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CIrCuLAting Dna ESr1 Gene Mutations Analysis (CICLADES)

Primary Purpose

Breast Cancer

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
next-generation sequencing (NGS)
Sponsored by
Institut de Cancérologie de Lorraine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Breast Cancer focused on measuring Estrogen-receptor-positive breast cancer, aromatase inhibitor,, ESR1,, PIK3CA, AKT, endocrine resistance, circulating tumor DNA

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Female patient aged 18 and older
  2. Histologically confirmed estrogen-receptor-positive, HER2-negative breast cancer
  3. Proven metastatic (AJCC stage IV) or loco-regionally advanced (AJCC stage III) breast cancer, not amenable to surgery or radiation with curative intent.

  4. Indication to treat with first-line endocrine therapy for palliative care.

    • Patients already receiving first-line endocrine therapy can be enrolled up to 6 weeks after start of endocrine therapy.
    • Endocrine therapy can be prescribed in combination with a CDK4/6 inhibitor.
    • One prior regimen of chemotherapy for the treatment of advanced disease is allowed.
    • Prior (neo)adjuvant chemotherapy and/or (neo)adjuvant endocrine therapy is/are allowed; patients with recurrence while on adjuvant endocrine therapy can be enrolled.
  5. Patients who can benefit from an additional blood sample of 10ml. The total volume of each sample meets with the indications of the Order in force establishing the list of researches mentioned in 2 ° of Article L. 1121-1 of the Public Health Code.
  6. Informed consent explained to, understood by and signed by patient. Patient must be given a copy of informed consent.
  7. Patients affiliated to a social security scheme or benefit from a social regime

The prescription of medicinal product(s) is clearly separated from the decision to include the subject in this ISMRC.

Exclusion Criteria:

  1. Pregnant or breast-feeding woman.
  2. Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of advanced disease is allowed.
  3. Chemotherapy in combination with endocrine therapy.
  4. Targeted therapy, except CDK 4/6 inhibitor, in combination with endocrine therapy.
  5. Planned surgery or radiation with curative intent.
  6. Other active malignancy.
  7. Any concurrent severe and/or uncontrolled medical condition(s) which could compromise participation in the study.
  8. Patient whose general state and / or conditions do not permit the collection of the additional blood sample.
  9. Patients under guardianship, under curatorship or deprived of liberty.

Sites / Locations

  • Hôpital Claude Bernard
  • CHR Metz-Thionville
  • Centre d'oncologie Gentilly
  • Institut Jean Godinot
  • Polyclinique de Courlancy
  • Centre Henri Becquerel
  • Polyclinique de l'Orangerie
  • Clinique Saint Anne
  • CHU Strasbourg
  • Institut de cancérologie de Lorraine

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

experimental

Arm Description

Outcomes

Primary Outcome Measures

incidence of ESR1 mutations

Secondary Outcome Measures

incidence of PIK3CA and AKT1 mutations
prevalence of ESR1, PIK3CA and AKT1 mutations in patients with and without endocrine resistance at enrolment
prevalence of ESR1, PIK3CA and AKT1 mutations in patients according to mono vs combo therapy.
prevalence of mutations of other genes of interest included in the panel from the start of treatment to progression or end of follow-up
ESR1, PIK3CA and AKT1 mutations predictor of progression free survival

Full Information

First Posted
October 18, 2017
Last Updated
August 3, 2023
Sponsor
Institut de Cancérologie de Lorraine
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1. Study Identification

Unique Protocol Identification Number
NCT03318263
Brief Title
CIrCuLAting Dna ESr1 Gene Mutations Analysis
Acronym
CICLADES
Official Title
Monitoring of ESR1, PIK3CA and AKT ctDNA Mutations During Real-life Followup of Patients With Metastatic Breast Cancer Treated With Aromatase Inhibitors
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
December 7, 2017 (Actual)
Primary Completion Date
December 22, 2022 (Actual)
Study Completion Date
December 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut de Cancérologie de Lorraine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The estrogen-dependent nature of breast cancer was first reported in 1896 with the publication of George Beatson's observations on the regression of breast cancer following oophorectomy. Endocrine therapy, targeting ER either directly by selective estrogen receptor modulators (SERMs) and pure antagonists or indirectly by aromatase inhibitors (AIs) that block estrogen production, remains the mainstay of treatment of hormone-sensitive breast cancer in the adjuvant and metastatic settings. Intrinsic (de novo) and acquired endocrine resistance constitutes an important clinical challenge in the treatment of breast cancer and multiple mechanisms are suspected to underlie the emergence of endocrine resistance. The role of the estrogen receptor (ER), encoded by the ESR1 gene, in normal mammary gland development and the progression of breast cancer is well established. ESR1 mutations, occurring in 10 to 30% of ER-positive metastatic breast cancer resistant to AIs, lead to ligand-independent activation of the ER. For patients treated with AIs, monitoring of circulating tumour DNA (ctDNA) for ESR1, PIK3CA and AKT1 mutations could permit early detection of resistance to AIs as recently reported during 2016 American Society of Clinical Oncology (ASCO) meeting.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Estrogen-receptor-positive breast cancer, aromatase inhibitor,, ESR1,, PIK3CA, AKT, endocrine resistance, circulating tumor DNA

