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Исследование по оценке эффективности и безопасности алпелисиба плюс фулвестрант у участников с HR-положительным (HR+), HER2-отрицательным распространенным раком молочной железы после лечения ингибитором CDK4/6 и ингибитором ароматазы. (EPIK-B5)

28 сентября 2026 г. обновлено: Novartis Pharmaceuticals

EPIK-B5: Рандомизированное, двойное слепое, плацебо-контролируемое исследование фазы III алпелисиба в комбинации с фулвестрантом у мужчин и женщин в постменопаузе с HR-положительным, HER2-отрицательным распространенным раком молочной железы с мутацией PIK3CA, у которых прогрессировало во время или после Ингибитор ароматазы и ингибитор CDK4/6

The purpose of this study is to complement Study CBYL719C2301 (SOLAR-1) and obtain more comprehensive data on the efficacy and safety of alpelisib (BYL719) in combination with fulvestrant compared with placebo plus fulvestrant in men or postmenopausal women with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation who progressed or relapsed on or after treatment with an AI plus a CDK4/6 inhibitor.

Обзор исследования

Статус

Активный, не рекрутирующий

Условия

Вмешательство/лечение

Подробное описание

This is a Phase III, randomized, double-blind, placebo-controlled, international, multi-center trial. Men and postmenopausal women will be randomized to either alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant. Randomization will follow a 1:1 randomization ratio and be stratified by presence of lung and/or liver metastases (yes vs. no) and setting at last prior CDK4/6 inhibitor therapy (adjuvant vs metastatic).

Study treatment with alpelisib plus fulvestrant or alpelisib-matching placebo plus fulvestrant will be initiated on Cycle 1 Day 1, and will continue until disease progression per RECIST v1.1 as per BIRC assessment, start of new antineoplastic therapy, death, lost to follow-up, or withdrawal of consent. A cycle is defined as 28 days.

Тип исследования

Интервенционный

Регистрация (Действительный)

210

Фаза

  • Фаза 3

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Места учебы

  • Бельгия
      • Brussels, Бельгия, 1200
        • Novartis Investigative Site
      • Brussels, Бельгия, 1000
        • Novartis Investigative Site
      • Ghent, Бельгия, 9000
        • Novartis Investigative Site
      • Leuven, Бельгия, 3000
        • Novartis Investigative Site
      • Liège, Бельгия, 4000
        • Novartis Investigative Site
    • Oost Vlaanderen
      • Sint-Niklaas, Oost Vlaanderen, Бельгия, 9100
        • Novartis Investigative Site
  • Болгария
      • Plovdiv, Болгария, 4004
        • Novartis Investigative Site
      • Sofia, Болгария, 1330
        • Novartis Investigative Site
  • Венгрия
      • Budapest, Венгрия, 1122
        • Novartis Investigative Site
  • Германия
      • Augsburg, Германия, 86150
        • Novartis Investigative Site
      • Berlin, Германия, 13353
        • Novartis Investigative Site
      • Essen, Германия, 45136
        • Novartis Investigative Site
      • Lübeck, Германия, 23538
        • Novartis Investigative Site
    • North Rhine-Westphalia
      • Cologne, North Rhine-Westphalia, Германия, 50937
        • Novartis Investigative Site
  • Греция
      • Athens, Греция, 115 22
        • Novartis Investigative Site
      • Pátrai, Греция, 265 04
        • Novartis Investigative Site
  • Дания
      • Aalborg, Дания, 9000
        • Novartis Investigative Site
  • Ирландия
      • Dublin, Ирландия, D04 T6F4
        • Novartis Investigative Site
  • Испания
      • A Coruña, Испания, 15009
        • Novartis Investigative Site
      • Barcelona, Испания, 08036
        • Novartis Investigative Site
      • Madrid, Испания, 28040
        • Novartis Investigative Site
      • Málaga, Испания, 29011
        • Novartis Investigative Site
      • Zaragoza, Испания, 50009
        • Novartis Investigative Site
    • Extremadura
      • Badajoz, Extremadura, Испания, 06080
        • Novartis Investigative Site
    • Madrid
      • Pozuelo de Alarcón, Madrid, Испания, 28223
        • Novartis Investigative Site
    • Principality of Asturias
      • Oviedo, Principality of Asturias, Испания, 33011
        • Novartis Investigative Site
  • Италия
      • Naples, Италия, 80131
        • Novartis Investigative Site
    • BA
      • Bari, BA, Италия, 70124
        • Novartis Investigative Site
    • BG
      • Bergamo, BG, Италия, 24127
        • Novartis Investigative Site
    • BO
      • Bologna, BO, Италия, 40138
        • Novartis Investigative Site
    • FI
      • Florence, FI, Италия, 50134
        • Novartis Investigative Site
    • GE
      • Genova, GE, Италия, 16132
        • Novartis Investigative Site
    • MI
      • Milan, MI, Италия, 20133
        • Novartis Investigative Site
      • Milan, MI, Италия, 20141
        • Novartis Investigative Site
      • Milan, MI, Италия, 20132
        • Novartis Investigative Site
      • Rozzano, MI, Италия, 20089
        • Novartis Investigative Site
    • PA
      • Palermo, PA, Италия, 90127
        • Novartis Investigative Site
    • PD
      • Padova, PD, Италия, 35128
        • Novartis Investigative Site
    • PN
      • Aviano, PN, Италия, 33081
        • Novartis Investigative Site
    • RM
      • Roma, RM, Италия, 00168
        • Novartis Investigative Site
    • TR
      • Terni, TR, Италия, 05100
        • Novartis Investigative Site
  • Канада
    • Alberta
      • Calgary, Alberta, Канада, T2N 5G2
        • Novartis Investigative Site
    • Ontario
      • Ottawa, Ontario, Канада, K1H 8L6
        • Novartis Investigative Site
  • Польша
      • Bydgoszcz, Польша, 85-796
        • Novartis Investigative Site
  • Португалия
      • Coimbra, Португалия, 3000-075
        • Novartis Investigative Site
      • Lisbon, Португалия, 1400-038
        • Novartis Investigative Site
      • Lisbon, Португалия, 1099-023
        • Novartis Investigative Site
      • Porto, Португалия, 4200-072
        • Novartis Investigative Site
  • Румыния
    • Cluj
      • Floreşti, Cluj, Румыния, 407280
        • Novartis Investigative Site
  • Словакия
      • Bratislava, Словакия, 812 50
        • Novartis Investigative Site
      • Bratislava, Словакия, 833 10
        • Novartis Investigative Site
      • Košice, Словакия, 041 91
        • Novartis Investigative Site
  • Финляндия
      • Helsinki, Финляндия, 00029
        • Novartis Investigative Site
      • Tampere, Финляндия, 33521
        • Novartis Investigative Site
  • Франция
      • Besançon, Франция, 25030
        • Novartis Investigative Site
      • Clermont-Ferrand, Франция, 63011
        • Novartis Investigative Site
      • La Roche-sur-Yon, Франция, 85925
        • Novartis Investigative Site
      • Lyon, Франция, 69373
        • Novartis Investigative Site
      • Marseille, Франция, 13273
        • Novartis Investigative Site
      • Montpellier, Франция, 34298
        • Novartis Investigative Site
      • Paris, Франция, 75970
        • Novartis Investigative Site
      • Paris, Франция, 75475
        • Novartis Investigative Site
      • Valenciennes, Франция, 59300
        • Novartis Investigative Site
  • Чехия
      • Brno, Чехия, 656 53
        • Novartis Investigative Site
      • Nový Jičín, Чехия, 741 01
        • Novartis Investigative Site
      • Prague, Чехия, 128 08
        • Novartis Investigative Site
      • Prague, Чехия, 100 34
        • Novartis Investigative Site
      • Prague, Чехия, 140 59
        • Novartis Investigative Site

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

От 18 лет до 100 лет (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

Key Inclusion Criteria:

