Therapeutic Dose Monitoring (TDM) of Tamoxifen

Sponsor

Karolinska University Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05133674

Collaborator

(none)

Enrollment

Location

Arm

10.9

Anticipated Duration (Months)

3.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Tamoxifen is a potent and effective drug reducing the risk of dying from breast cancer in the adjuvant setting. Although more modern drugs have partly replaced tamoxifen, it is helpful in the neoadjuvant and metastatic settings as a single drug. Despite that, in the adjuvant setting, it is a valuable drug.

This study aims to validate and study the feasibility of serial assessments, including therapeutic drug monitoring of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen by capillary blood sampling, combined with patient-reported symptom scores. This will provide preliminary data to allow us to develop a future multicentre randomised clinical trial of personalised dose monitoring and adjustment of adjuvant tamoxifen therapy to enhance the quality of life and breast cancer outcomes.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Breast Carcinoma Breast Tumors Cancer of Breast Malignant Neoplasm of Breast	Drug: Tamoxifen 20 mg	Phase 2

Detailed Description

This repeated-measures, prospective, open-label, single-centre study is designed for women with stage 0-3 breast cancer receiving adjuvant tamoxifen 20 mg/day.

Inclusion criteria:

Female patients aged ≥ 18 years with hormone-positive stage 0-3 breast cancer.
Performance status Eastern Cooperative Oncology Group (ECOG) 0-2.
Ongoing daily adjuvant tamoxifen minimum of 2 months ± gonadotropin-releasing hormone (GnRH) analogues ± radiation therapy (RT) for stage 3 breast cancer.
Locally recurrent disease, previously treated with adjuvant tamoxifen.
Able to use software applications developed specifically for small, wireless computing devices, such as smartphones and tablets.
Have small, wireless computing devices, such as smartphones and tablets.

Exclusion Criteria:

Fulfilling any of the contraindications for tamoxifen.
Metastatic (stage IV) breast cancer.
Included in other clinical studies receiving not approved investigational medicinal drug.
Ongoing pregnancy or lactation.
Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

No. Of Subjects: 40 female subjects.

Measured components: Tamoxifen, 4-hydroxytamoxifen and Z-endoxifen

Study design: Blood samples for measurement of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen will be drawn capillary in total at 4-time points, at inclusion (baseline), and after 1, 2, and 3 weeks for each participant; and venously in total at 2-time points, at inclusion (baseline), and after 3 weeks for each participant.

At each time, participants will be asked to leave 2 vials of capillary blood (50ul x2) using the rhelise™ kit and 2 samples of conventional venous blood for blood and plasma (5 ml x 2).

Study Design

Study Type:

Interventional

Actual Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Therapeutic Dose Monitoring (TDM) of Tamoxifen and Its Active Metabolites in Combination With Patient-reported Symptom Scores Among Patients With Breast Cancer Receiving Adjuvant Tamoxifen Treatment

Actual Study Start Date :

Apr 4, 2022

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 0 Blood concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen will be measured.	Drug: Tamoxifen 20 mg i) a self-testing capillary kit, the rhelise™ kit for measuring the concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen and ii) a patient interactive digital tool (app) mBraze to collect data about symptoms and guide breast cancer patients on adjuvant tamoxifen.

Arm

Intervention/Treatment

Experimental: 0

Blood concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen will be measured.

Drug: Tamoxifen 20 mg

i) a self-testing capillary kit, the rhelise™ kit for measuring the concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen and ii) a patient interactive digital tool (app) mBraze to collect data about symptoms and guide breast cancer patients on adjuvant tamoxifen.

Outcome Measures

Primary Outcome Measures

To validate the rhelise™ kit for monitoring tamoxifen, 4-hydroxytamoxifen and Z-endoxifen among patients recommended or who have ongoing adjuvant tamoxifen. [At at inclusion (baseline) for each participant.]
Blood concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen at baseline, two weeks, 1, 2, and 3 weeks by capillary and venous blood sampling (whole blood/plasma).
To validate the rhelise™ kit for monitoring tamoxifen, 4-hydroxytamoxifen and Z-endoxifen among patients recommended or who have ongoing adjuvant tamoxifen. [At week 3 after inclusion for each participant.]
Blood concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen at baseline, two weeks, 1, 2, and 3 weeks by capillary and venous blood sampling (whole blood/plasma).

Secondary Outcome Measures

To test the correlations of concentrations found in the capillary sample (rhelise™ kit) and the venous blood sample (gold standard). [At 4-time points, at inclusion (baseline), and after 1, 2, and 3 weeks for each participant.]
Correlations of blood concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen between venous blood samples and capillary blood samples (Sensitivity and specificity).
To validate user acceptability and feasibility of self-testing the capillary kit. [At 4-time points, at inclusion (baseline), and after 1, 2, and 3 weeks for each participant.]
Capillary blood test concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen were taken by the patient and the research nurse.
Symptom distresses scores measured by the patient interactive digital tool (application) mBraze. [at baseline and 3 weeks.]
To compare and correlate blood concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen with patient-reported outcome measures and the application mBraze for symptom self-monitoring. [at baseline and 3 weeks]
Correlations between tamoxifen, 4-hydroxytamoxifen and Z-endoxifen concentrations and symptom distress score ((fatigue, insomnia, pain, body image, and systemic therapy side-effect and cognitive-, emotional-, role-, sexual and social functioning). Correlations between tamoxifen, 4-hydroxytamoxifen and Z-endoxifen concentrations and symptom distress in the same patient.
To validate the user experience of the mBraze app. [at 3 weeks.]
- The interview on user acceptability and attitudes toward mBraze.
To validate the usability of the mBraze app. [at 3 weeks.]
- Self-reported usability and user experience of the mBraze app measured with system usability scale (SUS).
To determine user acceptability and attitudes toward self-testing. [at 3 weeks.]
- The interview on user acceptability and attitudes toward self-testing.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Female patients aged ≥ 18 years with hormone-positive stage 0-3 breast cancer.
Performance status ECOG 0-2.
Ongoing daily adjuvant tamoxifen minimum of 2 months ± GnRH analogues ± RT for stage 3 breast cancer.
Locally recurrent disease, previously treated with adjuvant tamoxifen.
Able to use software applications developed specifically for small, wireless computing devices, such as smartphones and tablets.
Have small, wireless computing devices, such as smartphones and tablets.

Exclusion Criteria:

Fulfilling any of the contraindications for tamoxifen.
Metastatic (stage IV) breast cancer.
Included in other clinical studies receiving not approved investigational medicinal drug.
Ongoing pregnancy or lactation.
Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.