Исследование по оценке комбинации энкорафениба и цетуксимаба по сравнению с иринотеканом/цетуксимабом или инфузионным введением 5-фторурацила (5-ФУ)/фолиевой кислоты (ФК)/иринотекана (FOLFIRI)/цетуксимаба у китайских пациентов с метастатическим колоректальным раком с мутацией BRAF V600E. (NAUTICALCRC)
8 апреля 2026 г. обновлено: Pierre Fabre Medicament
Многоцентровое, рандомизированное, открытое, 2-групповое исследование фазы II с вводной фазой по оценке безопасности комбинации энкорафениба и цетуксимаба по сравнению с иринотеканом/цетуксимабом или инфузионным введением 5-фторурацила (5-ФУ)/фолиевой кислоты (ФК) /Иринотекан (FOLFIRI)/Цетуксимаб у китайских пациентов с метастатическим колоректальным раком с мутацией BRAF V600E.
В настоящее время разрабатывается энкорафениб (с биниметинибом или без него) в комбинации с цетуксимабом для лечения взрослых пациентов с метастатическим колоректальным раком (мКРР) с протоонкогеном B-RAF, мутацией серин/треонинкиназы V600E (BRAF V600E), у которых ранее получали системную терапию.
Обзор исследования
Статус
Завершенный
Вмешательство/лечение
Тип исследования
Интервенционный
Регистрация (Действительный)
107
Фаза
- Фаза 2
Контакты и местонахождение
В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.
Места учебы
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Beijing Municipality
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Beijing, Beijing Municipality, Китай, 100730
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
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Beijing, Beijing Municipality, Китай, 100036
- Beijing Cancer Hospital
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Fujian
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Fuzhou, Fujian, Китай, 350014
- Fujian Medical University - Fujian Provincial Cancer Hospital
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Xiamen, Fujian, Китай, 361001
- The First Affiliated Hospital of Xiamen University
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Guangdong
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Foshan, Guangdong, Китай, 528010
- The First People's Hospital of Foshan
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Guangzhou, Guangdong, Китай, 510095
- Cancer Center of Guangzhou Medical University
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Guangzhou, Guangdong, Китай, 510655
- The Sixth Affiliated Hospital Sun Yat-sen University
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Shantou, Guangdong, Китай, 515041
- Cancer Hospital Affiliated to Shantou University Medical College
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Shenzhen, Guangdong, Китай, 518036
- Peking University Shenzhen Hospital
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Hebei
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Baoding, Hebei, Китай, 071000
- The Affiliated Hospital of Hebei University
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Heilongjiang
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Harbin, Heilongjiang, Китай, 150040
- Harbin Medical University Cancer Hospital
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Henan
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Zhengzhou, Henan, Китай, 450052
- The First Affiliated Hospital of Zhengzhou University
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Zhengzhou, Henan, Китай, 450008
- Henan Cancer Hospital
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Hubei
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Wuhan, Hubei, Китай, 430071
- Zhongnan Hospital of Wuhan University
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Wuhan, Hubei, Китай, 430022
- Union Hospital Tongji Medical College Huazhong University Of Science And Technology
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Wuhan, Hubei, Китай, 430030
- Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
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Hunan
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Changsha, Hunan, Китай, 410008
- Xiangya Hospital Central South University
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Jiangsu
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Changzhou, Jiangsu, Китай, 213003
- The First People's Hospital of Changzhou
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Jiangxi
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Ganzhou, Jiangxi, Китай, 341001
- First Affiliated Hospital of Gannan Medical University
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Nanchang, Jiangxi, Китай, 330006
- The First Affiliated Hospital of Nanchang University
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Nanchang, Jiangxi, Китай, 330006
- The Second Affiliated Hospital of Nanchang University
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Jilin
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Changchun, Jilin, Китай, 130021
- The First Hospital of Jilin University
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Liaoning
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Jinzhou, Liaoning, Китай, 121011
- The First Affiliated Hospital of Jinzhou Medical University
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Shenyang, Liaoning, Китай, 110001
- The First Hospital of China Medical University
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Shenyang, Liaoning, Китай, 110042
- Liaoning Cancer Hospital & Institute
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Shaanxi
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Xi'an, Shaanxi, Китай, 710068
- Shaanxi Provincial People's Hospital
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Китай, 200032
- Zhongshan Hospital Fudan University
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Shanghai, Shanghai Municipality, Китай, 200040
- Huashan Hospital Fudan University
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Shanghai, Shanghai Municipality, Китай, 200092
- Xinhua Hospital Affilliated to Shanghai Jiaotong University School of Medicine
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Shanghai, Shanghai Municipality, Китай, 200120
- Shanghai East Hospital, Tongji University
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Sichuan
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Neijiang, Sichuan, Китай, 641000
- The Second People's Hospital of Neijiang
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Tianjin Municipality
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Tianjin, Tianjin Municipality, Китай, 300060
- Tianjin Medical University Cancer Institute and Hospital
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Zhejiang
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Hangzhou, Zhejiang, Китай, 310003
- The First Affiliated Hospital - Zhejiang University School of Medicine
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Hangzhou, Zhejiang, Китай, 310016
- Sir Run Run Shaw Hospital - Zhejiang University School of Medicine
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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
18 лет и старше (Взрослый, Пожилой взрослый)
Принимает здоровых добровольцев
Нет
Описание
Критерии включения для молекулярного предварительного скрининга:
Для того чтобы участник имел право пройти предварительный скрининг молекулярной опухоли, должны быть соблюдены следующие критерии включения:
- Китайский участник мужского или женского пола в возрасте ≥18 лет на момент получения информированного согласия.
