Breast Cancer FemaleNCT03504631
Genotyping and Phenotyping of CYP2D6 Breast Cancer Patients on Tamoxifen
An observational study of Breast Cancer Female, run by Trisakti University at 1 site in Indonesia.
Trial summary
This study is an observational study to determine phenotype and genotype of CYP2D6 as predictors of z-endoxifen concentrations in plasma of outgoing patients treated with tamoxifen for at least 4 months Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Breast Cancer Female
- How many people
- 117 participants
- Where
- 1 siteIndonesia
- Study dates
- 1 Oct 2017to 1 Dec 2018
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Study population: Outpatient breast cancer patients on tamoxifen treatment for at least 4 months
Who may be able to join
- Breast cancer patients on tamoxifen treatment for at least 4 months
Who cannot join
- Abnormalities in liver markers (AST >2.5 x ULN)
Trial locations and contacts
1 site in 1 country.
Indonesia1 site, 1 recruiting
- Recruiting
Dharmais hospital
Jakarta, DKI Jakarta, 11420
Denni Jokopurwanto, MD, PhD, +62811153590, dennijoko@gmail.com
About this study
Official title: Genotyping and Phenotyping of CYP2D6 as Predictor of Z-endoxifen Plasma Levels in Breast Cancer Patients on Tamoxifen Treatment
This study is an observational study to determine phenotype and genotype of CYP2D6 as predictors of z-endoxifen concentrations in plasma of outgoing patients treated with tamoxifen for at least 4 months
Read the detailed description
Tamoxifen is an antiestrogen drug with concentration dependent properties, with z-endoxifen known as active metabolite. Until know therapeutic range for z-endoxifen to improve treatment response was not known. Variation response on tamoxifen can be cause of genetic polymorphism CYP2D6 that can be different between interindividul and ethnic.
The aim of this study is to determine phenotype and genotype of CYP2D6 as predictors of z-endoxifen concentrations in plasma of outgoing patients treated with tamoxifen for at least 4 months
- Conditions
- Breast Cancer Female
- Being tested
- No intervention
- Keywords
- tamoxifen, breast cancer, Z-endoxifen
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No interventionOther
no intervention
| Study group | Role | What they receive |
|---|---|---|
| Breast cancer patients on tamoxifen | Patients currently on treatment with tamoxifen for at least 4 months. Receives: Other: No intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Genotype and phenotype of CYP2D6
Number of subjects with CYP2D6 genotype and phenotype who had steady state level
Measured: 4 months
Secondary outcomes (1)
Z-endoxifen
Number of subjects with plasma levels of Z-endoxifen more than 5.9 ng/mL
Measured: 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2018
- Study start1 Oct 2017
- Primary completion1 Oct 2018 (estimated)
- Study completion1 Dec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Breast Cancer FemaleStudies 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
- Case only
- Time perspective
- Cross-sectional
- Enrolment
- 117 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Trisakti University
- Sponsor type
- University, hospital or other
- Collaborators
- Dharmais National Cancer Center Hospital
- Responsible party
- Principal investigator, Yenny Farmako, Trisakti University
- Investigators
- Rianto Setiabudy, MD, PhD, Study director, Universitas Indonesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03504631
- Sponsor's protocol ID
- 1001
- Status last verified
- Apr 2018
- First submitted
- 12 Apr 2018
- Last updated
- 24 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Madlensky L, Natarajan L, Tchu S, Pu M, Mortimer J, Flatt SW, Nikoloff DM, Hillman G, Fontecha MR, Lawrence HJ, Parker BA, Wu AH, Pierce JP. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther. 2011 May;89(5):718-25. doi: 10.1038/clpt.2011.32. Epub 2011 Mar 23.
PubMed 21430657Jager NG, Rosing H, Schellens JH, Linn SC, Beijnen JH. Tamoxifen dose and serum concentrations of tamoxifen and six of its metabolites in routine clinical outpatient care. Breast Cancer Res Treat. 2014 Feb;143(3):477-83. doi: 10.1007/s10549-013-2826-1. Epub 2014 Jan 5.
PubMed 24390246Tamminga WJ, Wemer J, Oosterhuis B, Brakenhoff JP, Gerrits MG, de Zeeuw RA, de Leij LF, Jonkman JH. An optimized methodology for combined phenotyping and genotyping on CYP2D6 and CYP2C19. Eur J Clin Pharmacol. 2001 May;57(2):143-6. doi: 10.1007/s002280100273.
PubMed 11417446Desta Z, Ward BA, Soukhova NV, Flockhart DA. Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75. doi: 10.1124/jpet.104.065607. Epub 2004 May 24.
PubMed 15159443Fotoohi AK, Karim H, Lafolie P, Pohanka A, Ostervall J, Hatschek T, Vitols S. Pronounced Interindividual But Not Intraindividual Variation in Tamoxifen and Metabolite Levels in Plasma During Adjuvant Treatment of Women With Early Breast Cancer. Ther Drug Monit. 2016 Apr;38(2):239-45. doi: 10.1097/FTD.0000000000000257.
PubMed 26485084Hennig EE, Piatkowska M, Karczmarski J, Goryca K, Brewczynska E, Jazwiec R, Kluska A, Omiotek R, Paziewska A, Dadlez M, Ostrowski J. Limited predictive value of achieving beneficial plasma (Z)-endoxifen threshold level by CYP2D6 genotyping in tamoxifen-treated Polish women with breast cancer. BMC Cancer. 2015 Aug 1;15:570. doi: 10.1186/s12885-015-1575-4.
PubMed 26232141Antunes MV, Linden R, Santos TV, Wallemacq P, Haufroid V, Classen JF, Andreolla H, Costa N, Fontanive TO, Rosa DD. Endoxifen levels and its association with CYP2D6 genotype and phenotype: evaluation of a southern Brazilian population under tamoxifen pharmacotherapy. Ther Drug Monit. 2012 Aug;34(4):422-31. doi: 10.1097/FTD.0b013e318260b46e.
PubMed 22777153Lei L, Wang X, Wu XD, Wang Z, Chen ZH, Zheng YB, Wang XJ. Association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome of breast cancer after tamoxifen adjuvant endocrine therapy in Chinese population. Am J Transl Res. 2016 Aug 15;8(8):3585-92. eCollection 2016.
PubMed 27648149Hawse JR, Subramaniam M, Cicek M, Wu X, Gingery A, Grygo SB, Sun Z, Pitel KS, Lingle WL, Goetz MP, Ingle JN, Spelsberg TC. Endoxifen's molecular mechanisms of action are concentration dependent and different than that of other anti-estrogens. PLoS One. 2013;8(1):e54613. doi: 10.1371/journal.pone.0054613. Epub 2013 Jan 28.
PubMed 23382923Bagheri A, Kamalidehghan B, Haghshenas M, Azadfar P, Akbari L, Sangtarash MH, Vejdandoust F, Ahmadipour F, Meng GY, Houshmand M. Prevalence of the CYP2D6*10 (C100T), *4 (G1846A), and *14 (G1758A) alleles among Iranians of different ethnicities. Drug Des Devel Ther. 2015 May 13;9:2627-34. doi: 10.2147/DDDT.S79709. eCollection 2015.
PubMed 25999696Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009;48(11):689-723. doi: 10.2165/11318030-000000000-00000.
PubMed 19817501
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genotyping and Phenotyping of CYP2D6 as Predictor of Z-endoxifen Plasma Levels in Breast Cancer Patients on Tamoxifen Treatment
- ClinicalTrials.gov ID
- NCT03504631
- Acronym / sponsor ID
- 1001
- Conditions
- Breast Cancer Female
- Keywords
- tamoxifen, breast cancer, Z-endoxifen
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 117 participants (estimated)
- Lead sponsor
- Trisakti UniversityUniversity, hospital or other
- Collaborators
- Dharmais National Cancer Center Hospital
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 1 Oct 2018 (estimated)
- Study completion
- 1 Dec 2018 (estimated)
- First posted
- 20 Apr 2018 (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.
This study is an observational study to determine phenotype and genotype of CYP2D6 as predictors of z-endoxifen concentrations in plasma of outgoing patients treated with tamoxifen for at least 4 months
Detailed description
Tamoxifen is an antiestrogen drug with concentration dependent properties, with z-endoxifen known as active metabolite. Until know therapeutic range for z-endoxifen to improve treatment response was not known. Variation response on tamoxifen can be cause of genetic polymorphism CYP2D6 that can be different between interindividul and ethnic.
The aim of this study is to determine phenotype and genotype of CYP2D6 as predictors of z-endoxifen concentrations in plasma of outgoing patients treated with tamoxifen for at least 4 months
Study design
- Observational model
- Case only
- Time perspective
- Cross-sectional
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Breast cancer patients on tamoxifen | – | Other: No interventionPatients currently on treatment with tamoxifen for at least 4 months. |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Outpatient breast cancer patients on tamoxifen treatment for at least 4 months
Key inclusion criteria (1 listed)
- Breast cancer patients on tamoxifen treatment for at least 4 months
Key exclusion criteria (1 listed)
- Abnormalities in liver markers (AST >2.5 x ULN)
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 |
|---|---|---|
| No interventionno intervention | Other | Breast cancer patients on tamoxifen |
Primary outcome
Genotype and phenotype of CYP2D6
Time frame: 4 months
Number of subjects with CYP2D6 genotype and phenotype who had steady state level
1 secondary outcome
Z-endoxifen
Time frame: 4 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2018.
- Background: PubMed 21430657Madlensky L, Natarajan L, Tchu S, Pu M, Mortimer J, Flatt SW, Nikoloff DM, Hillman G, Fontecha MR, Lawrence HJ, Parker BA, Wu AH, Pierce JP. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther. 2011 May;89(5):718-25. doi: 10.1038/clpt.2011.32. Epub 2011 Mar 23.
