CIrCuLAting Dna ESr1 Gene Mutations Analysis

NCT03318263 | Completed

• 1 other identifier: 2017-A01767-46
• Study Type: interventional
• Target: 146
• Locations: 1 country
• Sites: 10

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.

Conditions

Breast Cancer

Keywords

Estrogen-receptor-positive breast cancer; aromatase inhibitor,; ESR1,; PIK3CA; AKT; endocrine resistance; circulating tumor DNA

Outcome Measures

Primary Outcomes (1)

• incidence of ESR1 mutations

  1 day

Secondary Outcomes (5)

• incidence of PIK3CA and AKT1 mutations

  1 day

• prevalence of ESR1, PIK3CA and AKT1 mutations in patients with and without endocrine resistance at enrolment

  1 day

• prevalence of ESR1, PIK3CA and AKT1 mutations in patients according to mono vs combo therapy.

  1 day

• prevalence of mutations of other genes of interest included in the panel from the start of treatment to progression or end of follow-up

  1 day

• ESR1, PIK3CA and AKT1 mutations predictor of progression free survival

  1 day

Study Arms (1)

experimental

OTHER

Diagnostic Test: next-generation sequencing (NGS)

Interventions

next-generation sequencing (NGS) DIAGNOSTIC_TEST

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.

experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Cancérologie de Lorraine: lead

Study Sites (10)

Hôpital Claude Bernard

Metz, 57070, France

Location

CHR Metz-Thionville

Metz, 57085, France

Location

Centre d'oncologie Gentilly

Nancy, France

Location

Institut Jean Godinot

Reims, 51100, France

Location

Polyclinique de Courlancy

Reims, 51100, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

Polyclinique de l'Orangerie

Strasbourg, 67000, France

Location

Clinique Saint Anne

Strasbourg, 67085, France

Location

CHU Strasbourg

Strasbourg, 67091, France

Location

Institut de cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54509, France

Location

MeSH Terms

Conditions

Breast Neoplasms; Hereditary Sensory and Autonomic Neuropathies

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Officials

• MASSARD VINCENT, MD

  Institut de Cancérologie de Lorraine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2017
• First Posted: October 23, 2017
• Study Start: December 7, 2017
• Primary Completion: December 22, 2022
• Study Completion: December 22, 2022
• Last Updated: August 4, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (10)