CYP2D6 Genotypes and Breast Cancer Clinical Outcomes in the Indonesian Population

NCT05501158 | Unknown

• 1 other identifier: ID-TMS-02-20201012
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Other Outcomes (1)

• Long-term side effects of tamoxifen

  3 year

Study Arms (2)

Dose adjustment of tamoxifen

EXPERIMENTAL

Following the CPIC guidelines, those identified as Poor Metabolizers (PMs) and Intermediate Metabolizers (IMs) from our previous study are recommended to adjust their tamoxifen dosage to 40 mg per day.

Drug: Tamoxifen

Standard dose of tamoxifen

NO INTERVENTION

Those identified as Normal Metabolizers (NMs) from our previous study remain on tamoxifen 20 mg per day.

Interventions

Tamoxifen DRUG

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

Dose adjustment of tamoxifen

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• female
• diagnosed with ER+ breast cancer
• have been genotyped and classified as PM and IM in the previous study
• are recommended by doctor to take tamoxifen 40 mg according to their metabolizer profile
• have finished the definitive therapy course (surgery, chemotherapy, or radiotherapy).

You may not qualify if:

• have other primary cancer aside from breast cancer.
• those with residual tumor cells/have experienced second primary breast tumor.
• patients who are recommended by doctor to switch to aromatase inhibitors (AI)

Sponsors & Collaborators

• Nalagenetics Pte Ltd: lead
• SJH Initiatives: collaborator
• Indonesia University: collaborator
• MRCCC Siloam Hospitals Semanggi: collaborator

Study Sites (1)

MRCCC Siloam Hospitals Semanggi

Jakarta, DKI Jakarta, 12930, Indonesia

Location

Related 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.

  PMID: 34786650 BACKGROUND

• 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.

  PMID: 30676859 BACKGROUND

• 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.

  PMID: 29180876 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Baitha Maggadani, MPharm

  Fakultas Farmasi Universitas Indonesia

  STUDY CHAIR

• Arief Winata, MD

  MRCCC Siloam Hospitals Semanggi

  STUDY CHAIR

• Samuel Haryono, MD, PhD

  SJH Innitiatives

  PRINCIPAL INVESTIGATOR

• Fatma Aldila, PharmD

  Nalagenetics Pte Ltd

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: August 12, 2022
• First Posted: August 15, 2022
• Study Start: January 1, 2021
• Primary Completion: April 30, 2024
• Study Completion: June 30, 2024
• Last Updated: August 19, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

ID (1)