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

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+

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.

Study Overview

• Status: Completed
• Conditions: Non Metastatic Breast Cancer
• Intervention / Treatment: Drug: tamoxifen

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lyon, France, 69000
    • Centre Léon Bérard
  • Paris, France
    • Institut Curie
  • Saint Herblain, France, 44805
    • Institut de cancerologie de l'ouest (ICO)

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:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tamoxifene	Drug: tamoxifen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	5 weeks

Collaborators and Investigators

• Sponsor: Institut Cancerologie de l'Ouest

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2009
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: October 11, 2010
• First Submitted That Met QC Criteria: October 12, 2010
• First Posted (Estimate): October 13, 2010

Study Record Updates

• Last Update Posted (Actual): March 12, 2021
• Last Update Submitted That Met QC Criteria: March 10, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacogenetic; Tamoxifen,; Breat Cancer; non metastatic breast cancer, HR +
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen
• Other Study ID Numbers: BRD 08/11-A