Uno studio sulle terapie multiple nei pazienti selezionati con biomarcatori con carcinoma polmonare non a piccole cellule in stadio resecabile IB-III (NAUTIKA1)
NAUTIKA1: studio multicentrico, di fase II, neoadiuvante e adiuvante di terapie multiple in pazienti selezionati con biomarcatori con carcinoma polmonare non a piccole cellule in stadio resecabile IB-III
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.
Panoramica dello studio
Stato
Condizioni
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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California
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Los Angeles, California, Stati Uniti, 90095
- University of California Los Angeles - Jonsson Comprehensive Cancer Center
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Orange, California, Stati Uniti, 92868
- The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
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Sacramento, California, Stati Uniti, 95817
- UC Davis Comprehensive Cancer Center
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Connecticut
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New Haven, Connecticut, Stati Uniti, 06511
- Yale Cancer Center
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District of Columbia
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Washington D.C., District of Columbia, Stati Uniti, 20007
- MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
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Florida
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Tampa, Florida, Stati Uniti, 33612
- Moffitt Cancer Center
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Illinois
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Chicago, Illinois, Stati Uniti, 60611
- Northwestern University
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DeKalb, Illinois, Stati Uniti, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Geneva, Illinois, Stati Uniti, 60134
- Northwestern Medicine Cancer Center Delnor
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Warrenville, Illinois, Stati Uniti, 60555
- Northwestern Medicine Cancer Center Warrenville
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02215
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Stati Uniti, 48109
- University of Michigan
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Minnesota
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Rochester, Minnesota, Stati Uniti, 55905
- Mayo Clinic
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Missouri
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Columbia, Missouri, Stati Uniti, 65201
- Ellis Fischel Cancer Center
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St Louis, Missouri, Stati Uniti, 63108
- Siteman Cancer Center - Washington University Medical Campus
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New Hampshire
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Lebanon, New Hampshire, Stati Uniti, 03756
- Dartmouth Hitchcock Medical Center
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New York
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New York, New York, Stati Uniti, 10032
- Columbia University Medical Center
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New York, New York, Stati Uniti, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Stati Uniti, 10016
- Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
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Ohio
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Columbus, Ohio, Stati Uniti, 43210
- Ohio State University
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Pennsylvania
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Pittsburgh, Pennsylvania, Stati Uniti, 15212
- AHN Cancer Institute ? Allegheny General Hospital
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Tennessee
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Memphis, Tennessee, Stati Uniti, 38120
- Baptist Clinical Research Institute
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Texas
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Houston, Texas, Stati Uniti, 77030-4008
- University of Texas MD Anderson Cancer Center
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Virginia
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Fairfax, Virginia, Stati Uniti, 22031
- Virginia Cancer Specialists (Fairfax) - USOR
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione di gruppo singolo
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Sperimentale: 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).
Altri nomi:
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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Sperimentale: 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.
Altri nomi:
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Sperimentale: 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.
Altri nomi:
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Sperimentale: 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.
Altri nomi:
Participants will receive oral cobimetinib daily.
Altri nomi:
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Sperimentale: 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.
Altri nomi:
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Sperimentale: 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.
Altri nomi:
Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab. |
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Sperimentale: 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.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs)
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Regressione patologica basata sulla valutazione della percentuale ponderata di cellule tumorali vitali
Lasso di tempo: Dopo resezione chirurgica (approssimativamente settimana 8 dello studio)
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Dopo resezione chirurgica (approssimativamente settimana 8 dello studio)
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Risposta Tasso di risposta obiettiva (ORR) valutato dallo sperimentatore in base ai criteri di valutazione della risposta nei tumori solidi Versione 1.1 (RECIST v1.1)
Lasso di tempo: Dopo il trattamento neoadiuvante (dopo circa la settimana 8 di studio)
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Dopo il trattamento neoadiuvante (dopo circa la settimana 8 di studio)
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Sopravvivenza libera da malattia (DFS)
Lasso di tempo: Dalla prima data di assenza di malattia alla recidiva locale o a distanza o alla morte per qualsiasi causa, a seconda di quale evento si verifichi per primo, fino alla fine dello studio (fino a 9 anni)
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Dalla prima data di assenza di malattia alla recidiva locale o a distanza o alla morte per qualsiasi causa, a seconda di quale evento si verifichi per primo, fino alla fine dello studio (fino a 9 anni)
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Sopravvivenza senza eventi (EFS)
Lasso di tempo: Dalla prima dose del trattamento in studio alla prima progressione della malattia documentata secondo RECIST v1.1, o recidiva della malattia locale o a distanza come determinato dallo sperimentatore, o morte per qualsiasi causa, a seconda di quale evento si verifichi per primo, fino alla fine dello studio (fino a 9 anni)
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Dalla prima dose del trattamento in studio alla prima progressione della malattia documentata secondo RECIST v1.1, o recidiva della malattia locale o a distanza come determinato dallo sperimentatore, o morte per qualsiasi causa, a seconda di quale evento si verifichi per primo, fino alla fine dello studio (fino a 9 anni)
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Sopravvivenza complessiva (OS)
Lasso di tempo: Dalla prima dose del farmaco in studio alla morte per qualsiasi causa, fino alla fine dello studio (fino a 9 anni)
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Dalla prima dose del farmaco in studio alla morte per qualsiasi causa, fino alla fine dello studio (fino a 9 anni)
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Tasso di eliminazione del DNA tumorale circolante (ctDNA).
Lasso di tempo: Prima dell'intervento chirurgico (prima della settimana 8 di studio)
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Prima dell'intervento chirurgico (prima della settimana 8 di studio)
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Percentage of Participants With AEs
Lasso di tempo: Up to 9 years
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Up to 9 years
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Proportion of Participants With MPR
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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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Collaboratori e investigatori
Sponsor
Investigatori
- Direttore dello studio: Clinical Trials, Hoffmann-La Roche
Pubblicazioni e link utili
Studiare le date dei record
Studia le date principali
Inizio studio (Effettivo)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
- Neoplasie per sede
- Neoplasie
- Malattie delle vie respiratorie
- Malattie polmonari
- Neoplasie delle vie respiratorie
- Neoplasie toraciche
- Neoplasie polmonari
- Carcinoma, broncogeno
- Neoplasie bronchiali
- Carcinoma, polmone non a piccole cellule
- Composti di zolfo
- Prodotti chimici organici
- Composti eterociclici
- Composti eterociclici, 2 anelli
- Composti eterociclici, anello fuso
- Terapie
- Amides
- Indoli
- Sulfonamidi
- Solfoni
- Vemurafenib
- Terapia farmacologica
- atezolizumab
- cobimetinib
- entrectinib
- alectinib
- pralsetinib
Altri numeri di identificazione dello studio
- ML41591
Piano per i dati dei singoli partecipanti (IPD)
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Descrizione del piano 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
Informazioni su farmaci e dispositivi, documenti di studio
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