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CIrCuLAting Dna ESr1 Gene Mutations Analysis (CICLADES)

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ClinicalTrials.gov Identifier: NCT03318263
Recruitment Status : Recruiting
First Posted : October 23, 2017
Last Update Posted : August 8, 2018
Sponsor:
Information provided by (Responsible Party):
Institut de Cancérologie de Lorraine

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.


Condition or disease Intervention/treatment Phase
Breast Cancer Diagnostic Test: next-generation sequencing (NGS) Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 146 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Monitoring of ESR1, PIK3CA and AKT ctDNA Mutations During Real-life Followup of Patients With Metastatic Breast Cancer Treated With Aromatase Inhibitors
Actual Study Start Date : December 7, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : June 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
experimental Diagnostic Test: next-generation sequencing (NGS)
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 Measures :
  1. incidence of ESR1 mutations [ Time Frame: 1 day ]

Secondary Outcome Measures :
  1. incidence of PIK3CA and AKT1 mutations [ Time Frame: 1 day ]
  2. predictors of progression free survival [ Time Frame: 1 day ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female patients aged 18 or older
  • Histologically confirmed estrogen-receptor-positive, HER2-negative breast cancer
  • Previously untreated metastatic (AJCC stage IV) or locoregionally advanced inoperable (AJCC stage III) breast cancer
  • Indication to treat with AIs
  • Exclusive endocrine monotherapy
  • Informed consent explained to, understood by and signed by patient. Patient given copy of informed consent

Exclusion Criteria:

  • Tumour tissue sample not available for pathological review or correlative studies
  • Chemotherapy or endocrine therapy for breast cancer within the last 12 months before inclusion
  • Any concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study
  • Pregnant or breast feeding women

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03318263


Contacts
Contact: MERLIN JEAN LOUIS 00 33 3 83 59 83 07 jl.merlin@nancy.unicancer.fr
Contact: TOSTI PRISCILLIA, PhD 00 33 3 83 59 86 57 p.tosti@nancy.unicancer.fr

Locations
France
Hôpital Claude Bernard Recruiting
Metz, France, 57070
Contact: GARDNER Miriam, MD         
CHR Metz-Thionville Recruiting
Metz, France, 57085
Contact: LONGO Rafaelle, MD         
Centre d'oncologie Gentilly Recruiting
Nancy, France
Contact: Célia BECUWE, MD         
Institut Jean Godinot Recruiting
Reims, France, 51100
Contact: SAVOYE Aude-Marie, MD         
Polyclinique de Courlancy Recruiting
Reims, France, 51100
Contact: PRULHIERE Karine, MD         
Centre Henri Becquerel Recruiting
Rouen, France, 76038
Contact: Florian CLATOT, MD         
Polyclinique de l'Orangerie Not yet recruiting
Strasbourg, France, 67000
Contact: ACHILLE Mihaela, MD         
Clinique Saint Anne Recruiting
Strasbourg, France, 67085
Contact: TAZI Youssef, MD         
CHU Strasbourg Recruiting
Strasbourg, France, 67091
Contact: BARHELEMY Philippe, MD         
Institut de cancérologie de Lorraine Recruiting
Vandœuvre-lès-Nancy, France, 54509
Contact: MASSARD VINCENT, MD       v.massard@nancy.unicancer.fr   
Sponsors and Collaborators
Institut de Cancérologie de Lorraine
Investigators
Principal Investigator: MASSARD VINCENT, MD Institut de Cancérologie de Lorraine

Responsible Party: Institut de Cancérologie de Lorraine
ClinicalTrials.gov Identifier: NCT03318263     History of Changes
Other Study ID Numbers: 2017-A01767-46
First Posted: October 23, 2017    Key Record Dates
Last Update Posted: August 8, 2018
Last Verified: August 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Institut de Cancérologie de Lorraine:
Estrogen-receptor-positive breast cancer
aromatase inhibitor,
ESR1,
PIK3CA
AKT
endocrine resistance
circulating tumor DNA

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs