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Biological Response to Tamoxifen (TAM) in Patients With Breast Cancer Non Metastatic RH+ (TAM)

Primary Purpose

Non Metastatic Breast Cancer

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
tamoxifen
Sponsored by
Institut Cancerologie de l'Ouest
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional screening trial for Non Metastatic Breast Cancer focused on measuring Tamoxifen,, Breat Cancer, Pharmacogenetic, non metastatic breast cancer, HR +

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult Females (≥ 18 years), with effective contraception. The contraceptive should not use estrogen to a derivative. It must be continued during treatment with tamoxifen for at least two months after his arrest.
  • Histologically confirmed diagnosis of invasive breast cancer, previously untreated. Patients have been supported for a breast cancer may be included if a period of at least 2 years between the last systemic treatment of inclusion in the study.
  • Primary tumor hormonopositive: ER and / or PR ≥ 50% by immunohistochemistry.
  • Lack of HER2 overexpression
  • Palpable primary tumor or greater than or equal to 20 mm in diameter, measured by ultrasound
  • Patient scheduled to undergo breast cancer surgery
  • No metastases
  • Clinical Stage M0
  • Performance index ≤ 1 (OMS)
  • Neutrophils WBC > or = 1500 / mm3, Platelets > or = 100 000/mm3 Hemoglobin ≥10 g/dL
  • Normal liver function: bilirubin ≤ 1.5 x ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases).
  • Normal renal function (creatinine ≤ 1.5 mg / dL or creatinine clearance ≥ 60 mL / min)
  • Cardiac function (MUGA scan or ultrasound February> 55%) and lung function, 5.2.2 Criteria related to participation in the study:
  • Patient affiliated to social security, Patient has signed and dated consent

Non-Inclusion Criteria:

  1. Pregnant or Breastfeeding women
  2. Use of St. John's Wort (herbal tea ...) within 5 days before starting treatment
  3. Consumption of grapefruit juice in the last 5 days of starting treatment
  4. Congenital galactosemia
  5. Glucose and galactose malabsorption
  6. Lactase deficiency
  7. Co-medications that may interfere with cytochrome P450:
  8. Ongoing Enzyme inducers:

    • Antiepileptic drugs: carbamazepine, phenobarbital, phenytoin
    • Antinfectieux: rifampin, rifabutin, névrirapine, griséofilvine, efavirenz
  9. Ongoing Enzyme Inhibitors:

    • Inhibitors of serotonin reuptake: fluoxetine, paroxetine
    • Thioridazine. Quinidine
    • Amiodarone
    • Ca antagonists: diltiazem, verapamil
    • azole antifungals ketoconazole, fluconazole, miconazole.
    • No protease inhibitors: ritonavir, nelfinavir, amprenavir, indinavir.
    • Macrolides: erythromycin, clarithromycin, josamycin

Sites / Locations

  • Centre Léon Berard
  • Institut Curie
  • Institut de Cancerologie de l'Ouest (ICO)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tamoxifene

Arm Description

Outcomes

Primary Outcome Measures

Evaluate the response to Tamoxifen treatment, in preoperative situations (immediately operable patients) in patients with positive Hormone Receptors (HR+) non-metastatic breast cancer
The primary endpoint is the determination of the variation in the KI-67 expression, a marker of cell proliferation, at the tumour level between the initial biopsy (T0) and after 5 weeks of tamoxifen treatment, in relation to cytochrome 2D6 polymorphisms. A 50% geometric reduction in KI-67 expression at 5 to 7 weeks should be considered as a major response

Secondary Outcome Measures

Full Information

First Posted
October 11, 2010
Last Updated
March 10, 2021
Sponsor
Institut Cancerologie de l'Ouest
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1. Study Identification