- Гистологически или цитологически подтвержденный метастатический колоректальный рак (КРР).
- Имеет право на получение цетуксимаба в соответствии с утвержденной в Китае инструкцией в отношении статуса мутации вирусного онкогенного гомолога саркомы крыс (RAS) опухоли (т.е. одобрен для статуса гомолога вирусного онкогена крысиной саркомы дикого типа (RAS wt)).
- Способен предоставить достаточное количество репрезентативных образцов опухоли для централизованного проспективного лабораторного тестирования протоонкогена B-RAF, статуса мутации серин/треонинкиназы (BRAF), а также ретроспективного статуса RAS wt и тестирования микросателлитной нестабильности (MSI).
Критерии включения для периода лечения:
Чтобы участник имел право на участие в этом исследовании, он должен соответствовать следующим критериям включения:
- Китайский участник мужского или женского пола в возрасте ≥18 лет на момент информированного согласия.
- Гистологически или цитологически подтвержденный CRC, который является метастатическим и нерезектабельным на момент включения в исследование (т. не подходит для полной хирургической резекции при скрининге).
- Наличие мутации BRAF V600E в опухолевой ткани, предварительно установленной с помощью локального анализа в любое время до скрининга или в центральной лаборатории.
ПРИМЕЧАНИЕ. Могут применяться другие критерии включения, определенные протоколом.
Критерии исключения для молекулярного предварительного скрининга:
Участники, отвечающие любому из следующих критериев, не имеют права на предварительный скрининг молекулярной опухоли:
- Предшествующее лечение рецепторами эпидермального фактора роста (анти-EGFR)
- Более двух предшествующих режимов лечения при метастатическом поражении.
- Известные противопоказания для приема цетуксимаба или иринотекана в запланированной дозе в соответствии с самой последней местной инструкцией по применению цетуксимаба и иринотекана.
- Известная история синдрома Жильбера или наличие любого из следующих генотипов: уридин-5'-дифосфоглюкуронозилтрансферазы (UGT) 1A1*6/*6, UGT1A1*28/*28 или UGT1A1*6/*28.
- Лептоменингиальная болезнь.
Критерии исключения для периода лечения:
- Предварительное лечение любым ингибитором протоонкогена серин/треонин-протеинкиназы (RAF), цетуксимабом, панитумумабом или другими ингибиторами EGFR.
- Симптоматическое метастазирование в головной мозг.
- Лептоменингиальная болезнь.
- Использование любых растительных лекарств/добавок или любых лекарств или продуктов питания, которые являются умеренными или сильными ингибиторами или индукторами цитохрома P450 (CYP)3A4/5 ≤1 недели до начала исследовательского вмешательства.
- Известный анамнез острого или хронического панкреатита в течение 6 месяцев до начала исследуемого вмешательства.
ПРИМЕЧАНИЕ. Могут применяться другие определенные протоколом критерии исключения.
