Therapeutic Dose Monitoring (TDM) of Tamoxifen

Phase 2

• Conditions: Breast Carcinoma; Cancer of Breast; Malignant Neoplasm of Breast; Breast Tumors; Breast Cancer
• Interventions: Drug: Tamoxifen 20 mg

• Registration Number: NCT05133674
• Lead Sponsor: Karolinska University Hospital

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.

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:

1. Female patients aged ≥ 18 years with hormone-positive stage 0-3 breast cancer.

2. Performance status Eastern Cooperative Oncology Group (ECOG) 0-2.

3. Ongoing daily adjuvant tamoxifen minimum of 2 months ± gonadotropin-releasing hormone (GnRH) analogues ± radiation therapy (RT) for stage 3 breast cancer.

4. Locally recurrent disease, previously treated with adjuvant tamoxifen.

5. Able to use software applications developed specifically for small, wireless computing devices, such as smartphones and tablets.

6. Have small, wireless computing devices, such as smartphones and tablets.

Exclusion Criteria:

1. Fulfilling any of the contraindications for tamoxifen.

2. Metastatic (stage IV) breast cancer.

3. Included in other clinical studies receiving not approved investigational medicinal drug.

4. Ongoing pregnancy or lactation.

5. 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 Timeline

• Study First Submitted: 2021-10-07
• Study First Submitted QC: 2021-11-15
• Study First Posted: 2021-11-24
• Study Start: 2022-04-04
• Status Verified: 2022-05
• Last Update Submitted: 2022-05-24
• Last Update Posted: 2022-05-25
• Primary Completion: 2022-12-31
• Study Completion: 2023-03-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 40

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
0	Tamoxifen 20 mg	Blood concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen will be measured.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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).
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 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.
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.

Trial Locations

Locations (1)

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden