Clinical trial · Observational

Genetic Study of CYP2D6 Enzyme and Therapeutic Drug Monitoring of Tamoxifen

Genetic Study of CYP2D6 Enzyme and Therapeutic Drug Monitoring of Tamoxifen in Premenopausal Women With Breast Cancer

NCT03582865CI-TRIAL-00039364unknownClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

Aim of work: 1. To estimate the frequency of Cyp2D6\*1 and \*4 alleles in Egyptian patients maintained on tamoxifen (20 mg/day) for management of ER +ve breast cancer. 2. To measure levels of tamoxifen, 4-hydroxy tamoxifen, N-desmethyl-tamoxifen and 4- hydroxyl-N-desmethyl-tamoxifen (endoxifen) in the serum of these patients. 3. To correlate between the levels of tamoxifen/active metabolite enoxifen ratio and CYP2D6\*1,\*4 genotyping. 4. To investigate which is more valuable investigatory tool for prediction of the clinical outcome (response and/or toxicity) in these patients; either the measurements related to pharmacokinetics: tamoxifen/endoxifen levels or the pharmacogenetic analysis of CYP2D6 \*1,\*4.

Conditions

Conditions (1)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Breast Cancer	Malignant Breast Neoplasm	CURATED_EXACT	0.92

Interventions

Interventions (1)

Intervention	Type	Mapped drug	Match
Tamoxifen 20 mg	Drug	Tamoxifen	ALIAS

Design

Arms and outcomes

Arms (3)

label
responding
description
patients who received Tamoxifen 20 mg daily for at least 3 years with good response (no relapse) to tamoxifen. Both genotyping assessment and TDM of tamoxifen and its metabolites will be performed and correlated with the records. Follow up for these patients for further assessment of tamoxifen effectiveness will be carried out for 1- 2 years.
interventionNames
1. Drug: Tamoxifen 20 mg
label
relapse
description
patients who received Tamoxifen 20 mg daily for at least 3 years who were good responder to the drug but then the response has been diminished (relapse) and they have been shifted to another therapy. They will be exposed to genotyping study of CYP 2D6 to recognize the phenotyping style of that patient that may explain diminishing of response to tamoxifen therapy.
interventionNames
1. Drug: Tamoxifen 20 mg
label
tamoxifen resistant
description
patients who received Tamoxifen 20 mg daily for not more than 1 year with poor response to tamoxifen (early relapse) and clinically will be shifted to use another medication as they were diagnosed as tamoxifen resistant. Like the second group, they will be exposed to genotyping study of CYP2D6 with the same concept.

Eligibility

Eligibility (as posted)

Sex: Female
Minimum age: 20 Years
Maximum age: 50 Years

Show eligibility criteria text

Inclusion Criteria:

* Premenopausal patients will be included in this study, with hormone receptor positive tumors.
* The hormone receptor positive tumor is diagnosed by microscopic examination if ≥ 10% of the cells are positive for estrogen by immunohistochemistry analysis.
* All patients with normal hepatic and renal function, aspartate aminotransferase and alanine aminotransferase (≤2 upper normal limit) and serum creatinine (≤1.2 mg/dl).

Exclusion Criteria:

* Patients treated with other hormonal therapy, radiation or chemotherapy will be excluded from the study.
* Pregnant or breast feeding women will be excluded from the study.
* Patients who are taking drugs that are known to inhibit CYP2D6 activity as SSRIs will be excluded from the study.

References

Publications (20)

BACKGROUNDJohnston SR. New strategies in estrogen receptor-positive breast cancer. Clin Cancer Res. 2010 Apr 1;16(7):1979-87. doi: 10.1158/1078-0432.CCR-09-1823. Epub 2010 Mar 23. PMID 20332324
BACKGROUNDDavies C, Pan H, Godwin J, Gray R, Arriagada R, Raina V, Abraham M, Medeiros Alencar VH, Badran A, Bonfill X, Bradbury J, Clarke M, Collins R, Davis SR, Delmestri A, Forbes JF, Haddad P, Hou MF, Inbar M, Khaled H, Kielanowska J, Kwan WH, Mathew BS, Mittra I, Muller B, Nicolucci A, Peralta O, Pernas F, Petruzelka L, Pienkowski T, Radhika R, Rajan B, Rubach MT, Tort S, Urrutia G, Valentini M, Wang Y, Peto R; Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013 Mar 9;381(9869):805-16. doi: 10.1016/S0140-6736(12)61963-1. PMID 23219286
BACKGROUNDDowsett M, Cuzick J, Ingle J, Coates A, Forbes J, Bliss J, Buyse M, Baum M, Buzdar A, Colleoni M, Coombes C, Snowdon C, Gnant M, Jakesz R, Kaufmann M, Boccardo F, Godwin J, Davies C, Peto R. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol. 2010 Jan 20;28(3):509-18. doi: 10.1200/JCO.2009.23.1274. Epub 2009 Nov 30. PMID 19949017
BACKGROUNDGoldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, Senn HJ; Panel members. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol. 2013 Sep;24(9):2206-23. doi: 10.1093/annonc/mdt303. Epub 2013 Aug 4. PMID 23917950
BACKGROUNDLu WJ, Xu C, Pei Z, Mayhoub AS, Cushman M, Flockhart DA. The tamoxifen metabolite norendoxifen is a potent and selective inhibitor of aromatase (CYP19) and a potential lead compound for novel therapeutic agents. Breast Cancer Res Treat. 2012 May;133(1):99-109. doi: 10.1007/s10549-011-1699-4. Epub 2011 Aug 4. PMID 21814747