Badanie wielu terapii u pacjentów z wyselekcjonowanymi biomarkerami w stadium IB-III niedrobnokomórkowego raka płuca kwalifikujących się do resekcji (NAUTIKA1)
NAUTIKA1: Wieloośrodkowe badanie fazy II, neoadiuwantowe i adjuwantowe, dotyczące wielu terapii u pacjentów z wyselekcjonowanymi biomarkerami w stadium IB-III niedrobnokomórkowego raka płuca
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.
Przegląd badań
Status
Warunki
Typ studiów
Zapisy (Szacowany)
Faza
- Faza 2
Kontakty i lokalizacje
Lokalizacje studiów
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California
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Los Angeles, California, Stany Zjednoczone, 90095
- University of California Los Angeles - Jonsson Comprehensive Cancer Center
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Orange, California, Stany Zjednoczone, 92868
- The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
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Sacramento, California, Stany Zjednoczone, 95817
- UC Davis Comprehensive Cancer Center
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Connecticut
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New Haven, Connecticut, Stany Zjednoczone, 06511
- Yale Cancer Center
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District of Columbia
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Washington D.C., District of Columbia, Stany Zjednoczone, 20007
- MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
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Florida
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Tampa, Florida, Stany Zjednoczone, 33612
- Moffitt Cancer Center
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Illinois
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Chicago, Illinois, Stany Zjednoczone, 60611
- Northwestern University
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DeKalb, Illinois, Stany Zjednoczone, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Geneva, Illinois, Stany Zjednoczone, 60134
- Northwestern Medicine Cancer Center Delnor
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Warrenville, Illinois, Stany Zjednoczone, 60555
- Northwestern Medicine Cancer Center Warrenville
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Massachusetts
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Boston, Massachusetts, Stany Zjednoczone, 02215
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Stany Zjednoczone, 48109
- University of Michigan
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Minnesota
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Rochester, Minnesota, Stany Zjednoczone, 55905
- Mayo Clinic
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Missouri
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Columbia, Missouri, Stany Zjednoczone, 65201
- Ellis Fischel Cancer Center
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St Louis, Missouri, Stany Zjednoczone, 63108
- Siteman Cancer Center - Washington University Medical Campus
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New Hampshire
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Lebanon, New Hampshire, Stany Zjednoczone, 03756
- Dartmouth Hitchcock Medical Center
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New York
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New York, New York, Stany Zjednoczone, 10032
- Columbia University Medical Center
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New York, New York, Stany Zjednoczone, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Stany Zjednoczone, 10016
- Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
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Ohio
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Columbus, Ohio, Stany Zjednoczone, 43210
- Ohio State University
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Pennsylvania
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Pittsburgh, Pennsylvania, Stany Zjednoczone, 15212
- AHN Cancer Institute ? Allegheny General Hospital
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Tennessee
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Memphis, Tennessee, Stany Zjednoczone, 38120
- Baptist Clinical Research Institute
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Texas
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Houston, Texas, Stany Zjednoczone, 77030-4008
- University of Texas MD Anderson Cancer Center
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Virginia
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Fairfax, Virginia, Stany Zjednoczone, 22031
- Virginia Cancer Specialists (Fairfax) - USOR
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Kryteria uczestnictwa
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
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
Plan studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Nielosowe
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Broń i interwencje
Grupa uczestników / Arm |
Interwencja / Leczenie |
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Eksperymentalny: 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).
Inne nazwy:
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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Eksperymentalny: 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.
Inne nazwy:
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Eksperymentalny: 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.
Inne nazwy:
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Eksperymentalny: 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.
Inne nazwy:
Participants will receive oral cobimetinib daily.
Inne nazwy:
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Eksperymentalny: 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.
Inne nazwy:
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Eksperymentalny: 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.
Inne nazwy:
Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab. |
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Eksperymentalny: 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.
Inne nazwy:
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Co mierzy badanie?