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: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Экспериментальный: Энкорафениб и цетуксимаб
Этап ввода в эксплуатацию (SLI): 28-дневные циклы энкорафениба один раз в день (QD) 300 мг (4 капсулы для приема внутрь по 75 мг) и цетуксимаба 400 мг/м² начальная доза (120-минутная инфузия), затем 250 мг/м² (60-минутная инфузия) после этого один раз в неделю Рандомизированная (фаза II) фаза: 28-дневные циклы энкорафениба один раз в день (QD) 300 мг (4 капсулы для приема внутрь по 75 мг) и цетуксимаба 400 мг/м² начальная доза (120-минутная инфузия), затем 250 мг/м² (60-минутная инфузия) после этого один раз в неделю |
оральная твердая капсула
Другие имена:
внутривенное вливание
Другие имена:
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Экспериментальный: Иринотекан и цетуксимаб или FOLFIRI и цетуксимаб
Рандомизированная (фаза II) фаза: либо иринотекан и цетуксимаб, либо FOLFIRI и цетуксимаб в 28-дневных циклах. Иринотекан и цетуксимаб:
ИЛИ ЖЕ FOLFIRI и цетуксимаб:
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оральная твердая капсула
Другие имена:
внутривенное вливание
Другие имена:
Комбинация: иринотекан (также известный как камптозар, камптотецин-11 и СРТ-11) внутривенное вливание, фолиновая кислота (также известная как 5-формилтетрагидрофолиевая кислота и лейковорин) внутривенное вливание и 5-ФУ (также известный как фторурацил) внутривенное болюсное введение /внутривенная инфузия
Другие имена:
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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Safety Lead-in Phase (SLI): Incidence of Dose Limiting Toxicities (DLTs)
Временное ограничение: Cycle 1 (up to 28 days)
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DLT rate was estimated based on data from DLT-evaluable participants during the DLT-evaluation period (which is the first 28 days after the first dose of study intervention in the SLI) to assess the safety and tolerability of the doublet arm.
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Cycle 1 (up to 28 days)
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Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Primary Completion Date
Временное ограничение: From first dose to the earliest documented progression or death due to any cause, with a minimal participant's follow-up of 36 weeks and a maximum treatment exposure of 68 weeks
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PFS was defined as the time from the date of randomization to the earliest documented disease progression (PD) as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause.
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From first dose to the earliest documented progression or death due to any cause, with a minimal participant's follow-up of 36 weeks and a maximum treatment exposure of 68 weeks
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Randomized Phase 2: Progression-free Survival (PFS) by Blinded (to Treatment Received) Independent Central Review (BICR) at the Final Analysis
Временное ограничение: From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
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PFS was defined as the time from the date of randomization to the earliest documented disease progression as determined by BICR assessment per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or death due to any cause.
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From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per BICR
Временное ограничение: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
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cORR as determined by Blinded (to treatment received) Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Confirmed Objective Response Rate (cORR) Per Investigator
Временное ограничение: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
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cORR as determined by investigator assessment per RECIST version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
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Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Duration of Response (DOR) Per BICR
Временное ограничение: From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by BICR per RECIST Version 1.1, or death due to any cause.
PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
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From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Duration of Response (DOR) Per Investigator
Временное ограничение: From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by investigator assessment per RECIST Version 1.1, or death due to any cause.
PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
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From time of response to the earliest documented PD or death due to underlying disease, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Overall Duration of Exposure to Study Treatment
Временное ограничение: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Exposure to the study intervention was defined as the time interval between the actual date of first study intervention administration (included) and the actual date of last study intervention administration (included), i.e., as the quantity "date of last study intervention administration date of first study intervention administration + 1 day".
Duration of exposure by treatment arm was computed as the maximum of all durations of exposure for each drug of the assigned regimen.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Временное ограничение: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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A TEAE is any untoward medical occurrence in a participant temporally associated with the use of study drug, whether or not considered related to the study drug.
Number of participants reporting TEAEs were reported in this outcome measure.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Serious TEAEs
Временное ограничение: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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A serious TEAE is a TEAE that results in significant health consequences, such as death, hospitalization, or permanent disability.
Number of participants reporting serious TEAEs were reported in this outcome measure.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Incidence of Dose Interruptions, Dose Modifications and Discontinuations Due to Adverse Events (AEs)
Временное ограничение: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 68 weeks
|
An AE is any untoward medical occurrence in a participant, whether or not considered related to the study intervention.
Number of participants with dose interruptions, dose modifications and dose discontinuations due to AEs were reported in this outcome measure.
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Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 68 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Vital Sign Abnormalities
Временное ограничение: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Clinically notable changes were defined as participants meeting the elevated or low values criterion compared to baseline.
The criterion for clinically notable elevated values included: systolic blood pressure (BP): ≥ 160 millimeters of mercury (mmHg) and an increase ≥ 20 mmHg from baseline; diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; weight (kg) increase from baseline of ≥ 10 percent; body temperature [degree Celsius (deg C)] ≥ 37.5 deg C. The criterion for clinically notable low values included: systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; weight: ≥ 20 percent decrease from baseline; body temperature [deg C]: ≤ 36 °C.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values
Временное ограничение: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Clinically notable ECG changes were defined as participants meeting the criterion for QT interval, QT interval corrected for heart rate using Fridericia's formula (QTcF), and heart rate compared to baseline.
The criterion for QT interval and QTcF included: increase from baseline > 30 msec (ms); increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms.
The criterion for heart rate included: increase from baseline > 25 percent to a value > 100 beats per minute (bpm), decrease from baseline > 25 percent and to a value < 50 bpm.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters
Временное ограничение: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Clinically notable shift was defined as a worsening from baseline by at least 2 Grades, or to Grade 3 or above based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03.
'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease.
'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase.
Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters
Временное ограничение: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
|
Clinically notable shift was defined as a worsening from baseline by at least 2 Grades, or to Grade 3 or above based on NCI-CTCAE version 4.03.
'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease.
'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase.
Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
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Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 111 weeks
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Safety Lead-in Phase: Number of Participants With Notable Dermatological Abnormalities
Временное ограничение: From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 111 weeks
|
Dermatological examination was performed to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and primary melanoma, as these have been reported to occur with selective B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor treatment.
[1] The category "Other" includes all other dermatological findings identified during examination (e.g.
rash acneiform, skin hyperpigmentation...).
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From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 111 weeks
|
|
Safety Lead-in Phase: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale
Временное ограничение: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 68 weeks
|
The performance status of participants was assessed using the Eastern Co-operative Oncology Group (ECOG) scale.
The scale was defined with the range from 0 to 5 with lower score mean a lower functional impairment, and a higher score (e.g. 5) corresponding to death.
|
Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 68 weeks
|
|
Safety Lead-in Phase: Evaluation of the Plasma Concentrations of Encorafenib
Временное ограничение: First day of treatment (Cycle 1 Day I) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day I) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Safety Lead-in Phase: Evaluation of the Serum Concentrations of Cetuximab
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Safety Lead-in Phase: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Safety Lead-in Phase: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Safety Lead-in Phase: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Progression-free Survival (PFS) by Investigator
Временное ограничение: From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
PFS was defined as the time from the date of randomization to the earliest documented date of PD as determined by investigator assessment per RECIST Version 1.1, or death due to any cause.
PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
|
From first dose to the earliest documented PD or death due to any cause, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Confirmed Objective Response Rate (cORR) in ENCO + CETUX Arm vs Control Arm Per BICR
Временное ограничение: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
cORR as determined by Blinded (to treatment received) Independent Central Review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Confirmed Objective Response Rate (cORR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Временное ограничение: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
cORR as determined by investigator assessment per RECIST Version 1.1, was defined as the proportion of participants with a best overall response of either complete response (CR) or partial response (PR), where CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Duration of Response (DOR) in ENCO + CETUX Arm vs Control Arm Per BICR
Временное ограничение: From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by BICR per RECIST Version 1.1, or death due to any cause.
PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
|
From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Duration of Response (DOR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Временное ограничение: From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
DOR was defined for confirmed responders (CR or PR) only, as the time from the date of the first documented response to the earliest date of disease progression (PD) as determined by investigator assessment per RECIST Version 1.1, or death due to any cause.
PD: at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions were evaluated.
|
From time of response to the earliest documented PD or death due to underlying disease, with a minimal participant's follow-up of 19 months and a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Confirmed Disease Control Rate (cDCR) in ENCO + CETUX Arm vs Control Arm Per BICR
Временное ограничение: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
cDCR was defined as the proportion of participants with a confirmed Best Overall Response (BOR) of CR, PR or Stable Disease (SD), as determined by BICR per RECIST Version 1.1.
CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
|
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Confirmed Disease Control Rate (cDCR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Временное ограничение: Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
cDCR was defined as the proportion of participants with a confirmed Best Overall Response (BOR) of CR, PR or Stable Disease (SD), as determined by investigator assesment per RECIST Version 1.1.
CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
|
Every 6 weeks (± 7 days) from first dose for the first 24 week, then every 12 weeks (± 7 days) until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Time to Response (TTR) in ENCO + CETUX Arm vs Control Arm Per BICR
Временное ограничение: From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
|
TTR for confirmed responses was defined for responders (CR or PR) as the time between the date of randomization until the first documented response of CR or PR as determined by BICR per RECIST Version 1.1.
CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Time to Response (TTR) in ENCO + CETUX Arm vs Control Arm Per Investigator
Временное ограничение: From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
|
TTR for confirmed responses was defined for responders (CR or PR) as the time between the date of randomization until the first documented response of CR or PR as determined by investigator assessment per RECIST Version 1.1.
CR: disappearance of all target and and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm, and PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
|
From day 1 until first documented response, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Overall Survival (OS)
Временное ограничение: From randomization to death due to any cause, with a maximum treatment exposure of 116 weeks
|
OS was defined as time from randomization until date of death due to any cause.
|
From randomization to death due to any cause, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Overall Duration of Exposure to Study Treatment
Временное ограничение: Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 116 weeks
|
Exposure to the study intervention was defined as the time interval between the actual date of first study intervention administration (included) and the actual date of last study intervention administration (included), i.e., as the quantity "date of last study intervention administration date of first study intervention administration + 1 day".
Duration of exposure by treatment arm was computed as the maximum of all durations of exposure for each drug of the assigned regimen.
|
Day 1 until 30 days after study intervention discontinuation, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Временное ограничение: Day 1 until 30 days after study intervention discontinuation
|
A TEAE is any untoward medical occurrence in a participant temporally associated with the use of study drug, whether or not considered related to the study drug.
Number of participants reporting TEAEs were reported in this outcome measure.
|
Day 1 until 30 days after study intervention discontinuation
|
|
Randomized Phase 2: Number of Participants With Serious TEAEs
Временное ограничение: Day 1 until 30 days after study intervention discontinuation
|
A serious TEAE is a TEAE that results in significant health consequences, such as death, hospitalization, or permanent disability.
Number of participants reporting serious TEAEs were reported in this outcome measure.
|
Day 1 until 30 days after study intervention discontinuation
|
|
Randomized Phase 2: Number of Participants With Clinically Notable Vital Sign Abnormalities
Временное ограничение: Day 1 until 30 days after last dose of study treatment
|
Clinically notable changes were defined as participants meeting the elevated or low values criterion compared to baseline.
The criterion for clinically notable elevated values included: systolic blood pressure (BP): ≥ 160 millimeters of mercury (mmHg) and an increase ≥ 20 mmHg from baseline; diastolic BP: ≥ 100 mmHg and an increase ≥ 15 mmHg from baseline; heart rate : ≥ 120 beats/min (bpm) with increase from baseline of ≥ 15 bpm; weight (kg) increase from baseline of ≥ 10 percent; body temperature [degree Celsius (deg C)] ≥ 37.5 deg C. The criterion for clinically notable low values included: systolic BP: ≤ 90 mmHg with decrease from baseline of ≥ 20 mmHg; diastolic BP: ≤ 50 mmHg with decrease from baseline of ≥ 15 mmHg; heart rate: ≤ 50 bpm with decrease from baseline of ≥ 15 bpm; weight: ≥ 20 percent decrease from baseline; body temperature [deg C]: ≤ 36 °C.
|
Day 1 until 30 days after last dose of study treatment
|
|
Randomized Phase 2: Number of Participants With Clinically Notable Electrocardiogram (ECG) Values
Временное ограничение: Day 1 until 30 days after last dose of study treatment
|
Clinically notable ECG changes were defined as participants meeting the criterion for QT interval, QT interval corrected for heart rate using Fridericia's formula (QTcF), and heart rate compared to baseline.
The criterion for QT interval and QTcF included: increase from baseline > 30 msec (ms); increase from baseline > 60 ms, new > 450 ms, new > 480 ms, new > 500 ms.
The criterion for heart rate included: increase from baseline > 25 percent to a value > 100 beats per minute (bpm), decrease from baseline > 25 percent and to a value < 50 bpm.
|
Day 1 until 30 days after last dose of study treatment
|
|
Randomized Phase 2: Number of Participants With Clinically Notable Shifts in Hematology and Coagulation Laboratory Parameters
Временное ограничение: Day 1 until 30 days after last dose of study treatment
|
Clinically notable shift was defined as a worsening from baseline by at least 2 grades, or to grade 3 or above based on NCI-CTCAE version 4.03.
'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease.
'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase.
Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
|
Day 1 until 30 days after last dose of study treatment
|
|
Randomized Phase 2: Number of Participants With Clinically Notable Shifts in Serum Chemistry Laboratory Parameters
Временное ограничение: Day 1 until 30 days after last dose of study treatment
|
Clinically notable shift was defined as a worsening from baseline by at least 2 grades, or to grade 3 or above based on NCI-CTCAE version 4.03.
'Low' laboratory parameter thresholds are defined as values falling below the institutional Lower Limit of Normal (LLN) that meet the criteria for a Grade 1 or a higher decrease.
'High' laboratory parameter thresholds are defined as values exceeding the institutional Upper Limit of Normal (ULN) that meet the criteria for a Grade 1 or higher increase.
Where, Grade 1: mild, asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated; Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of hospitalization indicated; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death.
|
Day 1 until 30 days after last dose of study treatment
|
|
Randomized Phase 2: Number of Participants With Notable Dermatological Abnormalities
Временное ограничение: From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 116 weeks
|
Dermatological examination was performed to monitor for the possible development of keratoacanthoma and/or squamous cell carcinoma and primary melanoma, as these have been reported to occur with selective B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor treatment.
[1] All other dermatological findings identified during examination (e.g.
rash acneiform, skin hyperpigmentation...).
|
From screening and every 8 weeks from Cycle 1 Day 1 (i.e. on Day 1 of Cycles 1, 3, 5, 7…), the end of treatment visit and the 30-day safety follow up visit, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Measurement of Performance Status Using the Eastern Co-operative Oncology Group (ECOG) Scale
Временное ограничение: Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 116 weeks
|
The performance status of participants was assessed using the Eastern Co-operative Oncology Group (ECOG) scale.
The scale was defined with the range from 0 to 5 with lower score mean a lower functional impairment, and a higher score (e.g. 5) corresponding to death.
[1] Participants with no assessment of ECOG in the time frame.
|
Day 1 until 30 days after last dose of study treatment, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Time to Definitive Deterioration in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) Questionnaire Scores
Временное ограничение: Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer Patients (EORTC QLQ-C30) questionnaire consisted of nine multi-item scales: five functional scales (physical, role, cognitive, emotional and social); three symptom scales (fatigue, pain, nausea and vomiting); and a global health and Quality of Life (QoL) scale.
Each scale in the questionnaire was scored (0 to 100).
High scores represented a high health/quality of life.
Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms.
|
Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Time to Definitive Deterioration in the European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Questionnaire
Временное ограничение: Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
The European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) consisted of the EQ-5D descriptive system and the EQ visual analogue scale (VAS).
The descriptive system consisted of five dimension (mobility, self-care, usual activities, pain/discomfort and anxiety/depression), each was rated according to a five-point verbal rating scale (VRS): 1. no problems, 2. slight problems, 3. moderate problems, 4. severe problems and 5. extreme problems) and translated into a five-digit number that described the participant's health state.
Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms.
|
Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Time to Definitive Deterioration in the Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) Questionnaire
Временное ограничение: Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
The Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) was a validated quality of life questionnaire for patient reported outcome assessment.
The Functional Assessment of Cancer Therapy-Colon Cancer (FACT-C) consisted of 36 items, presented on a five-point Likert scale, in four domains of well-being (physical, emotional, social and functional) and the Colorectal Cancer Subscale.
Higher score reflects a better quality of life.
Time to definitive deterioration (at least 10% worsening relative to Baseline with no later improvement) was assessed for both randomized phase treatment arms.
|
Day 1 until 30 days safety follow-up, with a maximum treatment exposure of 116 weeks
|
|
Randomized Phase 2: Evolution in the Patient Global Impression of Change (PGIC) Questionnaire
Временное ограничение: Cycle 2 Day 1 until 30 days safety follow-up
|
The Patient Global Impression of Change (PGIC) questionnaire is a scale often used to anchor and characterize participant reported outcome (PRO) findings.
This consisted of questions that asked participants to evaluate their colorectal cancer symptoms since starting study intervention according to a seven-point verbal rating scale: 1. very much improved, 2. much improved, 3. minimally improved, 4. no change, 5. minimally worse, 6. much worse, 7. very much worse.
Completions of questionnaire are summarized per treatment group and study visits.
Number of participants analyzed correspond to the actual number of participants who completed the questionnaire at the corresponding visit.
|
Cycle 2 Day 1 until 30 days safety follow-up
|
|
Randomized Phase 2: Evaluation of the Plasma Concentrations of Encorafenib
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Serum Concentrations of Cetuximab
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Area Under the Curve (AUC) Derived From Plasma Concentration of Encorafenib
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Area Under the Curve (AUC) Derived From Serum Concentration of Cetuximab
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Minimum Concentration (Cmin) Derived From Plasma Concentration of Encorafenib
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Minimum Concentration (Cmin) Derived From Serum Concentration of Cetuximab
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Maximum Concentration (Cmax) Derived From Plasma Concentration of Encorafenib
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of encorafenib.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
|
Randomized Phase 2: Evaluation of the Maximum Concentration (Cmax) Derived From Serum Concentration of Cetuximab
Временное ограничение: First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of cetuximab.
|
First day of treatment (Cycle 1 Day 1) and at steady state after 1 month treatment (Cycle 2 Day 1). Each cycle of 28 days.
|
Другие показатели результатов
Мера результата |
Временное ограничение |
|---|---|
|
Рандомизированная фаза 2: изменения по сравнению с исходным уровнем карциноэмбрионального антигена (СЕА) и ракового антигена 19-9 (СА19-9) в начале каждого цикла и в конце лечения.
Временное ограничение: Скрининг (день от -28 до -1) до завершения исследования, примерно от 12 до 29 месяцев.
|
Скрининг (день от -28 до -1) до завершения исследования, примерно от 12 до 29 месяцев.
|
|
Рандомизированная фаза 2: статус микросателлитной нестабильности (MSI) в образцах, фиксированных формалином и залитых парафином (FFPE), с использованием установленного анализа полимеразной цепной реакции (ПЦР) в образце опухоли по сравнению с контролем зародышевой линии при скрининге.
Временное ограничение: Скрининг (День -28 до День -1)
|
Скрининг (День -28 до День -1)
|
Соавторы и исследователи
Здесь вы найдете людей и организации, участвующие в этом исследовании.
Спонсор
Соавторы
Следователи
- Главный следователь: Shen Lin, MD, Peking University Cancer Hospital & Institute
Публикации и полезные ссылки
Лицо, ответственное за внесение сведений об исследовании, добровольно предоставляет эти публикации. Это может быть что угодно, связанное с исследованием.
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)
14 сентября 2021 г.
Первичное завершение (Действительный)
19 декабря 2023 г.
Завершение исследования (Действительный)
7 декабря 2024 г.
Даты регистрации исследования
Первый отправленный
30 апреля 2021 г.
Впервые представлено, что соответствует критериям контроля качества
5 августа 2021 г.
Первый опубликованный (Действительный)
13 августа 2021 г.
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
30 апреля 2026 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
8 апреля 2026 г.
Последняя проверка
1 февраля 2026 г.
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Новообразования по локализации
- Новообразования
- Кишечные заболевания
- Желудочно-кишечные новообразования
- Новообразования пищеварительной системы
- Заболевания пищеварительной системы
- Желудочно-кишечные заболевания
- Новообразования кишечника
- Заболевания прямой кишки
- Заболевания толстой кишки
- Колоректальные новообразования
- Аминокислоты, пептиды и белки
- Белки
- Гетероциклические соединения, 1-кольцо
- Гетероциклические соединения
- Гетероциклические соединения, 2-кольцо
- Гетероциклические соединения, слитое кольцо
- Камптотекин
- Алкалоиды
- Ферменты и коэнзименты
- Антитела, моноклональные, гуманизированные
- Антитела, моноклональные
- Антитела
- Иммуноглобулины
- Иммунопротеины
- Белки крови
- Сывороточные глобулины
- Глобулины
- Пиримидины
- Формилтетрагидрофолаты
- Тетрагидрофолаты
- Фолиевая кислота
- Птерины
- Птеридины
- Урацил
- Пиримидиноны
- Коэнзименты
- Иринотекан
- Цетуксимаб
- Фторурацил
- Лейковорин
- Энорафениб
- Протокол IFL
Другие идентификационные номера исследования
- W00090GE202
Планирование данных отдельных участников (IPD)
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НЕТ
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
продукт, произведенный в США и экспортированный из 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. .