- Background: PubMed 24390246Jager NG, Rosing H, Schellens JH, Linn SC, Beijnen JH. Tamoxifen dose and serum concentrations of tamoxifen and six of its metabolites in routine clinical outpatient care. Breast Cancer Res Treat. 2014 Feb;143(3):477-83. doi: 10.1007/s10549-013-2826-1. Epub 2014 Jan 5.
- Background: PubMed 11417446Tamminga WJ, Wemer J, Oosterhuis B, Brakenhoff JP, Gerrits MG, de Zeeuw RA, de Leij LF, Jonkman JH. An optimized methodology for combined phenotyping and genotyping on CYP2D6 and CYP2C19. Eur J Clin Pharmacol. 2001 May;57(2):143-6. doi: 10.1007/s002280100273.
- Background: PubMed 15159443Desta Z, Ward BA, Soukhova NV, Flockhart DA. Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004 Sep;310(3):1062-75. doi: 10.1124/jpet.104.065607. Epub 2004 May 24.
- Background: PubMed 26485084Fotoohi AK, Karim H, Lafolie P, Pohanka A, Ostervall J, Hatschek T, Vitols S. Pronounced Interindividual But Not Intraindividual Variation in Tamoxifen and Metabolite Levels in Plasma During Adjuvant Treatment of Women With Early Breast Cancer. Ther Drug Monit. 2016 Apr;38(2):239-45. doi: 10.1097/FTD.0000000000000257.
- Background: PubMed 26232141Hennig EE, Piatkowska M, Karczmarski J, Goryca K, Brewczynska E, Jazwiec R, Kluska A, Omiotek R, Paziewska A, Dadlez M, Ostrowski J. Limited predictive value of achieving beneficial plasma (Z)-endoxifen threshold level by CYP2D6 genotyping in tamoxifen-treated Polish women with breast cancer. BMC Cancer. 2015 Aug 1;15:570. doi: 10.1186/s12885-015-1575-4.
- Background: PubMed 22777153Antunes MV, Linden R, Santos TV, Wallemacq P, Haufroid V, Classen JF, Andreolla H, Costa N, Fontanive TO, Rosa DD. Endoxifen levels and its association with CYP2D6 genotype and phenotype: evaluation of a southern Brazilian population under tamoxifen pharmacotherapy. Ther Drug Monit. 2012 Aug;34(4):422-31. doi: 10.1097/FTD.0b013e318260b46e.
- Background: PubMed 27648149Lei L, Wang X, Wu XD, Wang Z, Chen ZH, Zheng YB, Wang XJ. Association of CYP2D6*10 (c.100C>T) polymorphisms with clinical outcome of breast cancer after tamoxifen adjuvant endocrine therapy in Chinese population. Am J Transl Res. 2016 Aug 15;8(8):3585-92. eCollection 2016.
- Background: PubMed 23382923Hawse JR, Subramaniam M, Cicek M, Wu X, Gingery A, Grygo SB, Sun Z, Pitel KS, Lingle WL, Goetz MP, Ingle JN, Spelsberg TC. Endoxifen's molecular mechanisms of action are concentration dependent and different than that of other anti-estrogens. PLoS One. 2013;8(1):e54613. doi: 10.1371/journal.pone.0054613. Epub 2013 Jan 28.
- Background: PubMed 25999696Bagheri A, Kamalidehghan B, Haghshenas M, Azadfar P, Akbari L, Sangtarash MH, Vejdandoust F, Ahmadipour F, Meng GY, Houshmand M. Prevalence of the CYP2D6*10 (C100T), *4 (G1846A), and *14 (G1758A) alleles among Iranians of different ethnicities. Drug Des Devel Ther. 2015 May 13;9:2627-34. doi: 10.2147/DDDT.S79709. eCollection 2015.
- Background: PubMed 19817501Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: Part I. Clin Pharmacokinet. 2009;48(11):689-723. doi: 10.2165/11318030-000000000-00000.
- Individual participant dataSharing planned: No
Related trials for Breast Cancer Female
Recruiting
Decision Support for Chemoprevention
Breast Cancer
Not yet recruiting
Geriatric Oncology Assessment and Coping Skills Training for Older Women on Aromatase Inhibitor Therapy
Breast Cancer, Hormone Receptor Positive, Aromatase Inhibitor-Associated Arthralgia
Recruiting
The Vanguard Study: Testing a New Way to Screen for Cancer
Bladder Carcinoma, Breast Carcinoma
Active, not recruitingPhase 1
A Phase 1 Study of XL309 (ISM3091) Alone and in Combination in Participants With Advanced Solid Tumors
Advanced Solid Tumor
RecruitingPhase 1
A Phase I Study of CG-7321 Monotherapy or Combination Therapy in Advanced Solid Tumors
Advanced Solid Tumors, Breast Cancer
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.
Rianto Setiabudy, MD, PhD study director
Universitas Indonesia
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 Female, run by Trisakti University at 1 site in Indonesia.
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 1 inclusion and 1 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 24 Apr 2018. 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 Indonesia. 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 Yenny, MD (+628159661333, yenfarmako@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Genotype and phenotype of CYP2D6 (time frame: 4 months). 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 NCT03504631, which also lists 11 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 24 Apr 2018.