Genotyping and Phenotyping of CYP2D6 Breast Cancer Patients on Tamoxifen

Breast Cancer Female Clinical Trial

Official title:

Genotyping and Phenotyping of CYP2D6 as Predictor of Z-endoxifen Plasma Levels in Breast Cancer Patients on Tamoxifen Treatment

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03504631
• Other study ID #: 1001
• Status: Recruiting
• First received: April 12, 2018
• Last updated: April 23, 2018
• Start date: October 1, 2017
• Est. completion date: December 1, 2018

Study information

• Verified date: April 2018
• Source: Trisakti University
• Contact: Yenny, MD
• Phone: +628159661333
• Email: yenfarmako[@]gmail.com
• Is FDA regulated: No
• Study type: Observational

Clinical 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 117
• Est. completion date: December 1, 2018
• Est. primary completion date: October 1, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Breast Cancer Female
• Breast Neoplasms

Intervention

Other:
• No intervention
no intervention

Locations

Country	Name	City	State
Indonesia	Dharmais hospital	Jakarta	DKI Jakarta

Sponsors (2)

Lead Sponsor	Collaborator
Trisakti University	Dharmais National Cancer Center Hospital

Country where clinical trial is conducted

Indonesia, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. Epub 2004 May 24. — View Citation

Fotoohi AK, Karim H, Lafolie P, Pohanka A, Östervall 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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genotype and phenotype of CYP2D6	Number of subjects with CYP2D6 genotype and phenotype who had steady state level	4 months
Secondary	Z-endoxifen	Number of subjects with plasma levels of Z-endoxifen more than 5.9 ng/mL	4 months