CYP2D6 Genotypes and Breast Cancer Clinical Outcomes in the Indonesian Population

Breast Cancer Clinical Trial

Official title:

CYP2D6 Genotypes and Breast Cancer Clinical Outcomes in the Indonesian Population (Pengaruh Genotipe CYP2D6 Terhadap Efektivitas Penggunaan Tamoksifen Untuk Pasien Kanker Payudara ER+ Pada Populasi Indonesia)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05501158
• Other study ID #: ID-TMS-02-20201012
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 1, 2021
• Est. completion date: June 30, 2024

Study information

• Verified date: August 2022
• Source: Nalagenetics Pte Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The utilization of tamoxifen is considerably high in Indonesia, with about 170,000 tamoxifen prescriptions filed in 2015. It is metabolized by the enzyme CYP2D6, resulting in its active metabolite, endoxifen, which has been proven to be effective in the prevention and treatment of breast cancer.

Studies showed the CYP2D6 gene has more than 100 variants; some of which are linked with reduced drug activity, while others do not have any pathological implications. The metabolizer profile of these variants is generally grouped into Ultra-rapid, Normal, Intermediate, and Poor Metabolizers (UM, NM, IM, and PM, respectively). In our previous study (NCT04312347), the investigators recruited 150 breast cancer patients who were taking adjusted dose of tamoxifen daily based on their CYP2D6 phenotype. Although the investigators have measured the endoxifen level of the patients with adjusted treatment, the clinical outcomes of the study are not yet conclusive.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: June 30, 2024
• Est. primary completion date: April 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. female

2. diagnosed with ER+ breast cancer

3. have been genotyped and classified as PM and IM in the previous study

4. are recommended by doctor to take tamoxifen 40 mg according to their metabolizer profile

5. have finished the definitive therapy course (surgery, chemotherapy, or radiotherapy).

Exclusion Criteria:

1. have other primary cancer aside from breast cancer.

2. those with residual tumor cells/have experienced second primary breast tumor.

3. patients who are recommended by doctor to switch to aromatase inhibitors (AI)

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Tamoxifen
Suggesting an increase in the dose of tamoxifen to those who have suboptimum level of endoxifen due to their genetic variations

Locations

Country	Name	City	State
Indonesia	MRCCC Siloam Hospitals Semanggi	Jakarta	DKI Jakarta

Sponsors (4)

Lead Sponsor	Collaborator
Nalagenetics Pte Ltd	Indonesia University, MRCCC Siloam Hospitals Semanggi, SJH Initiatives

Country where clinical trial is conducted

Indonesia, 

References & Publications (3)

Braal CL, Jager A, Hoop EO, Westenberg JD, Lommen KMWT, de Bruijn P, Vastbinder MB, van Rossum-Schornagel QC, Thijs-Visser MF, van Alphen RJ, Struik LEM, Zuetenhorst HJM, Mathijssen RHJ, Koolen SLW. Therapeutic Drug Monitoring of Endoxifen for Tamoxifen Precision Dosing: Feasible in Patients with Hormone-Sensitive Breast Cancer. Clin Pharmacokinet. 2022 Apr;61(4):527-537. doi: 10.1007/s40262-021-01077-z. Epub 2021 Nov 17. — View Citation

Lu J, Li H, Guo P, Shen R, Luo Y, Ge Q, Shi W, Li Y, Zhu W. The effect of CYP2D6 *10 polymorphism on adjuvant tamoxifen in Asian breast cancer patients: a meta-analysis. Onco Targets Ther. 2017 Nov 13;10:5429-5437. doi: 10.2147/OTT.S149197. eCollection 2017. — View Citation

Sanchez-Spitman A, Dezentjé V, Swen J, Moes DJAR, Böhringer S, Batman E, van Druten E, Smorenburg C, van Bochove A, Zeillemaker A, Jongen L, Los M, Neven P, Gelderblom H, Guchelaar HJ. Tamoxifen Pharmacogenetics and Metabolism: Results From the Prospective CYPTAM Study. J Clin Oncol. 2019 Mar 10;37(8):636-646. doi: 10.1200/JCO.18.00307. Epub 2019 Jan 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Long-term side effects of tamoxifen	Long-term side effects of tamoxifen, including heartburn, thromboembolic event, endometrial hyperplasia and uterine cancer, will also be monitored and documented using the Adverse Drug Reaction (ADR) reporting form provided by the Indonesian National Agency of Drug and Food Control.	3 year
Primary	Overall Survival rate	The percentage of study participants who are still alive by the end of this study after being diagnosed with breast cancer	3 year
Primary	Progression Survival rate	The percentage of study participants who live with the disease but the disease does not get worse by the end of this study	3 year