Therapeutic Dose Monitoring (TDM) of Tamoxifen

NCT05133674 | Unknown Phase 2

• 1 other identifier: TDM of TAM
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer; Breast Carcinoma; Breast Tumors; Cancer of Breast; Malignant Neoplasm of Breast

Keywords

Adjuvant Tamoxifen; Endoxifen; Patient reported outcomes; Adjuvant endocrine treatment; Selective Estrogen Receptor Modulators

Outcome Measures

Primary Outcomes (2)

• To validate the rhelise™ kit for monitoring tamoxifen, 4-hydroxytamoxifen and Z-endoxifen among patients recommended or who have ongoing adjuvant tamoxifen.

  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).

  At at inclusion (baseline) for each participant.

• To validate the rhelise™ kit for monitoring tamoxifen, 4-hydroxytamoxifen and Z-endoxifen among patients recommended or who have ongoing adjuvant tamoxifen.

  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).

  At week 3 after inclusion for each participant.

Secondary Outcomes (7)

• 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.

• 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.

• 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

• To validate the user experience of the mBraze app.

  at 3 weeks.

Study Arms (1)

0

EXPERIMENTAL

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

Drug: Tamoxifen 20 mg

Interventions

Tamoxifen 20 mg DRUG

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.

0

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karolinska University Hospital: lead

Study Sites (1)

Karolinska University Hospital

Stockholm, 171 76, Sweden

Location

Related Publications (14)

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG); Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, Wang YC, Dowsett M, Ingle J, Peto R. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet. 2011 Aug 27;378(9793):771-84. doi: 10.1016/S0140-6736(11)60993-8. Epub 2011 Jul 28.

  PMID: 21802721 BACKGROUND

• Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015 Oct 3;386(10001):1341-1352. doi: 10.1016/S0140-6736(15)61074-1. Epub 2015 Jul 23.

  PMID: 26211827 BACKGROUND

• Eriksson M, Eklund M, Borgquist S, Hellgren R, Margolin S, Thoren L, Rosendahl A, Lang K, Tapia J, Backlund M, Discacciati A, Crippa A, Gabrielson M, Hammarstrom M, Wengstrom Y, Czene K, Hall P. Low-Dose Tamoxifen for Mammographic Density Reduction: A Randomized Controlled Trial. J Clin Oncol. 2021 Jun 10;39(17):1899-1908. doi: 10.1200/JCO.20.02598. Epub 2021 Mar 18.

  PMID: 33734864 BACKGROUND

• He W, Fang F, Varnum C, Eriksson M, Hall P, Czene K. Predictors of Discontinuation of Adjuvant Hormone Therapy in Patients With Breast Cancer. J Clin Oncol. 2015 Jul 10;33(20):2262-9. doi: 10.1200/JCO.2014.59.3673. Epub 2015 Jun 1.

  PMID: 26033800 BACKGROUND

• Madlensky L, Natarajan L, Tchu S, Pu M, Mortimer J, Flatt SW, Nikoloff DM, Hillman G, Fontecha MR, Lawrence HJ, Parker BA, Wu AH, Pierce JP. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes. Clin Pharmacol Ther. 2011 May;89(5):718-25. doi: 10.1038/clpt.2011.32. Epub 2011 Mar 23.

  PMID: 21430657 BACKGROUND

• Fabian CJ. Will a Low-Dose Option Improve Uptake of Tamoxifen for Breast Cancer Risk Reduction? J Clin Oncol. 2019 Jul 1;37(19):1595-1597. doi: 10.1200/JCO.19.00656. Epub 2019 May 13. No abstract available.

  PMID: 31082270 BACKGROUND

• Smith SG, Sestak I, Forster A, Partridge A, Side L, Wolf MS, Horne R, Wardle J, Cuzick J. Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis. Ann Oncol. 2016 Apr;27(4):575-90. doi: 10.1093/annonc/mdv590. Epub 2015 Dec 8.

  PMID: 26646754 BACKGROUND

• Thoren L, Lindh JD, Ackehed G, Kringen MK, Hall P, Bergh J, Molden E, Margolin S, Eliasson E. Impairment of endoxifen formation in tamoxifen-treated premenopausal breast cancer patients carrying reduced-function CYP2D6 alleles. Br J Clin Pharmacol. 2021 Mar;87(3):1243-1252. doi: 10.1111/bcp.14500. Epub 2020 Aug 9.

  PMID: 32713032 BACKGROUND

• Borges S, Desta Z, Li L, Skaar TC, Ward BA, Nguyen A, Jin Y, Storniolo AM, Nikoloff DM, Wu L, Hillman G, Hayes DF, Stearns V, Flockhart DA. Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther. 2006 Jul;80(1):61-74. doi: 10.1016/j.clpt.2006.03.013.

  PMID: 16815318 BACKGROUND

• Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005 Jan 5;97(1):30-9. doi: 10.1093/jnci/dji005.

  PMID: 15632378 BACKGROUND

• Ferraldeschi R, Newman WG. The Impact of CYP2D6 Genotyping on Tamoxifen Treatment. Pharmaceuticals (Basel). 2010 Apr 15;3(4):1122-1138. doi: 10.3390/ph3041122.

  PMID: 27713292 BACKGROUND

• Cronin-Fenton DP, Damkier P. Tamoxifen and CYP2D6: A Controversy in Pharmacogenetics. Adv Pharmacol. 2018;83:65-91. doi: 10.1016/bs.apha.2018.03.001. Epub 2018 May 7.

  PMID: 29801584 BACKGROUND

• Sanchez-Spitman AB, Swen JJ, Dezentje VO, Moes DJAR, Gelderblom H, Guchelaar HJ. Effect of CYP2C19 genotypes on tamoxifen metabolism and early-breast cancer relapse. Sci Rep. 2021 Jan 11;11(1):415. doi: 10.1038/s41598-020-79972-x.

  PMID: 33432065 BACKGROUND

• Bergqvist J, Lundstrom S, Wengstrom Y. Patient interactive digital support for women with adjuvant endocrine therapy in order to increase compliance and quality of life. Support Care Cancer. 2021 Jan;29(1):491-497. doi: 10.1007/s00520-020-05476-z. Epub 2020 May 13.

  PMID: 32405965 BACKGROUND

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Elham Hedayati, MD PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: October 7, 2021
• First Posted: November 24, 2021
• Study Start: April 4, 2022
• Primary Completion: December 31, 2022
• Study Completion: March 1, 2023
• Last Updated: May 25, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)