Study Of Lapatinib In Combination With Paclitaxel In The Treatment Of Newly Diagnosed Inflammatory Breast Cancer
27 мая 2017 г. обновлено: GlaxoSmithKline
A Phase II Study to Evaluate the Efficacy, Safety, and Pharmacodynamics of Lapatinib in Combination With Paclitaxel as Neoadjuvant Therapy in Patients With Newly Diagnosed Inflammatory Breast Cancer
This Study was designed to determine how effective and safe a new investigational drug, lapatinib, is in combination with paclitaxel in treating patients with newly diagnosed inflammatory breast cancer.
Tumor tissue collected pre-treatment, following 14 days of treatment and at the time of surgical resection will be examined for pathologic response and biologic activity by IHC (immunohistochemistry) within the tumor.
Treatment will consist of 14 days of lapatinib monotherapy followed by 12 weeks of combination therapy with lapatinib and paclitaxel.
Blood samples for hematology and chemistry panels, MUGA/ECHO exams and physical exams will be performed throughout the study to monitor safety.
Обзор исследования
Статус
Завершенный
Условия
Вмешательство/лечение
Тип исследования
Интервенционный
Регистрация (Действительный)
49
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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New South Wales
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Campbelltown, New South Wales, Австралия, 2560
- GSK Investigational Site
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Liverpool, New South Wales, Австралия, 2170
- GSK Investigational Site
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Randwick, New South Wales, Австралия, 2031
- GSK Investigational Site
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Queensland
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South Brisbane, Queensland, Австралия, 4101
- GSK Investigational Site
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South Australia
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Bedford Park, South Australia, Австралия, 5042
- GSK Investigational Site
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Victoria
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Box Hill, Victoria, Австралия, 3128
- GSK Investigational Site
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Ringwood East, Victoria, Австралия, 3128
- GSK Investigational Site
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Ramat Gan, Израиль, 52621
- GSK Investigational Site
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Barcelona, Испания, 08035
- GSK Investigational Site
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Girona, Испания, 17007
- GSK Investigational Site
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Valencia, Испания, 46010
- GSK Investigational Site
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Ontario
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Toronto, Ontario, Канада, M4N 3M5
- GSK Investigational Site
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Auckland, Новая Зеландия
- GSK Investigational Site
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London, Соединенное Королевство, SW3 6JJ
- GSK Investigational Site
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Florida
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Miami, Florida, Соединенные Штаты, 33136
- GSK Investigational Site
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Illinois
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Chicago, Illinois, Соединенные Штаты, 60637
- GSK Investigational Site
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Zion, Illinois, Соединенные Штаты, 60099
- GSK Investigational Site
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Texas
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Houston, Texas, Соединенные Штаты, 77030
- GSK Investigational Site
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Sfax, Тунис, 3000
- GSK Investigational Site
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Sfax, Тунис, 3029
- GSK Investigational Site
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Tunis, Тунис, 1007
- GSK Investigational Site
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Tunis, Тунис, 1004
- GSK Investigational Site
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Bayonne, Франция, 64100
- GSK Investigational Site
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Lille Cedex, Франция, 59020
- GSK Investigational Site
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Paris cedex 13, Франция, 75651
- GSK Investigational Site
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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
Полы, имеющие право на обучение
Все
Описание
Inclusion criteria:
- Tumor accessible for multiple biopsies
- ECOG (Eastern Cooperative Oncology Group) performance status 0-2
- Adequate bone marrow
- Renal and hepatic function
- LVEF (left ventricular ejection fraction) greater than 0% based on ECHO (echocardiogram) or MUGA (multigated acquisition).
Exclusion criteria:
- Females who are pregnant or nursing.
- Any unstable, pre-existing major medical condition.
- Received an investigational drug within the past 4 weeks.
- Had major surgery in the past 2 weeks.
- Currently receiving amiodarone or has received amiodarone in the past 6 months.
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: Нерандомизированный
- Интервенционная модель: Параллельное назначение
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Экспериментальный: Overall study
A Single arm study with 2 cohorts of participants.
Cohort A consists of participants with tumors overexpressing HER2 and/or EGFR.
Cohort B consists of participants with tumors expressing EGFR without overexpressing HER2.
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Daily-monotherapy [1500 milligrams (mg)] for 14 days, then daily combination therapy (with weekly paclitaxel) for 12 weeks
Weekly (80mg/m^2) combination therapy (with daily Lapatinib) for 12 weeks
Другие имена:
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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Percentage of participants with pathologic complete response rate (pCR)
Временное ограничение: Week 12
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pCR was defined as the percentage of participants who achieved an assessment of complete response (CR) following pathologic review of resected tissue.
CR was the disappearance of all target lesions.
Participants in each cohort with unknown or missing response (i.e., those that did not undergo surgery) were included in the denominator when calculating the percentage.
From an efficacy standpoint, the HER2+ population response was considered to be of special interest.
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Week 12
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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Percentage of participants with pCR that underwent surgical resection
Временное ограничение: Week 12
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pCR for participants that underwent surgical (surg) resection was defined as the percentage of participants within each cohort who achieved an assessment of CR following pathologic review of resected tissue.
CR was the disappearance of all target lesions.
Participants in each cohort that did not undergo surgical resection were excluded from the denominator when calculating the percentage.
From an efficacy standpoint, the HER2+ population response was considered to be of special interest.
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Week 12
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Percentage of participants with objective response rate (ORR) at the end of study (Response evaluation criteria in solid tumor [RECIST])
Временное ограничение: Week 14
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ORR at the end of the study was defined as the number of participants within each cohort who had a confirmed CR or partial response (PR) at the end of the study divided by the total number of participants enrolled in each cohort.
CR was the disappearance of all target lesions.
PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter.
Each participant's response was based on the investigator assessment of best response using RECIST criteria.
Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage.
From an efficacy standpoint, the HER2+ population was considered to be of special interest.
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Week 14
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Percentage of participants with ORR at the end of study (Clinically Evaluable Skin Disease Criteria)
Временное ограничение: Week 14
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ORR at the end of the study was defined as the number of participants within each cohort who had a confirmed CR or PR at the end of the study divided by the total number of participants enrolled in each cohort.
CR was the disappearance of all target lesions.
PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter.
Each participant's response was based on the investigator assessment of best response using Clinically Evaluable Skin Disease Criteria.
Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage.
From an efficacy standpoint, HER2+ population was considered to be of special interest.
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Week 14
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Percentage of participants with ORR at the end of study ('Best' of RECIST and Clinically Evaluable Skin Disease Criteria)
Временное ограничение: Week 14
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ORR at the end of the study was defined as the number of participants within each cohort who had a confirmed CR or PR at the end of the study divided by the total number of participants enrolled in each cohort.
CR was the disappearance of all target lesions.
PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter.
The best response of the participant was defined by the 'Best' combined response (RECIST and Clinically Evaluable Skin Disease Criteria) provided there is no evidence of disease progression.
Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage.
From an efficacy standpoint, the HER2+ population was considered to be special interest.
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Week 14
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Percentage of participants with investigator-Assessed Best Response at the end of monotherapy phase (Day 14) (Clinically Evaluable Skin Disease Criteria)
Временное ограничение: Day 14
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ORR at the end of the monotherapy phase was defined as the percentage of participants within each cohort who had a confirmed CR or PR at the end of lapatinib monotherapy (Day 14) divided by the total number of participants enrolled in each cohort.
CR was the disappearance of all target lesions.
PR was at least a 30 percent decrease in the sum of the longest diameter of target lesions, taking as a reference, the Baseline sum longest diameter.
Each participant's response was based on the investigator assessment of best response using clinically evaluable skin disease criteria.
Participants in each cohort with unknown or missing response was treated as non-responders; i.e. they were included in the denominator when calculating the percentage.
From an efficacy standpoint, the HER2+ population was considered to be special interest.
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Day 14
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Number of participants with adverse events (AEs) and serious adverse events (SAEs)
Временное ограничение: Up to Week 14, surgical resection and post treatment
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An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
An SAE was defined as any untoward medical occurrence that, at any dose that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect, resulted in deterioration in left ventricular cardiac function and caused Grade 3 or 4 interstitial pneumonitis.
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Up to Week 14, surgical resection and post treatment
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Number of participants with shift from Baseline in hematological toxicity grade
Временное ограничение: Day 14 and up to Week 23, surg resection and post treatment
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Hematology was summarized for hemoglobin (Hb), platelets, white blood cell count (WBC), neutrophils (Neu), lymphocytes by scheduled assessment and also according to the maximum common terminology criteria (CTC) toxicity grade.
Baseline was the most recent lab value prior to and within two weeks of the first dose of lapatinib.
Change from Baseline was calculated as the value at each visit minus Baseline value.
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Day 14 and up to Week 23, surg resection and post treatment
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Number of participants with shift from Baseline in clinical chemistry toxicity grade
Временное ограничение: Day 14, Week 4, 8, 12, 16, 20, Surg resection and post treatment
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Clinical chemistry was summarized for sodium, potassium (K), bicarbonate (bicarb), albumin (alb), calcium, gamma glutamyl transferase (GGT), creatinine (creat), total bilirubin (TB), alkaline phosphatase (ALP), aspartate amino transferase (AST) and alanine amino transferase (ALT) by scheduled assessment and also according to the maximum CTC toxicity grade.
Baseline was the most recent lab value prior to and within two weeks of the first dose of lapatinib.
Change from Baseline was calculated as the value at each visit minus Baseline value.
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Day 14, Week 4, 8, 12, 16, 20, Surg resection and post treatment
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Change from Baseline in vital signs- Systolic blood pressure (SBP) and Diastolic blood pressure (DBP)
Временное ограничение: Day 14, Week 1 and up to Week 24, surg resection and post treatment
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Vitals signs (SBP and DBP) were assessed from screening until the post treatment phase.
Baseline was the most recent blood pressure (BP) mean prior to the first dose of lapatinib.
Change from Baseline was calculated as the mean at each visit minus the mean at Baseline.
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Day 14, Week 1 and up to Week 24, surg resection and post treatment
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Change from Baseline in vital signs- Heart Rate (HR)
Временное ограничение: Day 14, Week 1 and up to Week 24, surg resection and post treatment
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Vitals signs (HR) were assessed from screening until the post treatment phase.
Baseline was the most recent BP mean prior to the first dose of lapatinib.
Change from Baseline was calculated as the mean at each visit minus the mean at Baseline.
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Day 14, Week 1 and up to Week 24, surg resection and post treatment
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Change from Baseline in vital signs- Body temperature
Временное ограничение: Day 14, Week 1 and up to Week 24, surg resection and post treatment
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Vitals signs (body temperature) were assessed from screening until the post treatment phase.
Baseline was the most recent BP mean prior to the first dose of lapatinib.
Change from Baseline was calculated as the mean at each visit minus the mean at Baseline.
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Day 14, Week 1 and up to Week 24, surg resection and post treatment
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Number of participants with abnormal electrocardiogram (ECG) findings
Временное ограничение: Screening and unscheduled
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ECG was performed at screening and at unscheduled visits.
Participants with abnormal clinically significant and abnormal not clinically significant ECG findings was reported.
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Screening and unscheduled
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Number of participants with change from Baseline in echocardiogram (ECHO) or Multi-gated angiogram (MUGA) results at any post Baseline visit
Временное ограничение: Screening, Week 8, 16, 24, post treatment
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For ECHO and MUGA scans, the left ventricular ejection fraction (percent) was summarized for each scheduled assessment.
Absolute change from Baseline was summarized according to the following categories: any increase, 0 to less than 20 percent decrease, >=20 percent decrease or >=20 percent decrease and below the lower limit of normal (LLN).
Baseline was the most recent ECOG evaluation prior to the first dose of lapatinib.
Change from Baseline was calculated as the value at the post treatment minus Baseline value.
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Screening, Week 8, 16, 24, post treatment
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Соавторы и исследователи
Здесь вы найдете людей и организации, участвующие в этом исследовании.
Спонсор
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)
11 апреля 2005 г.
Первичное завершение (Действительный)
1 ноября 2006 г.
Завершение исследования (Действительный)
1 ноября 2006 г.
Даты регистрации исследования
Первый отправленный
25 мая 2005 г.
Впервые представлено, что соответствует критериям контроля качества
25 мая 2005 г.
Первый опубликованный (Оценивать)
26 мая 2005 г.
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
31 мая 2017 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
27 мая 2017 г.
Последняя проверка
1 мая 2017 г.
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Кожные заболевания
- Новообразования
- Новообразования по локализации
- Заболевания груди
- Новообразования молочной железы
- Воспалительные новообразования молочной железы
- Молекулярные механизмы фармакологического действия
- Ингибиторы ферментов
- Противоопухолевые агенты
- Модуляторы тубулина
- Антимитотические агенты
- Модуляторы митоза
- Противоопухолевые агенты растительного происхождения
- Ингибиторы протеинкиназы
- Паклитаксел
- Лапатиниб
Другие идентификационные номера исследования
- EGF102580
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. .