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
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KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs)
Ramy czasowe: 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
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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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Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
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Regresja patologiczna oparta na ocenie ważonego % żywotnych komórek nowotworowych
Ramy czasowe: Po resekcji chirurgicznej (około 8. tygodnia badania)
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Po resekcji chirurgicznej (około 8. tygodnia badania)
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Wskaźnik obiektywnej odpowiedzi (ORR) w ocenie badacza według kryteriów oceny odpowiedzi w guzach litych, wersja 1.1 (RECIST v1.1)
Ramy czasowe: Po leczeniu neoadiuwantowym (po około 8. tygodniu badania)
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Po leczeniu neoadiuwantowym (po około 8. tygodniu badania)
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Przeżycie wolne od choroby (DFS)
Ramy czasowe: Od pierwszego dnia braku choroby do nawrotu lokalnego lub odległego albo śmierci z jakiejkolwiek przyczyny, w zależności od tego, co nastąpi wcześniej, do zakończenia badania (do 9 lat)
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Od pierwszego dnia braku choroby do nawrotu lokalnego lub odległego albo śmierci z jakiejkolwiek przyczyny, w zależności od tego, co nastąpi wcześniej, do zakończenia badania (do 9 lat)
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Przetrwanie bez zdarzeń (EFS)
Ramy czasowe: Od pierwszej dawki badanego leku do pierwszej udokumentowanej progresji choroby zgodnie z RECIST v1.1 lub lokalnego lub odległego nawrotu choroby według oceny badacza lub śmierci z jakiejkolwiek przyczyny, w zależności od tego, która z tych sytuacji nastąpi wcześniej, do końca badania (do 9 lat)
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Od pierwszej dawki badanego leku do pierwszej udokumentowanej progresji choroby zgodnie z RECIST v1.1 lub lokalnego lub odległego nawrotu choroby według oceny badacza lub śmierci z jakiejkolwiek przyczyny, w zależności od tego, która z tych sytuacji nastąpi wcześniej, do końca badania (do 9 lat)
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Całkowite przeżycie (OS)
Ramy czasowe: Od pierwszej dawki badanego leku do śmierci z dowolnej przyczyny, aż do zakończenia badania (do 9 lat)
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Od pierwszej dawki badanego leku do śmierci z dowolnej przyczyny, aż do zakończenia badania (do 9 lat)
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Wskaźnik usuwania krążącego DNA guza (ctDNA).
Ramy czasowe: Przed operacją (przed 8. tygodniem badania)
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Przed operacją (przed 8. tygodniem badania)
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Percentage of Participants With AEs
Ramy czasowe: Up to 9 years
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Up to 9 years
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Proportion of Participants With MPR
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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
Ramy czasowe: 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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Współpracownicy i badacze
Sponsor
Śledczy
- Dyrektor Studium: Clinical Trials, Hoffmann-La Roche
Publikacje i pomocne linki
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Zakończenie podstawowe (Szacowany)
Ukończenie studiów (Szacowany)
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Dodatkowe istotne warunki MeSH
- Nowotwory według lokalizacji
- Nowotwory
- Choroby Układu Oddechowego
- Choroby płuc
- Nowotwory Układu Oddechowego
- Nowotwory klatki piersiowej
- Nowotwory płuc
- Rak, Bronchogenny
- Nowotwory oskrzeli
- Rak, płuco niedrobnokomórkowe
- Związki siarki
- Organiczne chemikalia
- Związki heterocykliczne
- Związki heterocykliczne, 2-ring
- Związki heterocykliczne, sterowanie stopieniem
- Lecznictwo
- Amides
- Indole
- Sulfonamidy
- Sulfony
- Wemurafenib
- Terapia lecznicza
- Atezolizumab
- Kobymetinib
- Entrectinib
- Alectinib
- Pralsetynib
Inne numery identyfikacyjne badania
- ML41591
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Opis planu 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
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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