Circulating miRNAs as Biomarkers of Hormone Sensitivity in Breast Cancer (MIRHO)

Circulating miRNAs as Biomarkers of Hormone Sensitivity in Breast Cancer? Pilot Study.

This is a biomedical and prospective study of interventional type. The trial will include 29 patients over a period of 15 months + 24 months of follow up maximum.

The study will be conduct in womens with metastatic invasive breast cancer or locally advanced breast cancer and for which treatment with tamoxifen or anti aromatase (first line hormone therapy for metastatic breast cancer) is indicated.

The main objective of this pilot study is to evaluate the feasibility to detect in the circulating blood of patients, before treatment (T0), the presence of the fifteen tissular microRNAs described in preclinical studies as possibly involved in hormone resistance/sensitivity.

In parallel of the detection of these specific miRNAs, we will conduct a larger scale analysis of circulating miRNAs in these patients before (T = 0) and after one month of treatment (T28).

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Tamoxifen, Letrozole , Anastrozole, Exemestane

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Montpellier, France, 34298
    • Centre Val d'Aurelle - Paul Lamarque
  • Toulouse, France, 31052
    • Institut Claudius Regaud Toulouse

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. Women of more than 18 years old (menopausal or not)

2. Women with metastatic invasive breast cancer or locally advanced (without surgical project), for which treatment with tamoxifen or anti aromatase

   +/- LH-RH agonist, is indicated (anti-aromatase prescribed for menopausal womens; tamoxifen prescribed for both menopausal, pre menopausal or not menopausal womens).

3. Cancer hormone-expressing estrogen receptor (ER) and / or progesterone receptor (PR) (>= 10% of tumor cells by IHC technique).

   Cancer HER2 negative.

4. Evaluable disease (measurable according RECIST criteria or not)
5. Any previous adjuvant hormone therapy should be discontinued for at least 21 days.
6. One or two prior metastatic lines of chemotherapy are allowed
7. General status WHO 0-2
8. The women of childbearing age must use an effective contraception for the duration of the study
9. Informed consent obtained and signed before any specific study procedure
10. Patient member in a national insurance scheme

Exclusion Criteria:

1. Patient already treated with hormone therapy or not having stopped the previous adjuvant hormone therapy for at least 21 days.
2. Prescription of chemotherapy and / or other targeted therapy (other than hormone therapy) for the treatment of the breast cancer
3. Any previous hormone therapy for metastatic or locally advanced (without surgical project) breast cancer
4. Known hypercalcaemia before miRNA dosage at T=0 requiring immediate biphosphonate therapy
5. Any other medical or psychiatric condition or severe or chronic laboratory abnormality making the the inclusion of the patient in the study inappropriate in the opinion of the investigator.
6. Patient unable to follow procedures, visits, examinations described in the study.
7. Pregnant women or nursing mothers will not participate in the study.
8. Patients 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
Experimental: hormone therapy treatment; Tamoxifen 20 mg/day, Letrozole 2.5 mg/day, Anastrozole 1 mg/day, Exemestane 25mg/day	Drug: Tamoxifen, Letrozole , Anastrozole, Exemestane; Current first line metastatic hormone therapy treatment in hormone dependent breast cancer : Tamoxifen 20 mg/day, Letrozole 2.5 mg/day, Anastrozole 1 mg/day, Exemestane 25mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of patients for which specific tissular miRNAs are detected in blood before treatment (D0)	MiRNAs will be quantified in plasma using qPCR (quantitative Polymerase Chain Reaction) with the kit "miScriptSYBR Green PCR" (Qiagen)	1 time point (D0) over a period of 39 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Analysis of the larger-scale circulating miRNAs in plasma of these patients before (D0) and after one month (D28) of treatment with tamoxifen or anti aromatase	2 time points (D0 and D28) over a period of 39 months (3 years and 3 months)
Correlation between the specific miRNAs initial expression and the appearance of an objective response or clinical benefit of hormone therapy and the time to progression	39 months (3 years and 3 months)
Rate of objective responses, defined as the number of patients with a complete or partial response.	39 months (3 years and 3 months)
The time to progression, defined as the time from patient inclusion to the date of the first documented tumor progression	39 months (3 years and 3 months)

Collaborators and Investigators

• Sponsor: Institut Claudius Regaud
• Investigators: Principal Investigator: Florence DALENCr, PhD, Institut Claudius Regaud

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2012
• Primary Completion (Actual): January 28, 2016
• Study Completion (Actual): January 28, 2016

Study Registration Dates

• First Submitted: June 4, 2012
• First Submitted That Met QC Criteria: June 5, 2012
• First Posted (Estimate): June 6, 2012

Study Record Updates

• Last Update Posted (Actual): March 5, 2018
• Last Update Submitted That Met QC Criteria: March 2, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: biomarkers; hormone therapy; Breast cancer,; hormonotherapy,; miRNAs,
• 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: 11SEIN12

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No