A Study of GFH276 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation
A Multi-center, Open-label Phase Ib/II Study Exploring the Safety/Tolerability, Pharmacokinetics, and Efficacy of GFH276 in Combination With Cetuximab or Chemotherapy in the Treatment of Patients With Advanced Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation
A Study of GFH276 Combined With Cetuximab or Chemotherapy in Participants With Solid Tumors and Pancreatic Ductal Adenocarcinoma (PDAC) Harboring RAS Mutation
Обзор исследования
Статус
Подробное описание
This is an open-label, multicenter Phase Ib/II clinical trial to evaluate the safety, tolerability, and preliminary anti-tumor efficacy of oral GFH276 in combination with cetuximab or standard chemotherapy in adult patients with locally advanced or metastatic RAS-mutated solid tumors and pancreatic ductal adenocarcinoma (PDAC).
Participants will be enrolled into three treatment arms with different combination regimens.
In the Phase Ib stage, dose escalation of GFH276 will be performed in each combination arm to identify the optimal recommended Phase 2 dose (RP2D) based on dose-limiting toxicity (DLT) and the overall safety profile. After RP2D determination, Phase II expansion cohorts will enroll eligible patients to further evaluate the anti-tumor efficacy and long-term safety of each combination regimen. Study-related assessments will include tumor imaging, laboratory tests, adverse event monitoring, and pharmacokinetic sampling throughout the treatment period.
Participants will continue their assigned study treatment until confirmed disease progression, intolerable toxicity, withdrawal of consent, or study closure.
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 2
- Фаза 1
Контакты и местонахождение
Контакты исследования
- Имя: Bai Li
- Номер телефона: 18201333260
- Электронная почта: lbai@genfleet.com
Учебное резервное копирование контактов
- Имя: Zhang Pingping
- Номер телефона: 18758558734
- Электронная почта: ppzhang@genfleet.com
Места учебы
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New South Wales
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Concord, New South Wales, Австралия, 2139
- Еще не набирают
- Concord Cancer Centre, Concord Repatriation General Hospital, Sydney Local Health District
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Контакт:
- Kim Tam B Bui, MBBS
- Номер телефона: 0297674425
- Электронная почта: Tam.Bui@health.nsw.gov.au
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North Ryde, New South Wales, Австралия, 2109
- Рекрутинг
- Macquarie University / Clinical Trials Unit
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Контакт:
- PhD
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Контакт:
- Andrew Parsonson, PhD
- Номер телефона: 0298122956
- Электронная почта: andrew.parsonson@mqhealth.org.au
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South Australia
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Woodville South, South Australia, Австралия, 5011
- Еще не набирают
- The Queen Elizabeth Hospital
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Контакт:
- Timothy Price, MBBS
- Номер телефона: 0882227096
- Электронная почта: timothy.price@sa.gov.au
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Victoria
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Clayton, Victoria, Австралия, 3168
- Рекрутинг
- Monash Health (Monash Medical Centre)
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Контакт:
- David Lau, PhD
- Номер телефона: 0385722392
- Электронная почта: David.Lau@monashhealth.org
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Epping, Victoria, Австралия, 3076
- Еще не набирают
- Northern Health
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Контакт:
- Belinda Lee, MBBS
- Номер телефона: 0384058000
- Электронная почта: Belinda.Lee@nh.org.au
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Frankston, Victoria, Австралия, 3199
- Рекрутинг
- PASO Medical
-
Контакт:
- Vinod Ganju, MBBS
- Номер телефона: 0397815244
- Электронная почта: vg@paso.com.au
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Beijing Municipality
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Beijing, Beijing Municipality, Китай, 100730
- Рекрутинг
- Peking Union Medical College Hospital
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Контакт:
- Chunmei Bai, MD
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Guangdong
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Guangzhou, Guangdong, Китай, 510120
- Рекрутинг
- Sun Yat-sen Memorial Hospital, Sun Yat-sen University
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Контакт:
- Zhihua Li, MD
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Heilongjiang
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Harbin, Heilongjiang, Китай, 150081
- Еще не набирают
- The Third Affiliated Hospital (Cancer Hospital) of Harbin Medical University
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Контакт:
- Guangyu Wang, MD
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Henan
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Zhengzhou, Henan, Китай, 450052
- Рекрутинг
- The First Affiliated Hospital of Zhengzhou University
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Контакт:
- Hong Zong, MD
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Hubei
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Wuhan, Hubei, Китай, 430022
- Еще не набирают
- Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
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Контакт:
- Heshui Wu, MD
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Liaoning
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Shenyang, Liaoning, Китай, 110001
- Еще не набирают
- The First Affiliated Hospital of China Medical University
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Контакт:
- Xiujuan Qu, MD
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Shaanxi
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Xi'an, Shaanxi, Китай, 710061
- Еще не набирают
- The First Affiliated Hospital of Xi'an Jiaotong University
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Контакт:
- Yinying Wu, MD
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Shandong
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Jinan, Shandong, Китай, 250117
- Рекрутинг
- Shandong First Medical University Affiliated Tumor Hospital
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Контакт:
- Shuqin Ni, MD
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Shanghai Municipality
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Shanghai, Shanghai Municipality, Китай, 200032
- Рекрутинг
- Fudan University Shanghai Cancer Center
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Контакт:
- Xianjun Yu, MD
- Номер телефона: 13801669875
- Электронная почта: yuxianjun@fudanpci.org
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Sichuan
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Chengdu, Sichuan, Китай, 610041
- Рекрутинг
- West China Hospital of Sichuan University
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Контакт:
- Xuelei Ma, MD
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Zhejiang
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Hangzhou, Zhejiang, Китай, 310016
- Рекрутинг
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
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Контакт:
- Da Li, MD
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria:
- Age ≥ 18 years
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor and PDAC with RAS mutation or KRAS amplification
- At least one measurable lesion according to RECIST v1.1
- ECOG performance status 0 or 1
- Life expectancy > 3 months
- Adequate organ function
- Willing to provide written informed consent
- Fertile participants must use effective contraception
Exclusion Criteria:
- Other active malignancy within 3 years
- Symptomatic brain metastases, leptomeningeal disease, spinal cord compression, or primary brain tumor
- History of active clinically significant cardiovascular dysfunction
- For participants with known concomitant second oncodriver for PDAC or for solid tumors.
- With active infection (HIV, HBV, HCV, syphilis)
- The presence of clinical or radiological evidence of intestinal obstruction.
- Prior anticancer therapy within 28 days or 5 half-lives
- Diagnosis of deep vein thrombosis or pulmonary embolism within 3 months
- Hypersensitivity to study drugs, or inability to swallow tablets or comply with study procedures.
- History of central nervous system (CNS)disease
- Presence of clinically significant interstitial lung disease, radiation pneumonitis, or immune-related pneumonia that requires treatment.
- With uncontrollable or symptomatic pleural effusion, ascites, or pericardial effusion.
Учебный план
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 |
|---|---|
|
Экспериментальный: Arm A: GFH276 + Cetuximab
GFH276 once daily; cetuximab 500 mg/m² intravenous infusion every 2 weeks. |
Oral GFH276 administered once daily in combination with other study drugs. Intravenous cetuximab at a dose of 500 mg/m² |
|
Экспериментальный: Arm B: GFH276 + AG
GFH276 once daily; nab-paclitaxel 125 mg/m² + gemcitabine 1000 mg/m² (AG regimen); 4-week cycle (D1, D8, D15) or 3-week cycle (D1, D8) in China |
Oral GFH276 administered once daily in combination with other study drugs. Intravenous nab-paclitaxel at a dose of 125 mg/m². Intravenous Gemcitabine at a dose of 1000 mg/m². |
|
Экспериментальный: Arm C: GFH276 + mFOLFIRINOX
GFH276 once daily; mFOLFIRINOX :Fluorouracil 2400 mg/m²(46 h), Leucovorin 400 mg/m², Irinotecan 150 mg/m², Oxaliplatin 85 mg/m², IV D1, every 2 weeks . The mFOLFIRINOX regimen may be administered per the above dosage, or in accordance with national or institutional guidelines. |
Oral GFH276 administered once daily in combination with other study drugs. Intravenous Fluorouracil at a dose of 2400 mg/m² via 46-hour infusion.Dosing may follow the above regimen or local institutional standards. Intravenous leucovorin at a dose of 400 mg/m².Dosing may follow the above regimen or local institutional standards. Intravenous irinotecan at a dose of 150 mg/m².Dosing may follow the above regimen or local institutional standards. Intravenous oxaliplatin at a dose of 85 mg/m².Dosing may follow the above regimen or local institutional standards. |
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Phase Ib:Incidence of Dose-Limiting Toxicity (DLT) Events
Временное ограничение: First 28 days (21 days for AG （3-week cycle）)
