Clinical trial NCT05501158: CYP2D6 Genotypes and Breast Cancer Clinical Outcomes in the Indonesian Population
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Breast Cancer
Lead sponsor: Nalagenetics Pte Ltd
Sponsor class: INDUSTRY
Collaborators: name: SJH Initiatives
name: Indonesia University
name: MRCCC Siloam Hospitals Semanggi
First posted: 2022-08-15
Enrollment: 150
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: This is a prospective cohort study involving the breast cancer patients who participated in our previous study. Patients who are recommended to adjust their tamoxifen dosage to 40 mg and remain on tamoxifen 20 mg will be all followed up for 3 years to evaluate the clinical outcomes and medication side effects
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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)

Primary outcomes:
measure: Overall Survival rate
timeFrame: 3 year
measure: Progression Survival rate
timeFrame: 3 year
Secondary outcomes:
Other outcomes:
measure: Long-term side effects of tamoxifen
timeFrame: 3 year
Locations:
city: Jakarta
country: Indonesia
facility: MRCCC Siloam Hospitals Semanggi
state: DKI Jakarta
Study officials:
affiliation: Fakultas Farmasi Universitas Indonesia
name: Baitha Maggadani, MPharm
role: STUDY_CHAIR
affiliation: MRCCC Siloam Hospitals Semanggi
name: Arief Winata, MD
role: STUDY_CHAIR
affiliation: SJH Innitiatives
name: Samuel Haryono, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Nalagenetics Pte Ltd
name: Fatma Aldila, PharmD
role: STUDY_CHAIR
References:
citation: 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.
citation: Sanchez-Spitman A, Dezentje V, Swen J, Moes DJAR, Bohringer 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.
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.