  • Participant is an adult ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines.
  • Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory.
  • Participant has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situ hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is required by local laboratory testing.
  • Participant has at least one measurable lesion as per RECIST v1.1 criteria as assessed by Investigator (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation).
  • Participant has recurrence or progression of disease during or after combined AI (i.e. letrozole, anastrozole, exemestane) and CDK4/6 inhibitor therapy. The combined AI and CDK4/6 inhibitor therapy does not need to be the latest treatment regimen (including adjuvant setting).
  • Participant has received ≤ 2 prior lines of systemic therapies overall in the metastatic setting, of which a maximum of 1 line of prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy) is permitted.
  • The presence of PIK3CA mutation(s) determined in tumor tissue prior to enrollment either by a Novartis designated laboratory or in tumor tissue or plasma ctDNA by a local laboratory using a Food and Drug Administration (FDA)-approved PIK3CA Companion Diagnostics (CDx) test for alpelisib or the CE-IVD QIAGEN Therascreen® PIK3CA RGQ PCR test.
  • If female, then the participant must be in postmenopausal status.

Key Exclusion Criteria:

  • Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy (ET) per the Investigator's best judgment.
  • Participant who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine/endocrine-based therapy with no treatment for metastatic disease.
  • Participant has received prior treatment with fulvestrant, any oral selective estrogen receptor degrader (SERD), any Phosphatidylinositol-3-Kinase (PI3K), mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor.

Other Inclusion and Exclusion Criteria do apply

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Назначение кроссовера
  • Маскировка: Тройной

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: Alpelisib plus fulvestrant

Alpelisib 300 mg orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15, and on Day 1 on every Cycle thereafter, in a 28 days cycle.
Лекарство: Alpelisib

Alpelisib (tablets) administered at 300mg orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

Лекарство: Fulvestrant

Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 and then at Day 1 of each subsequent cycle (each cycle is 28 days).
Плацебо Компаратор: Alpelisib-matching placebo plus fulvestrant

Alpelisib-matching placebo orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15 and on Day 1 on every Cycle thereafter, in a 28 days cycle.

After Protocol Amendment 5 is implemented, alpelisib matching-placebo will no longer be supplied or administered once participants have been unblinded.
Лекарство: Fulvestrant

Fulvestrant (prefilled syringe) 500mg administered intramuscularly at Cycle 1 Day 1 and 15 and then at Day 1 of each subsequent cycle (each cycle is 28 days).

Лекарство: Alpelisib-matching placebo

Alpelisib-matching placebo (tablets) administered orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

After Protocol Amendment 5 is implemented, alpelisib matching-placebo will no longer be supplied or administered once participants have been unblinded.

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria
Временное ограничение: From randomization to date of the first documented progression or death due to any cause, assessed up to a maximum duration of 60 months.

Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed by the Blinded Independent Review Committee (BIRC) according to RECIST 1.1.
From randomization to date of the first documented progression or death due to any cause, assessed up to a maximum duration of 60 months.

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Overall survival (OS)
Временное ограничение: From the date of randomization to the date of death up to a maximum duration of 60 months

Overall survival (OS) is defined as the time from randomization to the date of death due to any cause
From the date of randomization to the date of death up to a maximum duration of 60 months
Overall response rate (ORR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
Временное ограничение: From the date of randomization up to a maximum duration of 60 months

Overall response rate (ORR) with confirmed response is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR), as per BIRC and according to RECIST 1.1
From the date of randomization up to a maximum duration of 60 months
Clinical benefit rate (CBR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
Временное ограничение: From the date of randomization up to a maximum duration of 60 months

Clinical benefit rate (CBR) with confirmed response is defined as the proportion of participants with a best overall response of confirmed CR or PR, or SD lasting for a duration of at least 24 weeks. CR, PR and SD are defined as per BIRC review according to RECIST 1.1
From the date of randomization up to a maximum duration of 60 months
Duration of response (DOR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria
Временное ограничение: From first documented response to the date of first progression or deaths, up to a maximum duration of 60 months

Duration of response (DOR) with confirmed response only applies to participants whose best overall response is confirmed complete response (CR) or confirmed partial response (PR) according to RECIST 1.1 based on tumor response data per BIRC review. The start date is the date of first documented response of CR or PR and the end date is defined as the date of the first documented progression or death due to underlying cancer.
From first documented response to the date of first progression or deaths, up to a maximum duration of 60 months
Time to response (TTR) based on BIRC assessments and using RECIST v1.1 criteria
Временное ограничение: From the date of randomization to the first documented response up to a maximum duration of 60 months

