Validity of HER2-amplified Circulating Tumor Cells to Select Metastatic Breast Cancer Considered HER2-negative for Trastuzumab-emtansine (T-DM1) Treatment.

Study Overview
=================
Brief Summary
-----------------
Patients with metastatic breast cancer considered HER2 negative are screened for HER2-amplified circulating tumor cells. If at least HER2-amplified circulating tumor cell is detected, patients are treated by Trastuzumab - Emtansine (T-DM1) in a single arm phase II with an adaptive design.

Official Title
-----------------
Validity of HER2-amplified Circulating Tumor Cells to Select Metastatic Breast Cancer Considered HER2-negative for Trastuzumab-emtansine (T-DM1) Treatment.

Conditions
-----------------
Metastatic Breast Cancer, HER2 Negative Primary Tumor

Intervention / Treatment
-----------------
* Drug: Trastuzumab - Emtansine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion criteria for screening: Breast adenocarcinoma considered HER2-negative on the primary tumour or unknown status HER2 A least one metastatic site and/or inoperable loco-regional relapse Measurable disease (RECIST v1.1) Age from 18 to 75 years Performance status of 0-2 Efficient contraceptive in non-menopause women Inclusion criteria for treatment : At least 1 (Cohort  L ) or 3 (cohort  H ) HER2 amplified CTC Performance status of 0-2 Adequate cardiac function Adequate hematological and biochemical blood tests Exclusion Criteria: Life expectancy of less than 3 months Previous history of any other stage III or IV invasive cancer Male breast cancer Uncontrolled brain metastases Significant cumulated exposure to anthracyclines Current or previous significant history of cardio-vascular/pulmonary disease Previous use of trastuzumab

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TDM-1<br> | Drug: Trastuzumab - Emtansine<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor response rate to T-DM1 in patients with HER2 amplified circulating tumor cells | Assessment every 6 weeks. | Until disease progression (estimated duration : 1 year) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Detection rate of HER2 amplified circulating tumor cells, heterogeneity rate between circulating tumor cells and correlations with patient characteristics |  | 1 month | 
| Technical failure rate and reproducibility of HER2 FISH on circulating tumor cells |  | 1 month | 
| Correlation between HER2 FISH and immunofluorescence on circulating tumor cells |  | 1 month | 
| Progression-free survival |  | 4 years | 
| Disease control rate (responses and stable diseases) |  | Until disease progression (estimated duration : 1 year) | 
| Correlation between treatment efficacy and HER2 FISH results (level of amplification, absolute number and percentage of amplified cells) |  | Until disease progression (estimated duration : 1 year) | 
| Changes in CTC numbers during treatment |  | Until disease progression (estimated duration : 1 year) | 
| Circulating tumor DNA before and during treatment |  | Until disease progression (estimated duration : 1 year) | 
| Treatment toxicity | Toxicity of the treatment from first intake until disease progression | Until disease progression (estimated duration : 1 year) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metastatic breast cancer, HER2 negative primary tumor, CTC HER2 positive