Pharmacology of Adjuvant Hormonotherapy in Breast Cancer (PHACS)

Breast Cancer Adjuvant Hormonotherapy : Tamoxifen and the Anti-aromatases Pharmacokinetics, Correlation With the Pharmacogenetic Characteristics PHACS Protocol : Pharmacology of Adjuvant Hormonotherapy in Breast Cancer

This is a biomedical study of interventional type, multicenter, inter-regional.

Patients with hormono-depending breast cancer, for which an indication of adjuvant hormonotherapy treatment (according to the current treatments) was retained, will be enrolled in this study. The main objective is to estimate the correlations between pharmacokinetic and pharmacogenetic parameters of adjuvant hormonal breast cancer treatment, during the first 3 years.

Study Overview

• Status: Completed
• Conditions: Hormono-depending Adjuvant Breast Cancer
• Intervention / Treatment: Drug: Tamoxifen, Letrozole, Anastrozole or Exemestane

• Study Type: Interventional
• Enrollment (Actual): 2000
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Agen, France, 47000
    • Clinique Calabet
  • Albi, France, 81030
    • Clinique Claude Bernard
  • Auch, France, 32008
    • Centre Hospitalier d'Auch
  • Bordeaux, France, 33076
    • Institut Bergonié
  • Bordeaux, France, 33000
    • Clinique Tivoli
  • Bordeaux, France, 33000
    • CHU de Bordeaux
  • Bordeaux, France, 33077
    • Polyclinique Bordeaux Nord
  • Brive La Gaillarde, France, 19312
    • Centre Hospitalier de Brive
  • Cahors, France, 46005
    • Centre Hospitalier de Cahors
  • Castres, France, 81108
    • Centre Hospitalier Intercommunal de Castres-Mazamet
  • Limoges, France, 87042
    • Hôpital Dupuytren CHU Limoges
  • Mont de Marsan, France, 40024
    • Centre Hospitalier de Mont de Marsan
  • Montauban, France, 82013
    • Centre Hospitalier de Montauban
  • Montpellier, France, 34298
    • Centre Val D'Aurelle
  • Nîmes, France, 30029
    • Hôpital Carémeau CHU NIMES
  • Pau, France, 64000
    • Centre Hospitalier de Pau
  • Perpignan, France, 66000
    • Centre Catalan d'Oncologie
  • Rodez, France, 12000
    • Centre Hospitalier de Rodez
  • Tarbes, France, 65000
    • Polyclinique de l'Ormeau
  • Toulouse, France, 31059
    • CHU de Rangueil
  • Toulouse, France, 31052
    • Claudius Regaud
  • Toulouse, France, 31076
    • Clinique Pasteur - Département d'Oncologie Médicale
  • Toulouse, France, 31300
    • Clinique Pasteur - Département de Radiothérapie
  • Toulouse, France, 31400
    • Clinique Saint-Jean du Languedoc

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Patient of more than 18 years old (menopaused or not)
2. Invasive breast cancer non-metastatic locally controlled by surgery with or without radiotherapy. Previous treatment with chemotherapy is allowed including trastuzumab
3. Cancer hormone-expressing ER and / or PR (> 10% tumor cells in Technical HIC)
4. Having a staging exploring bone, liver, lung and showing no abnormality secondary (for sub-centimeter tumors, the staging is not necessary)
5. WHO <2
6. Before the initiation of adjuvant hormonal therapy (tamoxifen, anastrozole, letrozole or exemestane) and whatever the approach chosen by the investigator (5 years of tamoxifen, 5 years of anti-aromatase or sequential patterns)
7. signed Consent collected before any specific procedure in the study
8. Patient member in a national insurance scheme.

Exclusion Criteria:

1. Patient previously treated for breast cancer receiving hormonal therapy with tamoxifen, anastrozole, letrozole or exemestane regardless of the scheme
2. Metastatic Breast cancer
3. History of another cancer diagnosed within 5 years before or uncontrolled except carcinoma in situ of cervix carcinoma, nonmelanoma skin, breast cancer (in this case, treatment with hormone therapy should be stopped for at least 6 months)
4. Any other medical or psychiatric condition or laboratory abnormality severe acute or chronic making the inclusion of the patient in the study inappropriate in the opinion of the investigator
5. Patient unable to follow procedures, visits, examinations described in the study
6. Pregnant women or nursing mothers can not participate in the study
7. Women of childbearing age must use effective contraception at study entry and up to at least three months after the end of treatment
8. Patient under legal guardianship

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Tamoxifen, Anastrozole, letrozole, Exemestane; Current hormonotherapy treatment in hormono dependent breast cancer	Drug: Tamoxifen, Letrozole, Anastrozole or Exemestane; Tamoxifen 20 mg/day during 5 years Létrozole 2.5 mg/day during 5 years Anastrozole 1 mg/day during 5 years Exémestane 25 mg/day during 5 years

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between pharmacokinetic and pharmacogenetic parameters	To estimate the correlations between pharmacokinetic and pharmacogenetic parameters of hormonal adjuvant breast cancer treatment during the first 3 years.	9 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To estimate the relation between plasmatic concentrations, pharmacogenetic characteristic and adverse effects.	9 years
To estimate the relation between the genetic polymorphisms and premature relapses in the first 3 years of treatment	9 years
To estimate the link between plasmatic concentrations and the premature relapse (in the first 3 years)	9 years
To estimate the declared therapeutic observance to the real exposure at the treatment measured by plasmatic concentrations.	9 years
appearance auto-antibody and correlate to the clinical data	9 years

Collaborators and Investigators

• Sponsor: Institut Claudius Regaud
• Investigators: Principal Investigator: Henri Roché, Pr, Institut Claudius Regaud

Publications and helpful links

General Publications

• Puszkiel A, Arellano C, Vachoux C, Evrard A, Le Morvan V, Boyer JC, Robert J, Delmas C, Dalenc F, Debled M, Venat-Bouvet L, Jacot W, Dohollou N, Bernard-Marty C, Laharie-Mineur H, Filleron T, Roche H, Chatelut E, Thomas F, White-Koning M. Model-Based Quantification of Impact of Genetic Polymorphisms and Co-Medications on Pharmacokinetics of Tamoxifen and Six Metabolites in Breast Cancer. Clin Pharmacol Ther. 2021 May;109(5):1244-1255. doi: 10.1002/cpt.2077. Epub 2020 Nov 10.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2010
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: May 18, 2010
• First Submitted That Met QC Criteria: May 19, 2010
• First Posted (Estimate): May 20, 2010

Study Record Updates

• Last Update Posted (Actual): March 2, 2018
• Last Update Submitted That Met QC Criteria: March 1, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: breast cancer; Pharmacokinetics; tamoxifen; Pharmacogenetic; Observance; anti-aromatases; pharmacodynamy
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Letrozole; Tamoxifen; Anastrozole; Exemestane
• Other Study ID Numbers: 09 SEIN 09