Um estudo de múltiplas terapias em pacientes selecionados por biomarcadores com câncer de pulmão de células não pequenas Ressecável estágios IB-III (NAUTIKA1)
NAUTIKA1: Estudo Multicêntrico, Fase II, Neoadjuvante e Adjuvante de Terapias Múltiplas em Pacientes Selecionados por Biomarcadores com Câncer de Pulmão de Células Não Pequenas Ressecáveis Estágios 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.
Visão geral do estudo
Status
Condições
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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California
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Los Angeles, California, Estados Unidos, 90095
- University of California Los Angeles - Jonsson Comprehensive Cancer Center
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Orange, California, Estados Unidos, 92868
- The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
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Sacramento, California, Estados Unidos, 95817
- UC Davis Comprehensive Cancer Center
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Connecticut
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New Haven, Connecticut, Estados Unidos, 06511
- Yale Cancer Center
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District of Columbia
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Washington D.C., District of Columbia, Estados Unidos, 20007
- MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
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Florida
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Tampa, Florida, Estados Unidos, 33612
- Moffitt Cancer Center
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Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Northwestern University
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DeKalb, Illinois, Estados Unidos, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Geneva, Illinois, Estados Unidos, 60134
- Northwestern Medicine Cancer Center Delnor
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Warrenville, Illinois, Estados Unidos, 60555
- Northwestern Medicine Cancer Center Warrenville
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02215
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- University of Michigan
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Minnesota
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Rochester, Minnesota, Estados Unidos, 55905
- Mayo Clinic
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Missouri
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Columbia, Missouri, Estados Unidos, 65201
- Ellis Fischel Cancer Center
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St Louis, Missouri, Estados Unidos, 63108
- Siteman Cancer Center - Washington University Medical Campus
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New Hampshire
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Lebanon, New Hampshire, Estados Unidos, 03756
- Dartmouth Hitchcock Medical Center
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New York
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New York, New York, Estados Unidos, 10032
- Columbia University Medical Center
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New York, New York, Estados Unidos, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Estados Unidos, 10016
- Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
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Ohio
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Columbus, Ohio, Estados Unidos, 43210
- Ohio State University
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Pennsylvania
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Pittsburgh, Pennsylvania, Estados Unidos, 15212
- AHN Cancer Institute ? Allegheny General Hospital
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Tennessee
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Memphis, Tennessee, Estados Unidos, 38120
- Baptist Clinical Research Institute
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Texas
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Houston, Texas, Estados Unidos, 77030-4008
- University of Texas MD Anderson Cancer Center
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Virginia
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Fairfax, Virginia, Estados Unidos, 22031
- Virginia Cancer Specialists (Fairfax) - USOR
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição de grupo único
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
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Experimental: 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).
Outros nomes:
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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Experimental: 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.
Outros nomes:
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Experimental: 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.
Outros nomes:
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Experimental: 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.
Outros nomes:
Participants will receive oral cobimetinib daily.
Outros nomes:
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Experimental: 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.
Outros nomes:
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Experimental: 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.
Outros nomes:
Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab. |
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Experimental: 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.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
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KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs)
Prazo: 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
Prazo: 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)
Prazo: 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)
Prazo: 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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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
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Regressão patológica com base na % ponderada de avaliação de células tumorais viáveis
Prazo: Após a ressecção cirúrgica (aproximadamente na Semana 8 do estudo)
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Após a ressecção cirúrgica (aproximadamente na Semana 8 do estudo)
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Taxa de resposta objetiva (ORR) avaliada pelo investigador por critérios de avaliação de resposta em tumores sólidos versão 1.1 (RECIST v1.1)
Prazo: Após tratamento neoadjuvante (após aproximadamente a Semana 8 do estudo)
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Após tratamento neoadjuvante (após aproximadamente a Semana 8 do estudo)
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Sobrevivência Livre de Doença (DFS)
Prazo: Desde a primeira data de ausência de doença até a recorrência local ou distante ou morte por qualquer causa, o que ocorrer primeiro, até o final do estudo (até 9 anos)
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Desde a primeira data de ausência de doença até a recorrência local ou distante ou morte por qualquer causa, o que ocorrer primeiro, até o final do estudo (até 9 anos)
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Sobrevivência sem eventos (EFS)
Prazo: Desde a primeira dose do tratamento do estudo até a primeira progressão documentada da doença de acordo com RECIST v1.1, ou recorrência local ou distante da doença, conforme determinado pelo investigador, ou morte por qualquer causa, o que ocorrer primeiro, até o final do estudo (até 9 anos)
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Desde a primeira dose do tratamento do estudo até a primeira progressão documentada da doença de acordo com RECIST v1.1, ou recorrência local ou distante da doença, conforme determinado pelo investigador, ou morte por qualquer causa, o que ocorrer primeiro, até o final do estudo (até 9 anos)
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Sobrevivência Geral (OS)
Prazo: Desde a primeira dose da medicação do estudo até a morte por qualquer causa, até o final do estudo (até 9 anos)
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Desde a primeira dose da medicação do estudo até a morte por qualquer causa, até o final do estudo (até 9 anos)
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Taxa de eliminação de DNA tumoral circulante (ctDNA)
Prazo: Antes da cirurgia (antes da Semana 8 do estudo)
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Antes da cirurgia (antes da Semana 8 do estudo)
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Percentage of Participants With AEs
Prazo: Up to 9 years
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Up to 9 years
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Proportion of Participants With MPR
Prazo: 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
Prazo: 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
Prazo: 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
Prazo: 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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Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Clinical Trials, Hoffmann-La Roche
Publicações e links úteis
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Neoplasias por local
- Neoplasias
- Doenças Respiratórias
- Doenças pulmonares
- Neoplasias do Trato Respiratório
- Neoplasias Torácicas
- Neoplasias Pulmonares
- Carcinoma Broncogênico
- Neoplasias Brônquicas
- Carcinoma pulmonar de células não pequenas
- Compostos de enxofre
- Produtos químicos orgânicos
- Compostos heterocíclicos
- Compostos heterocíclicos, 2 anel
- Compostos heterocíclicos, anel fundido
- Terapêutica
- Amidas
- Indoles
- Sulfonamidas
- Sulfonas
- Vemurafenibe
- Terapia medicamentosa
- Atezolizumab
- Cobimetinibe
- Entrectinib
- Alectinib
- Pralsetinibe
Outros números de identificação do estudo
- ML41591
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano 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
Informações sobre medicamentos e dispositivos, documentos de estudo
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Estuda um produto de dispositivo regulamentado pela FDA dos EUA
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