Dose-determining and Dose-confirmatory Study to Investigate the Optimal Dose of Tamoxifen in Breast Cancer Patients According to Genotype Status of TCF20 rs932376

National Cancer Centre, Singapore (Other)
Overall Status
Recruiting ID
National Medical Research Council (NMRC), Singapore (Other)

Study Details

Study Description

Brief Summary

The investigators hypothesize that the TCF20 rs932376 locus controls endoxifen levels in estrogen receptor (ER)-positive breast cancer patients on tamoxifen therapy and that the requirement of tamoxifen dose to achieve therapeutic levels of endoxifen varies according to the genotype status of the patient's at the TCF20 rs932376 locus.

Patients will receive escalating doses of tamoxifen according to their TCF20 rs932376 genotype status. Patients on 20mg tamoxifen daily for 8 weeks or longer will provide blood samples for analysis of tamoxifen and its metabolites. Patients assess with >30nM endoxifen concentrations will continue with 20mg tamoxifen dose. Patients who have endoxifen concentrations <30nM will receive dose increments of 10mg every 8 weeks until they achieve endoxifen threshold of >30nM or reach maximum dose level of 40mg/day.

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Anticipated Enrollment :
75 participants
Intervention Model:
Sequential Assignment
None (Open Label)
Primary Purpose:
Official Title:
An Open-label, Single-institution, Dose-determining (Part 1) and Dose-confirmatory (Part II) Study to Investigate the Optimal Dose of Tamoxifen in Breast Cancer Patients Harboring Different TCF20 rs932376 Variant Alleles
Actual Study Start Date :
Dec 23, 2020
Anticipated Primary Completion Date :
Nov 1, 2025
Anticipated Study Completion Date :
Nov 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Dose-determination

Drug: Tamoxifen
Patients taking 20mg tamoxifen will receive dose increments of 10mg every 8 weeks until endoxin threshold of >30nM or the maximum dose of 40mg/day is reached. The escalated dose will be taken for 1 year before reverting back to 20mg.

Experimental: Dose-confirmation

Drug: Tamoxifen
Patients will take tamoxifen at the ascribed genotype-determined dose as determined in the dose-determination phase.

Outcome Measures

Primary Outcome Measures

  1. Endoxifen blood concentration [8 weeks after each tamoxifen dose level at 20mg, 30mg and 40mg]

    To determine the optimal dose of tamoxifen required to achieve therapeutic endoxifen levels for each TCF20 rs932376 genotype group in the dose-determination phase

Eligibility Criteria


Ages Eligible for Study:
21 Years and Older
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Inclusion Criteria:
  • Histologically or cytologically confirmed stage I to IV breast cancer

  • Age greater than 21 years

  • Estrogen- or progesterone-receptor positive tumours

  • Patients receiving tamoxifen 20mg daily as monotherapy

  • Patients currently taking tamoxifen in either adjuvant or metastatic setting for greater than or equal to 8 weeks (for Dose determination and confirmation phases)

  • Patients who will commence on tamoxifen therapy in either adjuvant or metastatic setting (for Dose confirmation phase only)

  • Written and informed consent from participating patients

Exclusion Criteria:
  • Patients with expected survival less than 6 months

  • Patients who are human epidermal growth factor receptor 2 (HER2)-postitive

  • Inability to provide informed consent

  • Patients receiving CYP2D6 inhibitors or inducers within the past four weeks from the time of study enrollment. However, patients started in CYP2D6 inhibitors or inducers after commencing on tamoxifen therapy will not be excluded from the study.

  • Pregnancy

  • Patients with prior malignancies other than those who have received curative treatment for basal cell carcinoma of the skin or carcinoma in situ of the uterine cervix

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/ social situations that would limit compliance with study requirements.

  • Patients who have documented prior allergic reaction to tamoxifen

Contacts and Locations


Site City State Country Postal Code
1 National Cancer Centre Singapore Singapore 169610

Sponsors and Collaborators

  • National Cancer Centre, Singapore
  • National Medical Research Council (NMRC), Singapore


  • Principal Investigator: Elaine Lim, National Cancer Centre, Singapore

Study Documents (Full-Text)

None provided.

More Information


None provided.
Responsible Party:
National Cancer Centre, Singapore Identifier:
Other Study ID Numbers:
  • TCF20-BRE-01
First Posted:
Jul 14, 2021
Last Update Posted:
Jul 14, 2021
Last Verified:
Jul 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Studies a U.S. FDA-regulated Device Product:
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jul 14, 2021