Breast Cancer PatientsNCT04654195
Study of ABCB1,SLC22A16 Drug Transporter Genes and Doxorubicin and Cyclophosphamide Toxicity in Brest Cancer Patient
An observational study of Breast Cancer Patients, run by Damanhour University at 1 site in Egypt.
Trial summary
polymorphisms of drug transporter genes may influence of Doxorubicin-Cyclophosphamide toxicity in breast cancer patients. the investigators want to evaluate the association between associations between genetic polymorphisms of ABCB1,SLC22A16 Genes and Toxicity of Doxorubicin and Cyclophosphamide Chemotherapy in Breast… Read more about this study
- Who is it for?
- Ages 20 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
- 1 Dec 2020to 1 Feb 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 20 to 75 years
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: all breast cancer females reciving (Ac regimen) at El-hosien University Hospital
Who may be able to join
- women who has confirmed diagnosis of breast cancer.
- patient who will be treated with cyclophosphamide and doxorubicin(AC) regimen only .
- patient take drug regimen for first time.
Who cannot join
- 1. Patients with metastatic disease and with other previous tumors were excluded from this study 2. Pregnant or nursing female. 3. The patients who were diagnosed with cardiovascular disease or with low left ventricular ejection fraction.
- 4 .patients who had benign breast cancers, or had no clinical pathological information
Trial locations and contacts
1 site in 1 country.
Egypt1 site, 1 recruiting
- Recruiting
Elhussien University Hospital
Cairo, 11651
sanaa mohsen, B.pharm, 00201117480060, sanaamohsen9087@gmail.com
wael elshishtawy, Ass.prof, 00201119888618
About this study
Official title: Associations Between Genetic Polymorphisms of Drug Transporter Genes and Toxicity of Doxorubicin and Cyclophosphamide Chemotherapy in Breast Cancer Patients
polymorphisms of drug transporter genes may influence of Doxorubicin-Cyclophosphamide toxicity in breast cancer patients.
the investigators want to
evaluate the association between associations between genetic polymorphisms of ABCB1,SLC22A16 Genes and Toxicity of Doxorubicin and Cyclophosphamide Chemotherapy in Breast Cancer Patients treated by Doxorubicin-Cyclophosphamide regimen therapy
Read the detailed description
breast cancer is the most common cancer diagnosed in women .Breast cancer can occur in both men and women, but it's far more common in women.
The etiology of breast cancer possesses a multifactorial origin , showing as risk factors reproductive age, early menarche, late menopause, nulli parity, exogenous hormones ,smoking, obesity, diet, alcohol consumption, physical inactivity, and genetic and environmental factors(1).
Chemotherapy combination usually used in treat breast cancer specially cyclophosphamide which is alkylating agent and doxorubicin which is cytotoxic drug.
Doxorubicin entry to the cell is facilitated by the solute importer SLC22A16,the efflux of AC drugs uses several ATP-binding cassette transporters (ABC),( ABCB1, ABCC1, ABCC2, ABCG2)(2),(7).
Most chemotherapeutic agents are not specific against neoplastic cells , also affecting normal cells. Which result in a wide range of adverse reactions in virtually all tissue of body. Unfortunately, chemotherapy-induced toxicities are commonly affecting cancer patients with various intensity, and could be the reason for treatment delays and significantly lowered quality of life. Hematological and gastrointestinal toxicities are common in patients treated with cyclophosphamide and doxorubicin(3).
Extremely high proliferative capacity of hematopoietic system makes it the collateral target for chemotherapeutic agents. Chemotherapy-induced neutropenia are , because of the high susceptibility of neutrophil lineage to cytotoxic effects of cancer treatment. The drug-induced destruction of neutrophil precursors in bone marrow is the main cause of those symptoms. Decrease in neutrophil count is managed by the dose reduction and delays that decrease the dose intensity, where is maintaining the dose is important for favorable response to treatment(3). Another frequent and serious myelotoxic symptom in breast cancer chemotherapy is anemia. This condition may emerge from the disease itself, but the effect of concomitant administration of cytotoxic drugs is also the cause of drop in the hemoglobin level. Anemia has deleterious effect on patients' quality of life as well as on the treatment response. The suspected causes include blood loss, reduced or impaired erythrocytes production and high rate of red blood cells destruction or their reduced survival(4).
Chemotherapy-induced nausea and vomiting (CINV) is a common severe side effect for cancer patients undergoing emetic chemotherapy. The complete pathophysiology of CINV is not known but gastrointestinal (GI) side effects associated with anticancer chemotherapy are traditionally thought to be attributable to mucosal damage.
Nausea is complex in nature and probably depending on more than one etiological factor . Different pathways have been identified for acute and delayed CINV Also, nausea and vomiting can result in anorexia, decreased performance status, metabolic imbalance, wound dehiscence, esophageal tears and nutritional deficiency(5).
