CIrCuLAting Dna ESr1 Gene Mutations Analysis

NCT ID: NCT03318263

Last Updated: 2023-08-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-12-07
• Study Completion Date: 2022-12-22

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

experimental

Group Type: OTHER

next-generation sequencing (NGS)

Intervention Type: 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.

Interventions

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.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Institut de Cancérologie de Lorraine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MASSARD VINCENT, MD

Role: PRINCIPAL_INVESTIGATOR

Institut de Cancérologie de Lorraine

Locations

Hôpital Claude Bernard

Metz, , France

CHR Metz-Thionville

Metz, , France

Centre d'oncologie Gentilly

Nancy, , France

Institut Jean Godinot

Reims, , France

Polyclinique de Courlancy

Reims, , France

Centre Henri Becquerel

Rouen, , France

Polyclinique de l'Orangerie

Strasbourg, , France

Clinique Saint Anne

Strasbourg, , France

CHU Strasbourg

Strasbourg, , France

Institut de cancérologie de Lorraine

Vandœuvre-lès-Nancy, , France

Countries

France

Other Identifiers

2017-A01767-46

Identifier Type: -

Identifier Source: org_study_id