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Completed

NCT Number: NCT03318263

CIrCuLAting Dna ESr1 Gene Mutations Analysis

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.

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Key information

Conditions

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

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

CHR Metz-Thionville, Metz, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Primary outcomes

  1. incidence of ESR1 mutations

    Time frame: 1 day

Secondary outcomes

  1. incidence of PIK3CA and AKT1 mutations

    Time frame: 1 day

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

    Time frame: 1 day

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

    Time frame: 1 day

  4. 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

  5. ESR1, PIK3CA and AKT1 mutations predictor of progression free survival

    Time frame: 1 day

Sponsors and collaborators

Lead sponsor

Institut de Cancérologie de Lorraine

Other

Registry information

Official study title

Monitoring of ESR1, PIK3CA and AKT ctDNA Mutations During Real-life Followup of Patients With Metastatic Breast Cancer Treated With Aromatase Inhibitors

Acronym: CICLADES

Important dates

Study start
2017
Primary completion
2022
Study completion
2022
First posted
Oct 23, 2017
Registry last updated
Aug 4, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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