Unique Protocol Identification Number
NCT01220076
Brief Title
Biological Response to Tamoxifen (TAM) in Patients With Breast Cancer Non Metastatic RH+
Acronym
TAM
Official Title
Phase II Study Evaluating According to the Polymorphism of CYP2D6, the Rate of Biological Response to Treatment With Tamoxifen (TAM) Administered in Pre-operative Situation in Patients With Breast Cancer Non Metastatic HR+
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Completed
Study Start Date
September 2009 (Actual)
Primary Completion Date
October 2016 (Actual)
Study Completion Date
October 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Cancerologie de l'Ouest

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The biological response to treatment with tamoxifen in the preoperative situation is studying in this protocol. This study will enrolls patients with non-metastatic breast cancer HR +. The relationship between the CYP2D6 polymorphism, pharmacokinetics and biological efficacy of TAM will be studied.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non Metastatic Breast Cancer
Keywords
Tamoxifen,, Breat Cancer, Pharmacogenetic, non metastatic breast cancer, HR +

7. Study Design

Primary Purpose
Screening
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
140 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tamoxifene
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
tamoxifen
Primary Outcome Measure Information:
Title
Evaluate the response to Tamoxifen treatment, in preoperative situations (immediately operable patients) in patients with positive Hormone Receptors (HR+) non-metastatic breast cancer
Description
The primary endpoint is the determination of the variation in the KI-67 expression, a marker of cell proliferation, at the tumour level between the initial biopsy (T0) and after 5 weeks of tamoxifen treatment, in relation to cytochrome 2D6 polymorphisms. A 50% geometric reduction in KI-67 expression at 5 to 7 weeks should be considered as a major response
Time Frame
5 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult Females (≥ 18 years), with effective contraception. The contraceptive should not use estrogen to a derivative. It must be continued during treatment with tamoxifen for at least two months after his arrest. Histologically confirmed diagnosis of invasive breast cancer, previously untreated. Patients have been supported for a breast cancer may be included if a period of at least 2 years between the last systemic treatment of inclusion in the study. Primary tumor hormonopositive: ER and / or PR ≥ 50% by immunohistochemistry. Lack of HER2 overexpression Palpable primary tumor or greater than or equal to 20 mm in diameter, measured by ultrasound Patient scheduled to undergo breast cancer surgery No metastases Clinical Stage M0 Performance index ≤ 1 (OMS) Neutrophils WBC > or = 1500 / mm3, Platelets > or = 100 000/mm3 Hemoglobin ≥10 g/dL Normal liver function: bilirubin ≤ 1.5 x ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases). Normal renal function (creatinine ≤ 1.5 mg / dL or creatinine clearance ≥ 60 mL / min) Cardiac function (MUGA scan or ultrasound February> 55%) and lung function, 5.2.2 Criteria related to participation in the study: Patient affiliated to social security, Patient has signed and dated consent Non-Inclusion Criteria: Pregnant or Breastfeeding women Use of St. John's Wort (herbal tea ...) within 5 days before starting treatment Consumption of grapefruit juice in the last 5 days of starting treatment Congenital galactosemia Glucose and galactose malabsorption Lactase deficiency Co-medications that may interfere with cytochrome P450: Ongoing Enzyme inducers: Antiepileptic drugs: carbamazepine, phenobarbital, phenytoin Antinfectieux: rifampin, rifabutin, névrirapine, griséofilvine, efavirenz Ongoing Enzyme Inhibitors: Inhibitors of serotonin reuptake: fluoxetine, paroxetine Thioridazine. Quinidine Amiodarone Ca antagonists: diltiazem, verapamil azole antifungals ketoconazole, fluconazole, miconazole. No protease inhibitors: ritonavir, nelfinavir, amprenavir, indinavir. Macrolides: erythromycin, clarithromycin, josamycin
Facility Information:
Facility Name
Centre Léon Berard
City
Lyon
ZIP/Postal Code
69000
Country
France
Facility Name
Institut Curie
City
Paris
Country
France
Facility Name
Institut de Cancerologie de l'Ouest (ICO)
City
Saint Herblain
ZIP/Postal Code
44805
Country
France

12. IPD Sharing Statement

Learn more about this trial

Biological Response to Tamoxifen (TAM) in Patients With Breast Cancer Non Metastatic RH+

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