In the study we will focuse on the analysis of the relations between the polymorphic variants in some drug transporter genes with known or potential role in the AC-induced toxicity. Single nucleotide polymorphisms will analyzed in genes encoding proteins Involved in AC drug transport
- 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.
.1-The frequency of the genetic polymorphisms of ABCB1 in breast cancer patien
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 week
The frequency of the genetic polymorphisms of SLC22A16 in breast cancer patients
the blood samples will be DNA extracted by DNA extraction kit then single nucleotide polymorphisms of SL22A16 gene will be detected by real time PCR
Measured: up to 24 week
Secondary outcomes (2)
Correlation between genetic polymorphisms of ABCB1 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
the blood samples will be DNA extracted using DNA extraction kit then single nucleotide polymorphisms of ABCB1 gene will be detected by real time PCR
Measured: up to 24 week
Correlation between genetic polymorphisms of SLC22A16 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
the blood samples will be DNA extracted by DNA extraction kit then single nucleotide polymorphisms of SL22A16 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 posted4 Dec 2020
- Study start1 Dec 2020 (estimated)
- Primary completion1 Feb 2021 (estimated)
- Study completion1 Feb 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)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
- Responsible party
- Sponsor
- Investigators
- Hoda salem, Ass.prof, Study director, Faculty of pharmacy Al-Azhar University for GirlsWael helmy, Ass.prof, Principal investigator, Faculty of medicine Al-Azhar University for BoysAmira bisheer, PhD, Principal investigator, faculty of pharmacy ,Damanhour Universitysanaa mohsen, B.pharm, Principal investigator, faculty of pharmacy,Al-Azhar University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04654195
- Sponsor's protocol ID
- 0000012
- Status last verified
- Jul 2020
- First submitted
- 29 Apr 2020
- Last updated
- 4 Dec 2020
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 29507678Ludovini V, Antognelli C, Rulli A, Foglietta J, Pistola L, Eliana R, Floriani I, Nocentini G, Tofanetti FR, Piattoni S, Minenza E, Talesa VN, Sidoni A, Tonato M, Crino L, Gori S. Influence of chemotherapeutic drug-related gene polymorphisms on toxicity and survival of early breast cancer patients receiving adjuvant chemotherapy. BMC Cancer. 2017 Jul 26;17(1):502. doi: 10.1186/s12885-017-3483-2.
PubMed 287471563-U.S. department of health and human services(2017): Common Terminology Criteria for Adverse Events (CTCAE),National Cancer Institute ,2017,pp(4-6 ) ,pp(24-44).
Islam MS, Islam MS, Parvin S, Ahmed MU, Bin Sayeed MS, Uddin MM, Hussain SM, Hasnat A. Effect of GSTP1 and ABCC4 gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-5-fluorouracil-based chemotherapy in Bangladeshi breast cancer patients. Tumour Biol. 2015 Jul;36(7):5451-7. doi: 10.1007/s13277-015-3211-y. Epub 2015 Feb 13.
PubMed 25677905
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Associations Between Genetic Polymorphisms of Drug Transporter Genes and Toxicity of Doxorubicin and Cyclophosphamide Chemotherapy in Breast Cancer Patients
- ClinicalTrials.gov ID
- NCT04654195
- Acronym / sponsor ID
- 0000012
- 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
- Study start
- 1 Dec 2020 (estimated)
- Primary completion
- 1 Feb 2021 (estimated)
- Study completion
- 1 Feb 2021 (estimated)
- First posted
- 4 Dec 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.
polymorphisms of drug transporter genes may influence of Doxorubicin-Cyclophosphamide toxicity in breast cancer patients.
the investigators want to
evaluate the association between associations between genetic polymorphisms of ABCB1,SLC22A16 Genes and Toxicity of Doxorubicin and Cyclophosphamide Chemotherapy in Breast Cancer Patients treated by Doxorubicin-Cyclophosphamide regimen therapy
Detailed description
breast cancer is the most common cancer diagnosed in women .Breast cancer can occur in both men and women, but it's far more common in women.
The etiology of breast cancer possesses a multifactorial origin , showing as risk factors reproductive age, early menarche, late menopause, nulli parity, exogenous hormones ,smoking, obesity, diet, alcohol consumption, physical inactivity, and genetic and environmental factors(1).
Chemotherapy combination usually used in treat breast cancer specially cyclophosphamide which is alkylating agent and doxorubicin which is cytotoxic drug.
Doxorubicin entry to the cell is facilitated by the solute importer SLC22A16,the efflux of AC drugs uses several ATP-binding cassette transporters (ABC),( ABCB1, ABCC1, ABCC2, ABCG2)(2),(7).
