Validity of HER2-amplified Circulating Tumor Cells to Select Metastatic Breast Cancer Considered HER2-negative for Trastuzumab-emtansine (T-DM1) Treatment.
Primary Purpose
Metastatic Breast Cancer, HER2 Negative Primary Tumor
Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Trastuzumab - Emtansine
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer, HER2 Negative Primary Tumor focused on measuring Metastatic breast cancer, HER2 negative primary tumor, CTC HER2 positive
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
Sites / Locations
- Clinique Victor Hugo
- Institut de Cancérologie HARTMANN
- Centre Oscar Lambret
- Chu de Limoges
- Centre Val d'Aurelle - P. Lamarque
- Institut Curie
- Chu Saint-Louis
- Institut Curie - Hôpital René HUGENIN
- Centre Catherine de Sienne
- Institut de Cancérologie de Lorraine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TDM-1
Arm Description
Outcomes
Primary Outcome Measures
Tumor response rate to T-DM1 in patients with HER2 amplified circulating tumor cells
Assessment every 6 weeks.
Secondary Outcome Measures
Detection rate of HER2 amplified circulating tumor cells, heterogeneity rate between circulating tumor cells and correlations with patient characteristics
Technical failure rate and reproducibility of HER2 FISH on circulating tumor cells
Correlation between HER2 FISH and immunofluorescence on circulating tumor cells
Progression-free survival
Disease control rate (responses and stable diseases)
Correlation between treatment efficacy and HER2 FISH results (level of amplification, absolute number and percentage of amplified cells)
Changes in CTC numbers during treatment
Circulating tumor DNA before and during treatment
Treatment toxicity
Toxicity of the treatment from first intake until disease progression
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01975142
Brief Title
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
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
November 7, 2013 (Actual)
Primary Completion Date
February 13, 2018 (Actual)
Study Completion Date
January 21, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Curie
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Breast Cancer, HER2 Negative Primary Tumor
Keywords
Metastatic breast cancer, HER2 negative primary tumor, CTC HER2 positive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
155 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TDM-1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Trastuzumab - Emtansine
Primary Outcome Measure Information:
Title
Tumor response rate to T-DM1 in patients with HER2 amplified circulating tumor cells
Description
Assessment every 6 weeks.
Time Frame
Until disease progression (estimated duration : 1 year)
Secondary Outcome Measure Information:
Title
Detection rate of HER2 amplified circulating tumor cells, heterogeneity rate between circulating tumor cells and correlations with patient characteristics
Time Frame
1 month
Title
Technical failure rate and reproducibility of HER2 FISH on circulating tumor cells
Time Frame
1 month
Title
Correlation between HER2 FISH and immunofluorescence on circulating tumor cells
Time Frame
1 month
Title
Progression-free survival
Time Frame
4 years
Title
Disease control rate (responses and stable diseases)
Time Frame
Until disease progression (estimated duration : 1 year)
Title
Correlation between treatment efficacy and HER2 FISH results (level of amplification, absolute number and percentage of amplified cells)
Time Frame
Until disease progression (estimated duration : 1 year)
Title
Changes in CTC numbers during treatment
Time Frame
Until disease progression (estimated duration : 1 year)
Title
Circulating tumor DNA before and during treatment
Time Frame
Until disease progression (estimated duration : 1 year)
Title
Treatment toxicity
Description
Toxicity of the treatment from first intake until disease progression
Time Frame
Until disease progression (estimated duration : 1 year)
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
Clinique Victor Hugo
City
Le Mans
ZIP/Postal Code
72000
Country
France
Facility Name
Institut de Cancérologie HARTMANN
City
Levallois-perret
ZIP/Postal Code
92309
Country
France
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59020
Country
France
Facility Name
Chu de Limoges
City
Limoges
ZIP/Postal Code
87042
Country
France
Facility Name
Centre Val d'Aurelle - P. Lamarque
City
Montpellier
ZIP/Postal Code
34298
Country
France
Facility Name
Institut Curie
City
Paris
ZIP/Postal Code
75005
Country
France
Facility Name
Chu Saint-Louis
City
Paris
ZIP/Postal Code
75475
Country
France
Facility Name
Institut Curie - Hôpital René HUGENIN
City
Saint-cloud
ZIP/Postal Code
SAINT-CLOUD
Country
France
Facility Name
Centre Catherine de Sienne
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54519
Country
France
Facility Name
Institut de Cancérologie de Lorraine
City
Vandoeuvre Les Nancy
ZIP/Postal Code
54519
Country
France
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31727113
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.
Results Reference
derived
Learn more about this trial
Validity of HER2-amplified Circulating Tumor Cells to Select Metastatic Breast Cancer Considered HER2-negative for Trastuzumab-emtansine (T-DM1) Treatment.
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