A Study of Vemurafenib in Previously Treated Patients With Metastatic Melanoma
26 июня 2017 г. обновлено: Hoffmann-La Roche
An Open-label Multicenter Study on the Efficacy of Continuous Oral Dosing of Vemurafenib on Tumour Response in Previously Treated Patients With Metastatic Melanoma
This open-label single arm study will assess the efficacy, safety and tolerability of Vemurafenib in previously treated patients with metastatic melanoma.
Patients will receive oral Vemurafenib [RG7204; PLEXXIKON: PLX4032] at a dose of 960 mg b.i.d.
continuously until disease progression or withdrawal from study and will be assessed at regular intervals for tumour response and tolerability.
Target sample size is <100 patients.
Обзор исследования
Тип исследования
Интервенционный
Регистрация (Действительный)
132
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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Newcastle, New South Wales, Австралия, 2298
- Calvary Mater Newcastle; Melanoma Clinic
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Westmead, New South Wales, Австралия, 2145
- Westmead Hospital; Medical Oncology and Pallative Care
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Victoria
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Melbourne, Victoria, Австралия, 3000
- Peter Maccallum Cancer Institute; Medical Oncology
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California
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Los Angeles, California, Соединенные Штаты, 90095-6984
- UCLA - School of Medicine; Division of Hematology/Oncology
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Colorado
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Denver, Colorado, Соединенные Штаты, 80262
- University of Colorado
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Florida
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Tampa, Florida, Соединенные Штаты, 33612
- Moffitt Cancer Center
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Massachusetts
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Boston, Massachusetts, Соединенные Штаты, 02215
- Beth Israel Deaconess Medical Center
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Boston, Massachusetts, Соединенные Штаты, 02115
- Dana Farber Cancer Inst. ; Dept. of Medical Oncology
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Boston, Massachusetts, Соединенные Штаты, 02114
- Massachusetts General Hospital;Hematology/ Oncology
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New York
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New York, New York, Соединенные Штаты, 10036
- New York University Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, Соединенные Штаты, 19104-4283
- Hospital of the Uni of Pennsylvania; Section of Hematology/Oncology
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Pittsburgh, Pennsylvania, Соединенные Штаты, 15213
- University of Pittsburgh
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Tennessee
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Nashville, Tennessee, Соединенные Штаты, 37232
- Vanderbilt-Ingram Cancer Ctr
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Texas
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Dallas, Texas, Соединенные Штаты, 75246
- Texas Oncology-Baylor Sammons Cancer Center
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Houston, Texas, Соединенные Штаты, 77030
- University of Texas M.D. Anderson Cancer Center
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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:
- adult patients >/=18 years of age
- histologically confirmed metastatic melanoma (Stage IV, AJCC)
- patients must have completed and failed at least one prior standard of care regimen (e.g. DTIC, temozolomide, etc.)
- BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay)
- measurable disease by RECIST criteria
- negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion
Exclusion Criteria:
- active CNS metastases on CT/MRI within 28 days prior to enrollment
- history of or known carcinomatous meningitis
- previous treatment with BRAF (sorafenib allowed) or MEK inhibitor
- cardiac dysrhythmias >2 NCI CTCAE or treatment with drugs with dysrhythmic potential
- uncontrolled hypertension(>150/100mmHg) despite optimal medical therapy
- infectious disease including HIV, HBV and HCV
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: Н/Д
- Интервенционная модель: Одногрупповое задание
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
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Экспериментальный: Одна рука
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960 mg b.i.d.
continuous oral dosing
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Best Overall Response (BOR) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Временное ограничение: From first treatment through September 27, 2010
|
BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
Patients who never received study treatment and treated patients without any post-baseline tumor assessments were considered as non-responders.
CR: Disappearance of all target lesions, all non-target lesions, and no new lesion.
Any pathological lymph nodes must have had reduction in the short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.
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From first treatment through September 27, 2010
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Best Overall Response (BOR) Assessed by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Временное ограничение: From first treatment through September 27, 2010
|
BOR was defined as a complete response (CR) or partial response (PR) confirmed per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
Patients who never received study treatment and treated patients without any post-baseline tumor assessments were considered as non-responders.
CR: Disappearance of all target lesions, all non-target lesions, and no new lesion.
Any pathological lymph nodes must have had reduction in the short axis to <10 mm.
PR: At least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesion.
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From first treatment through September 27, 2010
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Duration of Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Временное ограничение: From first treatment through September 27, 2010
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Duration of response was defined as the time interval between the date of the earliest qualifying response and the date of disease progression (PD) or death, only for those patients whose best overall response was complete response or partial response.
