SHIELD: Surveillance of HR+/HER2- : Implementing ESR1m Long-term Monitoring and Detection in 1L aBC (SHIELD)
A Multicenter Study to Describe the Frequency and Emergence of ESR1 Mutations in Patients With Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer Receiving First-Line Endocrine Based Therapy
This is a multicountry, multicenter, observational study in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer receiving first-line endocrine-based therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor. The study aims to describe the prevalence of ESR1 mutations at baseline and the emergence of ESR1 mutations over time using circulating tumor DNA testing in routine clinical practice.
Patients receiving first-line treatment for at least 6 months and no more than 18 months, without evidence of disease progression at study entry, may undergo baseline ESR1 mutation testing. Patients with a negative baseline result may undergo longitudinal monitoring approximately every 3 months, for up to 18 months or 6 testing timepoints, to assess emergence of ESR1 mutations. The study will also describe mutation subtypes, testing methods used in routine practice, selected clinical characteristics, and treatment patterns across participating countries.
Обзор исследования
Статус
Вмешательство/лечение
Подробное описание
This is a multicountry, multicenter, observational study designed to determine the prevalence of ESR1 mutations at baseline and to assess the emergence of ESR1 mutations during longitudinal surveillance in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (HR+/HER2- aBC) receiving first-line treatment with an aromatase inhibitor (AI) in combination with a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.
Eligible patients are adults with histologically or cytologically confirmed HR+/HER2- advanced breast cancer who have been receiving first-line AI plus CDK4/6 inhibitor therapy for at least 6 months and no more than 18 months, without evidence of disease progression according to investigator assessment, and who are willing and able to provide blood samples for circulating tumor DNA (ctDNA) testing at predefined intervals.
Following informed consent, baseline data will be collected in electronic case report forms and will include sociodemographic characteristics, clinical and tumor history, testing methods, and treatment patterns. A baseline blood sample will be collected for ctDNA-based ESR1 mutation testing using testing methods applied in routine clinical practice, including but not limited to quantitative polymerase chain reaction (qPCR), digital polymerase chain reaction (dPCR), and next-generation sequencing (NGS), according to local availability and site capability. Testing will be performed in validated laboratories in accordance with local standard operating procedures.
Patients who are negative for ESR1 mutation at baseline will undergo longitudinal ctDNA monitoring approximately every 12 weeks (+/-4 weeks), for up to 18 months or 6 testing time points from initial testing, whichever occurs first. Patients who test positive for ESR1 mutation at baseline or during follow-up will discontinue further study surveillance and will continue to receive routine clinical care as determined by the treating physician. The date of first ESR1 mutation detection will be recorded.
The primary objectives are to determine the prevalence of ESR1 mutations at baseline and the emergence rate and time to emergence of ESR1 mutations during the surveillance period among patients who are ESR1 negative at initial testing. Secondary objectives include assessment of ESR1 mutation frequency by duration of first-line therapy and by testing method, distribution of specific ESR1 mutation subtypes, co-mutations with other clinically relevant biomarkers when available, patient clinical and sociodemographic characteristics, testing and treatment patterns, and associations between ESR1 mutation status and relevant patient or treatment factors.
Approximately 3,000 patients are planned to be enrolled at about 30 sites in 15 countries across Asia, Latin America, and the Middle East and Africa. The estimated recruitment period is 12 months.
Тип исследования
Регистрация (Оцененный)
Контакты и местонахождение
Контакты исследования
- Имя: AstraZeneca Clinical Study Information Center
- Номер телефона: +1877240-9479
- Электронная почта: information.center@astrazeneca.com
Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Метод выборки
Исследуемая популяция
Описание
Inclusion Criteria:
- Age 18 years or older at the time of informed consent and willing and able to provide informed consent before any study-related procedures.
- Histologically- or cytologically-confirmed hormone receptor-positive (ER- and/or progesterone receptor-positive), human epidermal growth factor receptor 2-negative (HER2-negative) advanced breast cancer.
- Receiving first-line therapy with an aromatase inhibitor in combination with a CDK4/6 inhibitor for at least 6 months and no more than 18 months, with no evidence of disease progression at study entry, as assessed by the investigator.
- Able and willing to provide a blood sample for circulating tumour DNA testing for ESR1 mutation assessment at approximately quarterly intervals.
Exclusion Criteria:
- Evidence of disease progression during first-line aromatase inhibitor plus CDK4/6 inhibitor therapy, based on investigator assessment.
- Known ESR1 mutation status at study entry.
Учебный план
Как устроено исследование?
Детали дизайна
Когорты и вмешательства
Группа / когорта |
Вмешательство/лечение |
|---|---|
|
Participants with HR-positive, HER2-negative advanced breast cancer
Adults with HR-positive, HER2-negative advanced breast cancer receiving first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor for 6 to 18 months without disease progression at study entry.
Participants undergo baseline ESR1 mutation testing using circulating tumour DNA; those with a negative baseline result may undergo follow-up testing approximately every 3 months for up to 18 months.
|
Blood sampling for ctDNA-based ESR1 mutation testing, which are associated with minimal additional risk and burden compared with routine clinical practice
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Prevalence of ESR1 mutations in circulating tumour DNA
Временное ограничение: At baseline, approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
Number and proportion of patients with at least one ESR1 mutation
|
At baseline, approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
|
Emergence of ESR1 mutations during longitudinal ctDNA surveillance
Временное ограничение: At approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
Number and proportion of patients who are detected with ESR1 mutation
|
At approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
|
Time to first detection of an ESR1 mutation
Временное ограничение: From first-line AI plus CDK4/6 inhibitor initiation to first ESR1 mutation detection
|
Time in months from initiation of first-line treatment with AI and CDK4/6 inhibitors to first detection of ESR1mutation
|
From first-line AI plus CDK4/6 inhibitor initiation to first ESR1 mutation detection
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Prevalence of ESR1 mutations by duration of ongoing first-line AI plus CDK4/6 inhibitor therapy
Временное ограничение: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
Number and proportion of participants with ESR1 mutations by duration of ongoing first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor
|
At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
|
Frequency of ESR1 mutation-positive results by testing method
Временное ограничение: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
Number and proportion of participants with ESR1 mutation-positive results according to the circulating tumour DNA testing method used.
|
At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
|
Distribution of ESR1 mutation subtypes and allele frequency
Временное ограничение: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
Number and proportion of participants with specific ESR1 mutation subtypes detected by circulating tumour DNA testing.
|
At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
|
Frequency of additional co-mutations among ESR1 mutation-positive participants
Временное ограничение: At baseline and approximately every 3 months through study completion, up to approximately 18 months after initial ESR1 testing
|
Number and proportion of participants with ESR1 mutations who have at least 1 additional clinically relevant co-mutation detected, where available.
|
At baseline and approximately every 3 months through study completion, up to approximately 18 months after initial ESR1 testing
|
|
Baseline and follow-up characteristics of the study population
Временное ограничение: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
Summary of selected sociodemographic, clinical, tumour, and testing characteristics of the study population.
|
At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
|
Relationship between ESR1 mutation status and selected participant and treatment characteristics
Временное ограничение: At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
Assessment of the relationship between ESR1 mutation status and selected participant, disease, testing, and treatment characteristics.
|
At baseline and at approximately 3, 6, 9, 12, 15, and 18 months after initial testing
|
|
Treatment patterns for advanced breast cancer
Временное ограничение: From enrolment through study completion, up to approximately 18 months after initial ESR1 testing
|
Summary of first-line treatment regimens for advanced breast cancer, including endocrine therapy and CDK4/6 inhibitor use, and duration of therapy.
|
From enrolment through study completion, up to approximately 18 months after initial ESR1 testing
|
|
Prior treatment patterns for early-stage breast cancer
Временное ограничение: At baseline
|
Summary of prior therapies received for early-stage breast cancer in participants who later developed advanced breast cancer, including duration of therapy and reasons for discontinuation, where available.
|
At baseline
|
Соавторы и исследователи
Спонсор
Соавторы
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
Другие идентификационные номера исследования
- D9673L00023
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
Описание плана IPD
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared
Сроки обмена IPD
Критерии совместного доступа к IPD
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.
Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
Совместное использование IPD Поддерживающий тип информации
- STUDY_PROTOCOL
- САП
Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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