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

Primary Purpose

Breast Cancer

Status

Active

Phase

Phase 1

Locations

Singapore

Study Type

Interventional

Intervention

Tamoxifen

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

National Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Dose-determination

Dose-confirmation

Arm Description

Outcomes

Primary Outcome Measures

Endoxifen blood concentration

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

Secondary Outcome Measures

Full Information

NCT ID

NCT04961632

First Posted

July 5, 2021

Last Updated

November 15, 2022

Sponsor

National Cancer Centre, Singapore

Collaborators

National Medical Research Council (NMRC), Singapore

1. Study Identification

Unique Protocol Identification Number

NCT04961632

Brief Title

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

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

December 23, 2020 (Actual)

Primary Completion Date

November 2025 (Anticipated)

Study Completion Date

November 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Cancer Centre, Singapore

Collaborators

National Medical Research Council (NMRC), Singapore

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Breast Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

75 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Dose-determination

Arm Type

Experimental

Arm Title

Dose-confirmation

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Tamoxifen

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Tamoxifen

Intervention Description

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

Primary Outcome Measure Information:

Title

Endoxifen blood concentration

Description

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

Time Frame

8 weeks after each tamoxifen dose level at 20mg, 30mg and 40mg

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Elaine Lim

Organizational Affiliation

National Cancer Centre, Singapore

Official's Role

Principal Investigator

Facility Information:

Facility Name

National Cancer Centre

City

Singapore

ZIP/Postal Code

169610

Country

Singapore

12. IPD Sharing Statement

Learn more about this trial

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

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