CYP2D6 Genotypes and Breast Cancer Clinical Outcomes in the Indonesian Population
August 17, 2022 updated by: Nalagenetics Pte Ltd
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)
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.
Study Overview
Study Type
Interventional
Enrollment (Actual)
150
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
DKI Jakarta
-
Jakarta, DKI Jakarta, Indonesia, 12930
- MRCCC Siloam Hospitals Semanggi
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- ADULT
- OLDER_ADULT
- CHILD
Accepts Healthy Volunteers
No
Genders Eligible for Study
Female
Description
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NON_RANDOMIZED
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
EXPERIMENTAL: Dose adjustment of tamoxifen
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.
|
Suggesting an increase in the dose of tamoxifen to those who have suboptimum level of endoxifen due to their genetic variations
|
|
NO_INTERVENTION: Standard dose of tamoxifen
Those identified as Normal Metabolizers (NMs) from our previous study remain on tamoxifen 20 mg per day.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Overall Survival rate
Time Frame: 3 year
|
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
Time Frame: 3 year
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Long-term side effects of tamoxifen
Time Frame: 3 year
|
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
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Baitha Maggadani, MPharm, Fakultas Farmasi Universitas Indonesia
- Study Chair: Arief Winata, MD, MRCCC Siloam Hospitals Semanggi
- Principal Investigator: Samuel Haryono, MD, PhD, SJH Innitiatives
- Study Chair: Fatma Aldila, PharmD, Nalagenetics Pte Ltd
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ACTUAL)
January 1, 2021
Primary Completion (ANTICIPATED)
April 30, 2024
Study Completion (ANTICIPATED)
June 30, 2024
Study Registration Dates
First Submitted
August 12, 2022
First Submitted That Met QC Criteria
August 12, 2022
First Posted (ACTUAL)
August 15, 2022
Study Record Updates
Last Update Posted (ACTUAL)
August 19, 2022
Last Update Submitted That Met QC Criteria
August 17, 2022
Last Verified
August 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Hormone Antagonists
- Bone Density Conservation Agents
- Estrogen Antagonists
- Selective Estrogen Receptor Modulators
- Estrogen Receptor Modulators
- Tamoxifen
Other Study ID Numbers
- ID-TMS-02-20201012
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.