Most chemotherapeutic agents are not specific against neoplastic cells , also affecting normal cells. Which result in a wide range of adverse reactions in virtually all tissue of body. Unfortunately, chemotherapy-induced toxicities are commonly affecting cancer patients with various intensity, and could be the reason for treatment delays and significantly lowered quality of life. Hematological and gastrointestinal toxicities are common in patients treated with cyclophosphamide and doxorubicin(3).
Extremely high proliferative capacity of hematopoietic system makes it the collateral target for chemotherapeutic agents. Chemotherapy-induced neutropenia are , because of the high susceptibility of neutrophil lineage to cytotoxic effects of cancer treatment. The drug-induced destruction of neutrophil precursors in bone marrow is the main cause of those symptoms. Decrease in neutrophil count is managed by the dose reduction and delays that decrease the dose intensity, where is maintaining the dose is important for favorable response to treatment(3). Another frequent and serious myelotoxic symptom in breast cancer chemotherapy is anemia. This condition may emerge from the disease itself, but the effect of concomitant administration of cytotoxic drugs is also the cause of drop in the hemoglobin level. Anemia has deleterious effect on patients' quality of life as well as on the treatment response. The suspected causes include blood loss, reduced or impaired erythrocytes production and high rate of red blood cells destruction or their reduced survival(4).
Chemotherapy-induced nausea and vomiting (CINV) is a common severe side effect for cancer patients undergoing emetic chemotherapy. The complete pathophysiology of CINV is not known but gastrointestinal (GI) side effects associated with anticancer chemotherapy are traditionally thought to be attributable to mucosal damage.
Nausea is complex in nature and probably depending on more than one etiological factor . Different pathways have been identified for acute and delayed CINV Also, nausea and vomiting can result in anorexia, decreased performance status, metabolic imbalance, wound dehiscence, esophageal tears and nutritional deficiency(5).
In the study we will focuse on the analysis of the relations between the polymorphic variants in some drug transporter genes with known or potential role in the AC-induced toxicity. Single nucleotide polymorphisms will analyzed in genes encoding proteins Involved in AC drug transport
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 20 to 75 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- all breast cancer females reciving (Ac regimen) at El-hosien University Hospital
Key inclusion criteria (3 listed)
- women who has confirmed diagnosis of breast cancer.
- patient who will be treated with cyclophosphamide and doxorubicin(AC) regimen only .
- patient take drug regimen for first time.
Key exclusion criteria (2 listed)
- 1. Patients with metastatic disease and with other previous tumors were excluded from this study 2. Pregnant or nursing female. 3. The patients who were diagnosed with cardiovascular disease or with low left ventricular ejection fraction.
- 4 .patients who had benign breast cancers, or had no clinical pathological information
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 polymorphismDNA 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
.1-The frequency of the genetic polymorphisms of ABCB1 in breast cancer patien
Time frame: up to 24 week
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 SLC22A16 in breast cancer patients
Time frame: up to 24 week
the blood samples will be DNA extracted by DNA extraction kit then single nucleotide polymorphisms of SL22A16 gene will be detected by real time PCR
2 secondary outcomes
Correlation between genetic polymorphisms of ABCB1 and toxicities from Doxorubicin-Cyclophosphamide regimen therapy
Time frame: up to 24 week
Correlation between genetic polymorphisms of SLC22A16 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 4 Dec 2020.
- 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 28747156Ludovini V, Antognelli C, Rulli A, Foglietta J, Pistola L, Eliana R, Floriani I, Nocentini G, Tofanetti FR, Piattoni S, Minenza E, Talesa VN, Sidoni A, Tonato M, Crino L, Gori S. Influence of chemotherapeutic drug-related gene polymorphisms on toxicity and survival of early breast cancer patients receiving adjuvant chemotherapy. BMC Cancer. 2017 Jul 26;17(1):502. doi: 10.1186/s12885-017-3483-2.
- Background3-U.S. department of health and human services(2017): Common Terminology Criteria for Adverse Events (CTCAE),National Cancer Institute ,2017,pp(4-6 ) ,pp(24-44).
- Background: PubMed 25677905Islam MS, Islam MS, Parvin S, Ahmed MU, Bin Sayeed MS, Uddin MM, Hussain SM, Hasnat A. Effect of GSTP1 and ABCC4 gene polymorphisms on response and toxicity of cyclophosphamide-epirubicin-5-fluorouracil-based chemotherapy in Bangladeshi breast cancer patients. Tumour Biol. 2015 Jul;36(7):5451-7. doi: 10.1007/s13277-015-3211-y. Epub 2015 Feb 13.
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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 for Girls
Wael helmy, Ass.prof principal investigator
Faculty of medicine Al-Azhar University for Boys
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 2 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 4 Dec 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 (002010000007613, hsalem@ut.edu.sa), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
.1-The frequency of the genetic polymorphisms of ABCB1 in breast cancer patien (time frame: up to 24 week). 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 NCT04654195, which also lists 4 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 4 Dec 2020.