NCT03504631

Brief 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

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
117

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Oct 2017

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2017

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

April 12, 2018

Completed
8 days until next milestone

First Posted

Study publicly available on registry

April 20, 2018

Completed
5 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2018

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

April 24, 2018

Status Verified

April 1, 2018

Enrollment Period

1 year

First QC Date

April 12, 2018

Last Update Submit

April 23, 2018

Conditions

Breast Cancer Female

Keywords

tamoxifenbreast cancerZ-endoxifen

Outcome Measures

Primary Outcomes (1)

  • Genotype and phenotype of CYP2D6

    Number of subjects with CYP2D6 genotype and phenotype who had steady state level

    4 months

Secondary Outcomes (1)

  • Z-endoxifen

    4 months

Study Arms (1)

Breast cancer patients on tamoxifen

Patients currently on treatment with tamoxifen for at least 4 months.

Other: No intervention

Interventions

No interventionOTHER

no intervention

Breast cancer patients on tamoxifen

Eligibility Criteria

Sexfemale(Gender-based eligibility)
Gender Eligibility DetailsFemale only
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Outpatient breast cancer patients on tamoxifen treatment for at least 4 months

You may qualify if:

  • Breast cancer patients on tamoxifen treatment for at least 4 months

You may not qualify if:

  • Abnormalities in liver markers (AST \>2.5 x ULN)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dharmais hospital

Jakarta, DKI Jakarta, 11420, Indonesia

RECRUITING

Related Publications (11)

  • 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.

    PMID: 21430657BACKGROUND

  • Jager 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.

    PMID: 24390246BACKGROUND

  • Tamminga 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.

    PMID: 11417446BACKGROUND

  • Desta 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.

    PMID: 15159443BACKGROUND

  • Fotoohi 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.

    PMID: 26485084BACKGROUND

  • Hennig 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.

    PMID: 26232141BACKGROUND

  • Antunes 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.

    PMID: 22777153BACKGROUND

  • Lei 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.

    PMID: 27648149BACKGROUND

  • Hawse 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.

    PMID: 23382923BACKGROUND

  • Bagheri 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.

    PMID: 25999696BACKGROUND

  • Zhou 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.

    PMID: 19817501BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples from breast cancer patients treated with Z-endoxifen were drawn for analysis of genotype and phenotype of CYP2D6, as well as the plasma concentration of Z-endoxifen

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Study Officials

  • Rianto Setiabudy, MD, PhD

    Indonesia University

    STUDY DIRECTOR

Central Study Contacts

Yenny, MD

CONTACT

+628159661333yenfarmako@gmail.com

Study Design

Study Type
observational
Observational Model
CASE ONLY
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Head of Pharmacology

Study Record Dates

First Submitted

April 12, 2018

First Posted

April 20, 2018

Study Start

October 1, 2017

Primary Completion

October 1, 2018

Study Completion

December 1, 2018

Last Updated

April 24, 2018

Record last verified: 2018-04

Data Sharing

IPD Sharing
Will not share

Locations

ID(1)