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
146 (Actual)

8. Arms, Groups, and Interventions

Arm Title
experimental
Arm Type
Other
Intervention Type
Diagnostic Test
Intervention Name(s)
next-generation sequencing (NGS)
Intervention Description
ESR1, PI3KCA and AKT extensive exon sequencing will be performed using NGS (Miseq Illumina) at the Biopathology department, Institut de Cancérologie de Lorraine (ISO15189 certified lab). Samples taken at baseline (t0), at progression (tp) and 3 months before progression (tp-3) will be systematically analyzed. The intermediate samples will be stored and kept for additional studies. Follow up assessment will be performed according to prescriber's directions.
Primary Outcome Measure Information:
Title
incidence of ESR1 mutations
Time Frame
1 day
Secondary Outcome Measure Information:
Title
incidence of PIK3CA and AKT1 mutations
Time Frame
1 day
Title
prevalence of ESR1, PIK3CA and AKT1 mutations in patients with and without endocrine resistance at enrolment
Time Frame
1 day
Title
prevalence of ESR1, PIK3CA and AKT1 mutations in patients according to mono vs combo therapy.
Time Frame
1 day
Title
prevalence of mutations of other genes of interest included in the panel from the start of treatment to progression or end of follow-up
Time Frame
1 day
Title
ESR1, PIK3CA and AKT1 mutations predictor of progression free survival
Time Frame
1 day

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Female patient aged 18 and older Histologically confirmed estrogen-receptor-positive, HER2-negative breast cancer Proven metastatic (AJCC stage IV) or loco-regionally advanced (AJCC stage III) breast cancer, not amenable to surgery or radiation with curative intent. Indication to treat with first-line endocrine therapy for palliative care. Patients already receiving first-line endocrine therapy can be enrolled up to 6 weeks after start of endocrine therapy. Endocrine therapy can be prescribed in combination with a CDK4/6 inhibitor. One prior regimen of chemotherapy for the treatment of advanced disease is allowed. Prior (neo)adjuvant chemotherapy and/or (neo)adjuvant endocrine therapy is/are allowed; patients with recurrence while on adjuvant endocrine therapy can be enrolled. Patients who can benefit from an additional blood sample of 10ml. The total volume of each sample meets with the indications of the Order in force establishing the list of researches mentioned in 2 ° of Article L. 1121-1 of the Public Health Code. Informed consent explained to, understood by and signed by patient. Patient must be given a copy of informed consent. Patients affiliated to a social security scheme or benefit from a social regime The prescription of medicinal product(s) is clearly separated from the decision to include the subject in this ISMRC. Exclusion Criteria: Pregnant or breast-feeding woman. Patient who received any prior systemic hormonal therapy for advanced breast cancer; no more than one prior regimen of chemotherapy for the treatment of advanced disease is allowed. Chemotherapy in combination with endocrine therapy. Targeted therapy, except CDK 4/6 inhibitor, in combination with endocrine therapy. Planned surgery or radiation with curative intent. Other active malignancy. Any concurrent severe and/or uncontrolled medical condition(s) which could compromise participation in the study. Patient whose general state and / or conditions do not permit the collection of the additional blood sample. Patients under guardianship, under curatorship or deprived of liberty.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MASSARD VINCENT, MD
Organizational Affiliation
Institut de Cancérologie de Lorraine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital Claude Bernard
City
Metz
ZIP/Postal Code
57070
Country
France
Facility Name
CHR Metz-Thionville
City
Metz
ZIP/Postal Code
57085
Country
France
Facility Name
Centre d'oncologie Gentilly
City
Nancy
Country
France
Facility Name
Institut Jean Godinot
City
Reims
ZIP/Postal Code
51100
Country
France
Facility Name
Polyclinique de Courlancy
City
Reims
ZIP/Postal Code
51100
Country
France
Facility Name
Centre Henri Becquerel
City
Rouen
ZIP/Postal Code
76038
Country
France
Facility Name
Polyclinique de l'Orangerie
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Facility Name
Clinique Saint Anne
City
Strasbourg
ZIP/Postal Code
67085
Country
France
Facility Name
CHU Strasbourg
City
Strasbourg
ZIP/Postal Code
67091
Country
France
Facility Name
Institut de cancérologie de Lorraine
City
Vandœuvre-lès-Nancy
ZIP/Postal Code
54509
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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CIrCuLAting Dna ESr1 Gene Mutations Analysis

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