PD: At least 20% increase in the sum of diameters of target lesions compared to Nadir (smallest sum of diameters on-study), unequivocal progression of existing non-target lesions, or presence of new lesion.
For patients who were alive without progression, duration of response was censored on the date of the last evaluable tumor assessment.
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From first treatment through September 27, 2010
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Time to Response Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Временное ограничение: From first treatment through September 27, 2010
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Time to response was defined as the interval between the date of the first treatment and the date of the first documentation of confirmed complete response (CR) or partial response (PR), whichever occurred first.
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From first treatment through September 27, 2010
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Progression Free Survival (PFS) Assessed by an Independent Review Committee Using Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
Временное ограничение: From first treatment through September 27, 2010
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PFS was defined the time interval between the date of the first treatment and the date of progression or death from any cause, whichever occurred first.
Deaths that occurred in patients without disease progression were considered to be a PFS event on the date of death.
Patients who neither progressed nor died were censored on the date of the last evaluable tumor assessment prior to the data cutoff date.
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From first treatment through September 27, 2010
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Overall Survival
Временное ограничение: From first treatment through September 27, 2010
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Overall survival was defined as the time from the date of the first treatment to the date of death, regardless of the cause of death.
For patients who were alive at the time of analysis, overall survival was censored at the last date the patient was known to be alive prior to the data cutoff date.
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From first treatment through September 27, 2010
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Improvement in Physical Symptoms (Improvement in Physician's Assessment of Global Performance Status and Oxygen Saturation Requirements, and Decrease in Total Dose and Frequency of Narcotic Pain Analgesics) During Treatment in Comparison to Baseline
Временное ограничение: From first treatment through September 27, 2010
|
Three parameters were measured.
(1) Improvement in the Physician's Assessment of Global Performance status on a 7-point scale (1=very much better to 7=very much worse).
(2) Improvement in oxygen saturation requirements, defined as a clinically meaningful increase in oxygen saturation requirement (from a baseline value < 95% to ≥ 95% saturation using a pulse oximeter).
(3) A decrease in total dose and frequency of narcotic pain analgesics.
The percentage of patients showing improvement (1 and 2) or a decrease (3) are reported.
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From first treatment through September 27, 2010
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Maximum Plasma Concentration (Cmax) of Vemurafenib on Day 15 of Cycle 1
Временное ограничение: Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Blood samples for assessing the concentration of vemurafenib in plasma were drawn before the morning dose and at 2, 4, 6, and 8 hours post-dose on Day 15 of Cycle 1. Pharmacokinetic parameters were estimated by non-compartmental analysis (Win Non-Lin).
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Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Vemurafenib Plasma Level Area Under the Curve From 0 to 8 Hours (AUC0-8h) on Day 15 of Cycle 1
Временное ограничение: Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Blood samples for assessing the concentration of vemurafenib in plasma were drawn before the morning dose and at 2, 4, 6, and 8 hours post-dose on Day 15 of Cycle 1. Pharmacokinetic parameters were estimated by non-compartmental analysis (Win Non-Lin).
AUC0-8h was calculated using the linear trapezoidal rule.
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Pre-dose to 8 hours post-dose on Day 15 of Cycle 1
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Vemurafenib Plasma Levels at Various Treatment Cycles
Временное ограничение: Pre-dose Cycle 1 Day 1 to 4 hours post-dose Cycle 10 Day 1
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Blood samples for assessing the concentration of vemurafenib in plasma were drawn before the morning dose and 4 hours post-dose at Day 1 of Cycles 1, 2, 3, 4, 6, 8, and 10.
Each Cycle was 3 weeks in duration.
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Pre-dose Cycle 1 Day 1 to 4 hours post-dose Cycle 10 Day 1
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Time-matched Change From Baseline in the Study Specific Corrected QT Interval (QTcP)
Временное ограничение: Pre-dose Cycle 1 Day 1 to pre-dose Cycle 6 Day 1
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Three electrocardiograms (ECG) were obtained pre-dose and 2, 4, 6, and 8 hours post-dose at Days 1 and 15 of Cycle 1 and again pre-dose and 4 hours post-dose at various Cycles throughout treatment.
Five baseline triplicate ECGs were obtained before the start of treatment at the same time points used during treatment.
Reported is the largest mean time-matched QTcP change from baseline.
QTcP=QT/(60/heart rate)^β (β=mean [calculated separately for males and females] log-transformed QT versus log-transformed RR regression slopes using all available pre-treatment (baseline) ECG values.
