Clinical trial NCT01975142: Validity of HER2-amplified Circulating Tumor Cells to Select Metastatic Breast Cancer Considered HER2-negative for Trastuzumab-emtansine (T-DM1) Treatment.
Official title: Validity of HER2-amplified Circulating Tumor Cells to Select Metastatic Breast Cancer Considered HER2-negative for Trastuzumab-emtansine (T-DM1) Treatment.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer, HER2 Negative Primary Tumor
Keywords: Metastatic breast cancer
HER2 negative primary tumor
CTC HER2 positive
Lead sponsor: Institut Curie
Sponsor class: OTHER
First posted: 2013-11-03
Enrollment: 155
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Tumor response rate to T-DM1 in patients with HER2 amplified circulating tumor cells
timeFrame: Until disease progression (estimated duration : 1 year)
Secondary outcomes:
measure: Detection rate of HER2 amplified circulating tumor cells, heterogeneity rate between circulating tumor cells and correlations with patient characteristics
timeFrame: 1 month
measure: Technical failure rate and reproducibility of HER2 FISH on circulating tumor cells
timeFrame: 1 month
measure: Correlation between HER2 FISH and immunofluorescence on circulating tumor cells
timeFrame: 1 month
measure: Progression-free survival
timeFrame: 4 years
measure: Disease control rate (responses and stable diseases)
timeFrame: Until disease progression (estimated duration : 1 year)
measure: Correlation between treatment efficacy and HER2 FISH results (level of amplification, absolute number and percentage of amplified cells)
timeFrame: Until disease progression (estimated duration : 1 year)
measure: Changes in CTC numbers during treatment
timeFrame: Until disease progression (estimated duration : 1 year)
measure: Circulating tumor DNA before and during treatment
timeFrame: Until disease progression (estimated duration : 1 year)
measure: Treatment toxicity
timeFrame: Until disease progression (estimated duration : 1 year)
Other outcomes:
Locations:
city: Le Mans
country: France
facility: Clinique Victor Hugo
city: Levallois-perret
country: France
facility: Institut de Cancérologie HARTMANN
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: Chu de Limoges
city: Montpellier
country: France
facility: Centre Val d'Aurelle - P. Lamarque
city: Paris
country: France
facility: Institut Curie
city: Paris
country: France
facility: Chu Saint-Louis
city: Saint-cloud
country: France
facility: Institut Curie - Hôpital René HUGENIN
city: Vandoeuvre Les Nancy
country: France
facility: Centre Catherine de Sienne
city: Vandoeuvre Les Nancy
country: France
facility: Institut de Cancérologie de Lorraine
Study officials:
References:
citation: 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.