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Breast Neoplasms

Breast Diseases

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Tamoxifen

Estrogens

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Afimoxifene

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

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

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.

Tamoxifen 20 mg

Elham Hedayati, MD PhD

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.

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).

Therapeutic Dose Monitoring (TDM) of Tamoxifen

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

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).

Correlations of blood concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen between venous blood samples and capillary blood samples (Sensitivity and specificity).

Capillary blood test concentrations of tamoxifen, 4-hydroxytamoxifen and Z-endoxifen were taken by the patient and the research nurse.

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.

- The interview on user acceptability and attitudes toward mBraze.

- Self-reported usability and user experience of the mBraze app measured with system usability scale (SUS).

- The interview on user acceptability and attitudes toward self-testing.

Karolinska University Hospital

MD, PhD

Behaviors and Mental Disorders

Quality of Life

Patients receive standard treatment protocol for breast cancer patients and additional oral and written information about adjuvant endocrine treatment.

Patients receive standard medical care and a brief behavioral intervention that targets patients' response and coping expectations while starting with adjuvant endocrine treatment.

Patients receive standard medical care and a comparable amount of therapist´s attention (common and unspecific factors) to the intervention group without targeting patients´ expectations.

SEPT is aimed to optimize patients' response expectations before the start of pharmacotherapy to prevent nocebo side effects during adjuvant endocrine treatment. SEPT is a three session cognitive-behavioural training. It includes psychoeducation about AET to provide a realistic view on AET, reduction of concerns about side effects and strengthening of necessity beliefs. Further contents are side effect management training and problem solving to enhance self-efficacy expectations about coping as well as imagination training to integrate positive aspects of medication into daily life.

Side effect prevention training (SEPT)

Supportive therapy includes common or unspecific factors such as elicitation of affect, a treatment context, empathy, reflective listening, and feeling understood. Supportive therapy thus provides a control condition for common factors and therapist attention, while lacking the specific intervention part. It will be delivered in the same frequency and at the same time points as the side effect prevention training (three individual sessions and three booster telephone calls).

Attention Control group (ACG)

Yvonne Nestoriuc, Prof. Dr.

Winfried Rief, Prof. Dr.

Ute-Susann Albert, Prof. Dr.

The purpose of this study is to evaluate a side effect prevention training (SEPT) that optimizes patients' response expectations before the start of adjuvant endocrine treatment (AET) to prevent nocebo side effects and enhance quality of life during longer term drug intake.

The majority of breast cancer patients discontinue today's standard adjuvant treatment (endocrine therapy) due to side effects and reduced quality of life. Thereby, most side effects are unspecific, thus, not related to the specific pharmacological action of the drug, but to the individual treatment context and patients´ expectations (nocebo effects). The aim of this study is to evaluate a side effect prevention training (SEPT) that optimizes patients' response expectations before the start of pharmacotherapy to prevent nocebo side effects during longer term drug intake. Using a randomized trial, we will study the time course of response expectations and side effects in breast cancer patients receiving either SEPT, standard medical care or an attention-control intervention ("supportive therapy") before the start of adjuvant endocrine therapy. We will analyze the effects of changing pre-treatment expectations on cancer-treatment related side effects, quality of life and adherence 3 and 6 months after the start of endocrine therapy. Moderator analyses will be used to determine predictors of non-specific medication side effects and patients that are at high risk of experiencing them. Furthermore, we will explore the mediating influence of coping behaviours, thereby providing insights into pathways of clinical nocebo effects. The study findings promise significant advances in the clinical application of nocebo research with strong implications for clinical and research practice.

Side Effect Prevention Training (SEPT) for Nocebo Effects in Breast Cancer Patients

Clinical Application of Nocebo Research: Optimizing Expectations of Breast Cancer Patients to Prevent Nocebo Side Effects and Decrease of Quality of Life During Adjuvant Endocrine Therapy (DFG, NE 1635/2-1)

Side Effects 3 and 6 months after the start of adjuvant endocrine therapy, controlled for baseline symptoms, staging, age, medication

Change in patients expectations from baseline/pre-intervention (expected average 2 weeks after surgery) to post-intervention (expected average 5 weeks after surgery) and prospective expectations 3 and 6 months after the start of adjuvant endocrine therapy

Change in anxiety and depression from baseline to 5 weeks after surgery to 3 months after the start of AET to 6 months after the start of AET

Change in Fear of Progression from baseline to 5 weeks after surgery to 3 months after the start of AET to 6 months after the start of AET

Change in Adherence Intention and Adherence from baseline to 5 weeks after surgery to 3 months after the start of AET to 6 months after the start of AET

Change in Quality of Life from baseline to 3 months after the start of adjuvant endocrine therapy to 6 months after the start of adjuvant endocrine therapy

Change in coping with Side Effects from 3 months after the start of adjuvant endocrine therapy to 6 months after the start of adjuvant endocrine therapy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Therapeutic Dose Monitoring (TDM) of Tamoxifen	NCT05133674	Breast Cancer Breast Carcinom... Breast Tumors Cancer of Breas... Malignant Neopl...	Tamoxifen 20 mg	18 Years -	Karolinska University Hospital
Side Effect Prevention Training (SEPT) for Nocebo Effects in Breast Cancer Patients	NCT01741883	Female Breast C...	Side effect pre... Attention Contr...	18 Years - 80 Years	Philipps University Marburg Medical Center
Side Effect Prevention Training (SEPT) for Nocebo Effects in Breast Cancer Patients	NCT01741883	Female Breast C...	Side effect pre... Attention Contr...	18 Years - 80 Years	Philipps University Marburg Medical Center

Spots Global Cancer Trial Database for adjuvant endocrine treatment