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Pre-dose Cycle 1 Day 1 to pre-dose Cycle 6 Day 1
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Percentage of Patients With Adverse Event
Временное ограничение: From first treatment through September 27, 2010
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The intensity of adverse events was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v 4.0 (CTCAE) on a 5-point scale (Grade 1 to 5: Mild, Moderate, Severe, Life-threatening, and Death).
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From first treatment through September 27, 2010
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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.
Общие публикации
- Su F, Viros A, Milagre C, Trunzer K, Bollag G, Spleiss O, Reis-Filho JS, Kong X, Koya RC, Flaherty KT, Chapman PB, Kim MJ, Hayward R, Martin M, Yang H, Wang Q, Hilton H, Hang JS, Noe J, Lambros M, Geyer F, Dhomen N, Niculescu-Duvaz I, Zambon A, Niculescu-Duvaz D, Preece N, Robert L, Otte NJ, Mok S, Kee D, Ma Y, Zhang C, Habets G, Burton EA, Wong B, Nguyen H, Kockx M, Andries L, Lestini B, Nolop KB, Lee RJ, Joe AK, Troy JL, Gonzalez R, Hutson TE, Puzanov I, Chmielowski B, Springer CJ, McArthur GA, Sosman JA, Lo RS, Ribas A, Marais R. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med. 2012 Jan 19;366(3):207-15. doi: 10.1056/NEJMoa1105358.
- Frederick DT, Salas Fragomeni RA, Schalck A, Ferreiro-Neira I, Hoff T, Cooper ZA, Haq R, Panka DJ, Kwong LN, Davies MA, Cusack JC, Flaherty KT, Fisher DE, Mier JW, Wargo JA, Sullivan RJ. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. PLoS One. 2014 Jul 1;9(7):e101286. doi: 10.1371/journal.pone.0101286. eCollection 2014.
- Lacouture ME, Duvic M, Hauschild A, Prieto VG, Robert C, Schadendorf D, Kim CC, McCormack CJ, Myskowski PL, Spleiss O, Trunzer K, Su F, Nelson B, Nolop KB, Grippo JF, Lee RJ, Klimek MJ, Troy JL, Joe AK. Analysis of dermatologic events in vemurafenib-treated patients with melanoma. Oncologist. 2013;18(3):314-22. doi: 10.1634/theoncologist.2012-0333. Epub 2013 Mar 1.
- Ascierto PA, Ribas A, Larkin J, McArthur GA, Lewis KD, Hauschild A, Flaherty KT, McKenna E, Zhu Q, Mun Y, Dreno B. Impact of initial treatment and prognostic factors on postprogression survival in BRAF-mutated metastatic melanoma treated with dacarbazine or vemurafenib +/- cobimetinib: a pooled analysis of four clinical trials. J Transl Med. 2020 Aug 3;18(1):294. doi: 10.1186/s12967-020-02458-x.
- Sosman JA, Kim KB, Schuchter L, Gonzalez R, Pavlick AC, Weber JS, McArthur GA, Hutson TE, Moschos SJ, Flaherty KT, Hersey P, Kefford R, Lawrence D, Puzanov I, Lewis KD, Amaravadi RK, Chmielowski B, Lawrence HJ, Shyr Y, Ye F, Li J, Nolop KB, Lee RJ, Joe AK, Ribas A. Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med. 2012 Feb 23;366(8):707-14. doi: 10.1056/NEJMoa1112302.
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)
30 сентября 2009 г.
Первичное завершение (Действительный)
27 сентября 2010 г.
Завершение исследования (Действительный)
3 июня 2014 г.
Даты регистрации исследования
Первый отправленный
28 июля 2009 г.
Впервые представлено, что соответствует критериям контроля качества
29 июля 2009 г.
Первый опубликованный (Оценивать)
30 июля 2009 г.
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
25 июля 2017 г.
Последнее отправленное обновление, отвечающее критериям контроля качества
26 июня 2017 г.
Последняя проверка
1 июня 2017 г.
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
- Новообразования по гистологическому типу
- Новообразования
- Нейроэктодермальные опухоли
- Новообразования, зародышевые клетки и эмбриональные
- Новообразования, нервная ткань
- Нейроэндокринные опухоли
- Невусы и меланомы
- Меланома
- Молекулярные механизмы фармакологического действия
- Ингибиторы ферментов
- Противоопухолевые агенты
- Ингибиторы протеинкиназы
- Вемурафениб
Другие идентификационные номера исследования
- NP22657
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. .