|
The incidence of DLT events |
First 28 days (21 days for AG （3-week cycle）)
|
|
Phase Ib:Incidence and Severity of Adverse Events (AE) and Serious Adverse Events (SAE)
Временное ограничение: From the first dose until 30 days after the last dose, assessed up to 24 months
|
The incidence and severity of AEs and SAEs，according to NCI CTCAE，v6.0 |
From the first dose until 30 days after the last dose, assessed up to 24 months
|
|
Phase II:Objective Response Rate (ORR)
Временное ограничение: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Assessed by investigators according to RECIST 1.1 |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
|
Phase Ib: Number of participants with abnormality in hematology laboratory parameters
Временное ограничение: up to 24 months
|
Number of participants with abnormality in hematology laboratory parameters，Hematology assessments will include hemoglobin, white blood cell count, differential white blood cell counts and platelet count |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in clinical chemistry laboratory assessments
Временное ограничение: up to 24 months
|
Number of participants with abnormality in clinical chemistry laboratory assessments， assessments will include serum chemistry (such as sodium, potassium, urea, creatinine) and liver function parameters, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) and bilirubin. |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in body temperature
Временное ограничение: up to 24 months
|
Number of participants with abnormality in body temperature(°C), throughout the study. |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in blood pressure
Временное ограничение: up to 24 months
|
Number of participants with abnormality in blood pressure, including systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in Physical Examination Findings
Временное ограничение: up to 24 months
|
Number of participants with abnormality in Physical Examination Findings |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in PR interval
Временное ограничение: up to 24 months
|
Number of participants with abnormality in electrocardiogram (ECG) parameters, including PR interval |
up to 24 months
|
|
Phase Ib: Number of participants with abnormality in corrected QT interval using Frederica's formula (QTcF)
Временное ограничение: up to 24 months
|
Number of participants with abnormality incorrected QT interval using Frederica's formula (QTcF) |
up to 24 months
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
Phase II: Incidence and Severity of AE and SAE
Временное ограничение: From the first dose until 30 days after the last dose, assessed up to 24 months
|
Incidence and Severity of AE and SAE，Assessed according to CTCAE 6.0 |
From the first dose until 30 days after the last dose, assessed up to 24 months
|
|
DCR
Временное ограничение: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Disease Control Rate (DCR) |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
|
DoR
Временное ограничение: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Duration of Response assessed by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
|
TTR
Временное ограничение: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Time To Response assessed by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
|
PFS
Временное ограничение: From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
Progression-Free Survival (PFS) per Response Evaluation Criteria according to RECIST 1.1, as Determined by investigators |
From the first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
|
|
OS
Временное ограничение: From the first dose until date of death from any cause, assessed up to 24 months
|
Overall Survival |
From the first dose until date of death from any cause, assessed up to 24 months
|
|
Time to peak plasma concentration（Tmax） of GFH276
Временное ограничение: up to 6 months
|
Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including Tmax were evaluated. |
up to 6 months
|
|
Maximum plasma concentration of GFH276
Временное ограничение: up to 6 months
|
Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including Cmax were evaluated. |
up to 6 months
|
|
Area Under the Curve from time zero to 24 hours of GFH276
Временное ограничение: up to 6 months
|
Plasma concentrations of GFH276 and relevant pharmacokinetic parameters including AUC0-24 were evaluated. |
up to 6 months
|
Соавторы и исследователи
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Дополнительные соответствующие термины MeSH
- Аминокислоты, пептиды и белки
- Белки
- Органические химические вещества
- 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
- Координационные комплексы
- Дезоксицитидин
- Цитидин
- Пиримидиновые нуклеозиды
- Пиримидины
- Экономика здравоохранения и организации
- Формилтетрагидрофолаты
- Тетрагидрофолаты
- Фолиевая кислота
- Птерины
- Птеридины
- Урацил
- Пиримидиноны
- Коэнзименты
- Экономика
- Оксалиплатин
- Иринотекан
- Цетуксимаб
- Гемцитабин
- Фторурацил
- Лейковорин
- Налоги
Другие идентификационные номера исследования
- GFH276X0201
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
продукт, произведенный в США и экспортированный из США.
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. .