Time to response (TTR) is defined as the time from the date of randomization to the first documented response of either complete response (CR) or partial response (PR), which must be subsequently confirmed. CR and PR are based on tumor response data as per BIRC review and according to RECIST 1.1
From the date of randomization to the first documented response up to a maximum duration of 60 months
PFS based on BIRC assessment and using RECIST v1.1 criteria for participants by PIK3CA mutation status
Временное ограничение: From the date of randomization up to a maximum duration of 60 months

Progression-free survival (PFS) is defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed by the Blinded Independent Review Committee (BIRC) according to RECIST 1.1. Results will be presented by PIK3CA mutation status measured in circulating tumor deoxyribonucleic acid (ctDNA) collected at baseline.
From the date of randomization up to a maximum duration of 60 months
Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline
Временное ограничение: From the date of randomization up to maximum duration of 60 months

Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status (PS) from baseline is defined as the time from the date of randomization to the date when ECOG PS has definitively worsened by at least one category compared to baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG PS back to the baseline category or better.
From the date of randomization up to maximum duration of 60 months
Time to definitive (10%) deterioration in the global health status/Quality of Life (QoL) and symptom scale scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core Module (EORTC QLQ-C30)
Временное ограничение: From the date of randomization up to maximum duration of 60 months

Time to definitive (10%) deterioration in global health status/Quality of Life (QoL) and symptom scale scores of the EORTC QLQ-C30 is defined as the time from the date of randomization to the date of the first occurrence of at least a 10% worsening from baseline in the global health status/QoL or symptom scale scores, with no subsequent improvement above this threshold during treatment or until death from any cause. The EORTC QLQ-C30 is a validated questionnaire assessing cancer patients' quality of life over the past week, comprising 30 items across 5 functional scales, 3 symptom scales, 6 single items, and a global health status/QoL scale. Scores range from 0 to 100, with higher scores indicating a higher response level.
From the date of randomization up to maximum duration of 60 months
Change from baseline in global health status/QoL and symptom scale scores of the EORTC QLQ-C30
Временное ограничение: From the date of randomization up to maximum duration of 60 months

Change from baseline in global health status/Quality of Life (QoL) and symptom scale scores of the EORTC QLQ-C30 refers to the variation in scores from baseline across domain scores, health states, overall health status, and index values at each assessment timepoint. The EORTC QLQ-C30 is a validated questionnaire designed to assess the quality of life of cancer patients over the past week. It includes 30 items comprising 5 functional scales, 3 symptom scales, 6 single items, and a global health status/QoL scale. Each scale and item is scored from 0 to 100, with higher scores indicating a higher response level.
From the date of randomization up to maximum duration of 60 months
Time from randomization to objective tumour progression on next line treatment or death from any cause (PFS2)
Временное ограничение: From the date of randomization up to maximum duration of 60 months

Time from randomization to objective tumor progression on next-line treatment or death from any cause (PFS2) is defined as the time from the date of randomization to the earliest occurrence of either documented disease progression on next-line therapy, as assessed by the investigator, or death from any cause.
From the date of randomization up to maximum duration of 60 months

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Novartis Pharmaceuticals

Следователи

  • Директор по исследованиям: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Действительный)

17 декабря 2021 г.

Первичное завершение (Оцененный)

28 января 2027 г.

Завершение исследования (Оцененный)

26 февраля 2027 г.

Даты регистрации исследования

Первый отправленный

1 сентября 2021 г.

Впервые представлено, что соответствует критериям контроля качества

1 сентября 2021 г.

Первый опубликованный (Действительный)

9 сентября 2021 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

29 сентября 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

28 сентября 2026 г.

Последняя проверка

1 сентября 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • CBYL719C2303
  • 2023-509133-39-00 (Идентификатор реестра: CTIS (EU))
  • 2023 (Грант/контракт NIH США)

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

ДА

Описание плана IPD

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Нет

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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