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

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.

Study Overview

• Status: Completed
• Conditions: Metastatic Breast Cancer, HER2 Negative Primary Tumor
• Intervention / Treatment: Drug: Trastuzumab - Emtansine

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Le Mans, France, 72000
    • Clinique Victor Hugo
  • Levallois-Perret, France, 92309
    • Institut de Cancérologie HARTMANN
  • Lille, France, 59020
    • Centre Oscar Lambret
  • Limoges, France, 87042
    • CHU de Limoges
  • Montpellier, France, 34298
    • Centre Val d'Aurelle - P. Lamarque
  • Paris, France, 75005
    • Institut Curie
  • Paris, France, 75475
    • Chu Saint-Louis
  • Saint-Cloud, France, SAINT-CLOUD
    • Institut Curie - Hôpital René HUGENIN
  • Vandœuvre-lès-Nancy, France, 54519
    • Institut de Cancerologie de Lorraine
  • Vandœuvre-lès-Nancy, France, 54519
    • Centre Catherine de Sienne

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: TDM-1	Drug: Trastuzumab - Emtansine

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
Progression-free survival		4 years
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
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)

Collaborators and Investigators

• Sponsor: Institut Curie

Publications and helpful links

General Publications

• Jacot W, Cottu P, Berger F, Dubot C, Venat-Bouvet L, Lortholary A, Bourgeois H, Bollet M, Servent V, Luporsi E, Espie M, Guiu S, D'Hondt V, Dieras V, Sablin MP, Brain E, Neffati S, Pierga JY, Bidard FC. Actionability of HER2-amplified circulating tumor cells in HER2-negative metastatic breast cancer: the CirCe T-DM1 trial. Breast Cancer Res. 2019 Nov 14;21(1):121. doi: 10.1186/s13058-019-1215-z.

Study record dates

Study Major Dates

• Study Start (Actual): November 7, 2013
• Primary Completion (Actual): February 13, 2018
• Study Completion (Actual): January 21, 2019

Study Registration Dates

• First Submitted: October 17, 2013
• First Submitted That Met QC Criteria: November 1, 2013
• First Posted (Estimated): November 4, 2013

Study Record Updates

• Last Update Posted (Estimated): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Metastatic breast cancer; HER2 negative primary tumor; CTC HER2 positive
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Macrolides; Lactones; Lactams, Macrocyclic; Macrocyclic Compounds; Maytansine; Trastuzumab; Ado-Trastuzumab Emtansine
• Other Study ID Numbers: IC 2013-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO