Исследование множественной терапии у пациентов, отобранных по биомаркерам, с резектабельным немелкоклеточным раком легкого на стадиях IB-III (NAUTIKA1)
NAUTIKA1: Многоцентровое неоадъювантное и адъювантное исследование фазы II множественной терапии у пациентов с операбельным немелкоклеточным раком легкого на стадиях IB-III, отобранных с помощью биомаркеров
This trial will evaluate the efficacy and safety of various therapies in participants with Stage IB, IIA, IIB, IIIA, or selected IIIB resectable and untreated NSCLC tumors that meet protocol-specified biomarker criteria.
Обзор исследования
Статус
Условия
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 2
Контакты и местонахождение
Места учебы
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California
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Los Angeles, California, Соединенные Штаты, 90095
- University of California Los Angeles - Jonsson Comprehensive Cancer Center
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Orange, California, Соединенные Штаты, 92868
- The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
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Sacramento, California, Соединенные Штаты, 95817
- UC Davis Comprehensive Cancer Center
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Connecticut
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New Haven, Connecticut, Соединенные Штаты, 06511
- Yale Cancer Center
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District of Columbia
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Washington D.C., District of Columbia, Соединенные Штаты, 20007
- MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
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Florida
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Tampa, Florida, Соединенные Штаты, 33612
- Moffitt Cancer Center
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Illinois
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Chicago, Illinois, Соединенные Штаты, 60611
- Northwestern University
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DeKalb, Illinois, Соединенные Штаты, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Geneva, Illinois, Соединенные Штаты, 60134
- Northwestern Medicine Cancer Center Delnor
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Warrenville, Illinois, Соединенные Штаты, 60555
- Northwestern Medicine Cancer Center Warrenville
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Massachusetts
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Boston, Massachusetts, Соединенные Штаты, 02215
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Соединенные Штаты, 48109
- University of Michigan
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Minnesota
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Rochester, Minnesota, Соединенные Штаты, 55905
- Mayo Clinic
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Missouri
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Columbia, Missouri, Соединенные Штаты, 65201
- Ellis Fischel Cancer Center
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St Louis, Missouri, Соединенные Штаты, 63108
- Siteman Cancer Center - Washington University Medical Campus
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New Hampshire
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Lebanon, New Hampshire, Соединенные Штаты, 03756
- Dartmouth Hitchcock Medical Center
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New York
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New York, New York, Соединенные Штаты, 10032
- Columbia University Medical Center
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New York, New York, Соединенные Штаты, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Соединенные Штаты, 10016
- Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
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Ohio
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Columbus, Ohio, Соединенные Штаты, 43210
- Ohio State University
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Pennsylvania
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Pittsburgh, Pennsylvania, Соединенные Штаты, 15212
- AHN Cancer Institute ? Allegheny General Hospital
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Tennessee
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Memphis, Tennessee, Соединенные Штаты, 38120
- Baptist Clinical Research Institute
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Texas
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Houston, Texas, Соединенные Штаты, 77030-4008
- University of Texas MD Anderson Cancer Center
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Virginia
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Fairfax, Virginia, Соединенные Штаты, 22031
- Virginia Cancer Specialists (Fairfax) - USOR
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
Inclusion Criteria for Neoadjuvant Therapy:
- Pathologically documented NSCLC:
- Newly diagnosed early-stage NSCLC stages IB, IIA, IIB, IIIA, or selected IIIB (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on the 8th edition of the American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) NSCLC staging system
- T4 primary NSCLC will be allowed only on the basis of size. Invasion of the diaphragm, mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina, and separate tumor nodules in a different ipsilateral lobe is not permitted
- All participants will undergo clinical staging using computed tomography (CT) and positron emission tomography (PET) scanning, as well as brain imaging using magnetic resonance imaging (MRI). Invasive mediastinal staging by either mediastinoscopy or endo-bronchial ultrasonography is highly encouraged for participants with radiographically suspected mediastinal nodal disease (i.e., N2) but not mandated if the CT or PET scans showed no evidence of N2 disease
- Molecular testing results from clinical laboratory improvement amendments (CLIA)-certified laboratories and showing at least one of the following abnormalities: ALK fusion, ROS1 fusion, NTRK1/2/3 fusion; BRAF V600 mutation, RET fusion, PD-L1 expression in ≥ 1% tumor cells as determined by Food and Drug Administration (FDA)-approved test, KRAS G12C mutation
- Measurable disease, as defined by RECIST v1.1
- NSCLC must have a solid or subsolid appearance on CT scan and cannot have a purely ground glass opacity appearance. For subsolid lesions, the tumor size (i.e., clinical T stage) should be measured based on the solid component only, exclusive of the ground glass opacity component
- Evaluated by the attending surgeon prior to study enrollment to verify that the primary tumor and any involved lymph nodes are technically completely resectable and verify that the participant is medically operable
- Adequate pulmonary function to be eligible for surgical resection with curative intent
- Adequate cardiac function to be eligible for surgical resection with curative intent
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Adequate hematologic and end-organ function
- Negative hepatitis B surface antigen (HBsAg) test at screening for cohort
- Negative total hepatitits B core antibody (HBcAb) test at screening for cohort, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test at screening
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening
- Male participants must be willing to use acceptable methods of contraception
- Female participants of childbearing potential must agree to use acceptable methods of contraception
Inclusion Criteria for Adjuvant Therapy (TKI Cohorts and KRAS G12C cohort [if continuing on Divarasib]):
- Participants whose tumors lack radiographic progression
- ECOG Performance Status of 0 or 1
- Adequate hematologic and end-organ function
Exclusion Criteria
- NSCLC that is clinically T4 by virtue of mediastinal organ invasion or Stage IIIB by virtue of N3 disease
- Any prior therapy for lung cancer, including chemotherapy, targeted therapy, immunotherapy, or radiotherapy, within 2 years
- Participants with prior lung cancer
- Major surgical procedure within 28 days prior to Cycle 1, Day 1
- Malignancies other than the disease under study within 3 years prior to Cycle 1, Day 1, with the exception of participants with a negligible risk of metastasis or death and with expected curative outcome
- Treatment with an investigational agent for any condition within 4 weeks prior to Cycle 1, Day 1
- Participants known to be positive for human immunodeficiency virus (HIV) are excluded if they meet any of the following criteria: cluster of differentiation 4 (CD4)+ T-cell count of <350 cells/microliters (cells/µL); detectable HIV viral load; history of an opportunistic infection within the past 12 months; on stable antiretroviral therapy for <4 weeks
- Severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infections, or any active infection that, in the opinion of the investigator, could impact participant safety
- Pregnant or lactating, or intending to become pregnant during the study
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Нерандомизированный
- Интервенционная модель: Одногрупповое задание
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
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Экспериментальный: ALK Cohort (Enrolment Closed)
Participants will receive up to 8 weeks of alectinib neoadjuvant treatment before undergoing surgical resection per standard of care (SOC). All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with alectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of alectinib. Enrolment Closed. |
Participants will receive oral alectinib twice per day (BID).
Другие имена:
Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC. Participants will receive SOC chemotherapy as determined by the treating physician. |
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Экспериментальный: ROS 1 Cohort (Enrolment Closed)
Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib. Enrolment Closed. |
Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC. Participants will receive SOC chemotherapy as determined by the treating physician. Participants will receive oral entrectinib daily.
Другие имена:
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Экспериментальный: NTRK Cohort (Enrolment Closed)
Participants will receive up to 8 weeks of entrectinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with entrectinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of entrectinib. Enrolment Closed. |
Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC. Participants will receive SOC chemotherapy as determined by the treating physician. Participants will receive oral entrectinib daily.
Другие имена:
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Экспериментальный: BRAF Cohort (No Participants Enrolled, Cohort Closed)
Participants will receive up to 8 weeks of vemurafenib plus cobimetinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with vemurafenib plus cobimetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of of vemurafenib plus cobimetinib. Cohort closed. |
Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC. Participants will receive SOC chemotherapy as determined by the treating physician. Participants will receive oral vemurafenib BID.
Другие имена:
Participants will receive oral cobimetinib daily.
Другие имена:
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Экспериментальный: RET Cohort (Cohort closed)
Participants will receive up to 8 weeks of pralsetinib neoadjuvant treatment before undergoing surgical resection per SOC. All participants that undergo surgical resection and whose tumors have pathological response or lack radiographic progression will be eligible for the adjuvant treatment phase with pralsetinib. Adjuvant therapy will consist of 4 cycles of chemotherapy followed by up to 2 years of pralsetinib. Cohort closed. |
Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC. Participants will receive SOC chemotherapy as determined by the treating physician. Participants will receive oral pralsetinib daily.
Другие имена:
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Экспериментальный: PD-L1 Cohort (Enrolment Closed)
Participants with positive programmed death-ligand 1 (PD-L1) in ≥1% tumor cells will receive 4 cycles of atezolizumab neoadjuvant treatment. During neoadjuvant Cycle 1 of atezolizumab, participants will also receive low-dose stereotactic body radiation therapy (SBRT) (8 gray [Gy] X 3). Adjuvant treatment consists of SOC treatment as determined by the investigator, per National Comprehensive Cancer Network (NCCN) guidelines. Enrolment Closed. |
Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC. Atezolizumab will be administered by intravenous (IV) infusion.
Другие имена:
Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab. |
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Экспериментальный: KRAS G12C Cohort
Participants will receive up to 8 weeks of divarasib as neoadjuvant treatment before undergoing surgical resection per SOC. PD-L1 negative participants whose tumors have pathological response or lack radiographic progression will be have the option of continuing divarasib alone for up to 3 years or 1-4 cycles of SOC chemotherapy followed by divarasib for 3 years as adjuvant therapy. For participants who test positive PD-L1, they will have the option to receive 1-4 cycles of SOC chemotherapy followed by atezolizumab for up to 16 cycles or SOC alone. |
Participants will receive surgical resection of the primary tumor along with selected lymph nodes per SOC. Participants will receive SOC chemotherapy as determined by the treating physician. Participants in the KRAS G12C cohort will receive oral divarasib for approximately 8 weeks until the day before surgery as neoadjuvant therapy up to 3 years as adjuvant therapy.
Другие имена:
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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
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KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs)
Временное ограничение: After surgical resection (approximately study Week 8)
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After surgical resection (approximately study Week 8)
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KRAS G12C Cohort: Percentage of Participants Without Delays of Surgery due to Treatment-related AEs as Reported by the Investigator
Временное ограничение: After surgical resection (approximately study Week 8)
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After surgical resection (approximately study Week 8)
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Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR)
Временное ограничение: After surgical resection (approximately study Week 8)
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MPR is defined as ≤ 10% residual viable tumor cells as scored by local pathologists. |
After surgical resection (approximately study Week 8)
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Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR)
Временное ограничение: After surgical resection (approximately study Week 8)
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Scored by local pathologists; defined as lack of any viable tumor cells on review of hematoxylin and eosin (H&E) slides after complete evaluation of a resected lung cancer specimen including all sampled regional lymph nodes. |
After surgical resection (approximately study Week 8)
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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Патологическая регрессия, основанная на взвешенной оценке % жизнеспособных опухолевых клеток
Временное ограничение: После хирургической резекции (приблизительно 8-я неделя исследования)
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После хирургической резекции (приблизительно 8-я неделя исследования)
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Объективная частота ответа (ЧОО) по оценке исследователя на критерии оценки ответа при солидных опухолях, версия 1.1 (RECIST v1.1)
Временное ограничение: После неоадъювантного лечения (приблизительно после 8-й недели исследования)
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После неоадъювантного лечения (приблизительно после 8-й недели исследования)
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Выживание без болезней (DFS)
Временное ограничение: От первого дня отсутствия заболевания до местного или отдаленного рецидива или смерти по любой причине, в зависимости от того, что наступит раньше, до окончания исследования (до 9 лет)
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От первого дня отсутствия заболевания до местного или отдаленного рецидива или смерти по любой причине, в зависимости от того, что наступит раньше, до окончания исследования (до 9 лет)
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Выживание без событий (EFS)
Временное ограничение: От первой дозы исследуемого препарата до первого документально подтвержденного прогрессирования заболевания согласно RECIST v1.1 или местного или отдаленного рецидива заболевания по определению исследователя или смерти по любой причине, в зависимости от того, что наступит раньше, до окончания исследования (до 9 лет)
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От первой дозы исследуемого препарата до первого документально подтвержденного прогрессирования заболевания согласно RECIST v1.1 или местного или отдаленного рецидива заболевания по определению исследователя или смерти по любой причине, в зависимости от того, что наступит раньше, до окончания исследования (до 9 лет)
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Общая выживаемость (ОС)
Временное ограничение: От первой дозы исследуемого препарата до смерти по любой причине до окончания исследования (до 9 лет)
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От первой дозы исследуемого препарата до смерти по любой причине до окончания исследования (до 9 лет)
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Скорость выведения циркулирующей опухолевой ДНК (цДНК)
Временное ограничение: До операции (до 8-й недели исследования)
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До операции (до 8-й недели исследования)
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Percentage of Participants With AEs
Временное ограничение: Up to 9 years
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Up to 9 years
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Proportion of Participants With MPR
Временное ограничение: After surgical resection (approximately study Week 8)
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Defined as ≤10% residual viable tumor cells) based on surgical resection as defined by Hellmann et al. (2014) and Travis et al. (2020). TKI cohorts: MPR will be scored by a central pathology committee consensus read. CPI cohort: MPR will be scored by local pathologists and central pathology committee consensus read. KRAS G12C cohort: MPR will be scored by local pathologists and central pathology committee consensus read. |
After surgical resection (approximately study Week 8)
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Proportion of Participants With pCR
Временное ограничение: After surgical resection (approximately study Week 8)
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Defined as lack of any viable tumor cells on review of H&E slides after complete evaluation of a resected lung cancer specimen, including all sampled regional lymph nodes. TKI cohorts: pCR will be scored by local pathologists and a central pathology committee consensus read. CPI cohort: pCR will be scored by a central pathology committee consensus read. KRAS G12C cohort: pCR will be scored by a central pathology committee consensus read. |
After surgical resection (approximately study Week 8)
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Nodal Downstaging
Временное ограничение: After surgical resection (approximately study Week 8)
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Defined as percentage of participants with reduced stages in regional lymph nodes at surgery. |
After surgical resection (approximately study Week 8)
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KRAS G12C Cohort: Plasma Concentration of Divarasib at Specified Timepoints
Временное ограничение: Neo-adjuvant: pre-dose & 2 hours post-dose on Day 1 of Cycles 1 & 2; Pre-surgery (before Week 8): pre-dose; Adjuvant treatment: pre-dose & 2 hours post-dose on Day 1 of Cycles 1-6, pre-dose on Day 1 of Cycle 9 (each cycle=28 days);
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Neo-adjuvant: pre-dose & 2 hours post-dose on Day 1 of Cycles 1 & 2; Pre-surgery (before Week 8): pre-dose; Adjuvant treatment: pre-dose & 2 hours post-dose on Day 1 of Cycles 1-6, pre-dose on Day 1 of Cycle 9 (each cycle=28 days);
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Соавторы и исследователи
Спонсор
Следователи
- Директор по исследованиям: Clinical Trials, Hoffmann-La Roche
Публикации и полезные ссылки
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
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
Дополнительные соответствующие термины MeSH
- Новообразования по локализации
- Новообразования
- Заболевания дыхательных путей
- Легочные заболевания
- Новообразования дыхательных путей
- Грудные новообразования
- Новообразования легких
- Рак, Бронхогенный
- Бронхиальные новообразования
- Карцинома немелкоклеточного легкого
- Средние соединения
- Органические химические вещества
- Гетероциклические соединения
- Гетероциклические соединения, 2-кольцо
- Гетероциклические соединения, слитое кольцо
- Терапия
- Амиды
- Индолы
- Сульфонамиды
- Сульфоны
- Вемурафениб
- Лекарственная терапия
- Атезолизумаб
- кобиметиниб
- Entrectinib
- алектиниб
- Pralsetinib
Другие идентификационные номера исследования
- ML41591
Планирование данных отдельных участников (IPD)
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Описание плана IPD
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
Информация о лекарствах и устройствах, исследовательские документы
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