahoo.com
Esraa Khaled, B. Pharm, 00201009956676, Esraakhaled11@gmail.com
About this study
Official title: 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
- evaluate the frequency or incidence of the genetic polymorphisms of CYP2C19 and ALDH3A1 in breast cancer patients, and
- analyze the association between the genetic polymorphisms of CYP2C19 and ALDH3A1 and toxicities in breast cancer patients treated by Doxorubicin-Cyclophosphamide regimen therapy.
Read the 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.
- Conditions
- Breast Cancer Patients
- Being tested
- polymorphism analysis, Doxorubicin-Cyclophosphamide regimen
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
polymorphism analysisGenetic
Also called single nucleotide polymorphism
- 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.
Doxorubicin-Cyclophosphamide regimenDrug
Also called chemotherapy treatment
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
The frequency of the genetic polymorphisms of CYP2C19 in breast cancer patients
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
Measured: Up to 24 weeks
The frequency of the genetic polymorphisms of ALDH3A1 in breast cancer patients
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
Measured: Up to 24 weeks
Secondary outcomes (2)
Correlation between genetic polymorphisms of CYP2C19 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
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
Measured: up to 24 weeks
Correlation between genetic polymorphisms of ALDH3A1 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
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
Measured: up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Oct 2020
- Study start15 Oct 2020 (estimated)
- Primary completion15 Dec 2020 (estimated)
- Study completion15 Jan 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer PatientsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Damanhour University
- Sponsor type
- University, hospital or other
- Collaborators
- Al-Azhar University, National Cancer Institute, Egypt
- Responsible party
- Principal investigator, Amira Bisher,PhD, Damanhour University
- Investigators
- Hoda Salem, Ass. Prof, Study director, faculty of pharmacy, Al-Azhar universityMarwa Nabeel, Ass. Prof, Study chair, National Cancer Institute-Cairo UniversityAmira Bisheer, PhD, Principal investigator, faculty of pharmacy, Damanhour UniversityEsraa Khaled, B. Pharm, Principal investigator, faculty of pharmacy, Al-Azhar University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04581967
- Sponsor's protocol ID
- 201819010.4
- Status last verified
- Aug 2020
- First submitted
- 22 Apr 2020
- Last updated
- 9 Oct 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 22247839Tecza 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.
PubMed 29507678Jones 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.
PubMed 17135639Montoya 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.
PubMed 23629563Bray 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.
PubMed 20179710Zhou 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.
PubMed 29242966
Study at a glance
From the registry record, last updated by the sponsor on 9 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetic Risk Factors of Doxorubicin-Cyclophosphamide Chemotherapy Related Toxicities in Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT04581967
- Acronym / sponsor ID
- 201819010.4
- Conditions
- Breast Cancer Patients
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Damanhour UniversityUniversity, hospital or other
- Collaborators
- Al-Azhar University, National Cancer Institute, Egypt
- Study start
- 15 Oct 2020 (estimated)
- Primary completion
- 15 Dec 2020 (estimated)
- Study completion
- 15 Jan 2021 (estimated)
- First posted
- 9 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Genetic polymorphisms of metabolic enzymes may influence the metabolism of Doxorubicin-Cyclophosphamide regimen in breast cancer patients.
the investigators want to
- evaluate the frequency or incidence of the genetic polymorphisms of CYP2C19 and ALDH3A1 in breast cancer patients, and
- 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
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- all breast cancer patients receiving either adjuvant or neoadjuvant therapy in National Cancer Institute
Key inclusion criteria (3 listed)
- Confirmed diagnosis of breast cancer.
- Age ranging from 18 to 75 years old female.
- Patients will take Doxorubicin-Cyclophosphamide regimen as chemotherapy treatment.
Key exclusion criteria (5 listed)
- Any other malignancy.
- Previous treatment for metastatic disease.
- Pregnancy or breastfeeding female.
- Inadequate bone marrow and cardiac function.
- Serious or uncontrolled medical conditions.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| polymorphism analysisAlso: single nucleotide polymorphism* 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. | Genetic | – |
| Doxorubicin-Cyclophosphamide regimenAlso: chemotherapy treatmentTreatment 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. | Drug | – |
Primary outcome
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
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
2 secondary outcomes
Correlation between genetic polymorphisms of CYP2C19 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
Time frame: up to 24 weeks
Correlation between genetic polymorphisms of ALDH3A1 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
Time frame: up to 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Oct 2020.
- Background: PubMed 22247839Sharma 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.
- Background: PubMed 29507678Tecza 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.
- Background: PubMed 17135639Jones 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.
- Background: PubMed 23629563Montoya 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.
- Background: PubMed 20179710Bray 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.
- Background: PubMed 29242966Zhou 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hoda Salem, Ass. Prof study director
faculty of pharmacy, Al-Azhar university
Marwa Nabeel, Ass. Prof study chair
National Cancer Institute-Cairo University
Amira Bisheer, PhD principal investigator
faculty of pharmacy, Damanhour University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Breast Cancer Patients, run by Damanhour University at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 9 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hoda Salem, Ass. Prof (00201000007613, hsalem@ut.edu.sa), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The frequency of the genetic polymorphisms of CYP2C19 in breast cancer patients (time frame: Up to 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04581967, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2020.