En undersøgelse af flere terapier i biomarkør-udvalgte patienter med resektable stadier IB-III ikke-småcellet lungekræft (NAUTIKA1)
NAUTIKA1: Multicenter, fase II, neoadjuverende og adjuverende undersøgelse af multiple terapier i biomarkør-udvalgte patienter med resektable stadier IB-III ikke-småcellet lungekræft
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.
Studieoversigt
Status
Betingelser
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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California
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Los Angeles, California, Forenede Stater, 90095
- University of California Los Angeles - Jonsson Comprehensive Cancer Center
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Orange, California, Forenede Stater, 92868
- The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
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Sacramento, California, Forenede Stater, 95817
- UC Davis Comprehensive Cancer Center
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Connecticut
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New Haven, Connecticut, Forenede Stater, 06511
- Yale Cancer Center
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District of Columbia
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Washington D.C., District of Columbia, Forenede Stater, 20007
- MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
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Florida
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Tampa, Florida, Forenede Stater, 33612
- Moffitt Cancer Center
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Illinois
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Chicago, Illinois, Forenede Stater, 60611
- Northwestern University
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DeKalb, Illinois, Forenede Stater, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Geneva, Illinois, Forenede Stater, 60134
- Northwestern Medicine Cancer Center Delnor
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Warrenville, Illinois, Forenede Stater, 60555
- Northwestern Medicine Cancer Center Warrenville
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02215
- Dana-Farber Cancer Institute
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- University of Michigan
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Minnesota
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Rochester, Minnesota, Forenede Stater, 55905
- Mayo Clinic
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Missouri
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Columbia, Missouri, Forenede Stater, 65201
- Ellis Fischel Cancer Center
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St Louis, Missouri, Forenede Stater, 63108
- Siteman Cancer Center - Washington University Medical Campus
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New Hampshire
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Lebanon, New Hampshire, Forenede Stater, 03756
- Dartmouth Hitchcock Medical Center
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New York
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New York, New York, Forenede Stater, 10032
- Columbia University Medical Center
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New York, New York, Forenede Stater, 10065
- Memorial Sloan Kettering Cancer Center
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New York, New York, Forenede Stater, 10016
- Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
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Ohio
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Columbus, Ohio, Forenede Stater, 43210
- Ohio State University
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Pennsylvania
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Pittsburgh, Pennsylvania, Forenede Stater, 15212
- AHN Cancer Institute ? Allegheny General Hospital
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Tennessee
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Memphis, Tennessee, Forenede Stater, 38120
- Baptist Clinical Research Institute
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Texas
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Houston, Texas, Forenede Stater, 77030-4008
- University of Texas MD Anderson Cancer Center
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Virginia
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Fairfax, Virginia, Forenede Stater, 22031
- Virginia Cancer Specialists (Fairfax) - USOR
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
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Eksperimentel: 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).
Andre navne:
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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Eksperimentel: 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.
Andre navne:
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Eksperimentel: 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.
Andre navne:
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Eksperimentel: 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.
Andre navne:
Participants will receive oral cobimetinib daily.
Andre navne:
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Eksperimentel: 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.
Andre navne:
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Eksperimentel: 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.
Andre navne:
Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab. |
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Eksperimentel: 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.
Andre navne:
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs)
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
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Patologisk regression baseret på vægtet % vurdering af levedygtige tumorceller
Tidsramme: Efter kirurgisk resektion (ca. undersøgelse uge 8)
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Efter kirurgisk resektion (ca. undersøgelse uge 8)
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Investigator-vurderet Respons Objective Response Rate (ORR) pr. responsevalueringskriterier i solide tumorer version 1.1 (RECIST v1.1)
Tidsramme: Efter neoadjuverende behandling (efter ca. undersøgelsesuge 8)
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Efter neoadjuverende behandling (efter ca. undersøgelsesuge 8)
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Sygdomsfri overlevelse (DFS)
Tidsramme: Fra den første dato for ingen sygdom til lokalt eller fjernt tilbagefald eller død af enhver årsag, alt efter hvad der indtræffer først, til slutningen af undersøgelsen (op til 9 år)
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Fra den første dato for ingen sygdom til lokalt eller fjernt tilbagefald eller død af enhver årsag, alt efter hvad der indtræffer først, til slutningen af undersøgelsen (op til 9 år)
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Begivenhedsfri overlevelse (EFS)
Tidsramme: Fra første dosis af undersøgelsesbehandling til første dokumenterede sygdomsprogression pr. RECIST v1.1, eller lokalt eller fjernt sygdomstilbagefald som bestemt af investigator, eller død af enhver årsag, alt efter hvad der indtræffer først, til slutningen af undersøgelsen (op til 9 år)
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Fra første dosis af undersøgelsesbehandling til første dokumenterede sygdomsprogression pr. RECIST v1.1, eller lokalt eller fjernt sygdomstilbagefald som bestemt af investigator, eller død af enhver årsag, alt efter hvad der indtræffer først, til slutningen af undersøgelsen (op til 9 år)
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Samlet overlevelse (OS)
Tidsramme: Fra den første dosis af undersøgelsesmedicin til død af enhver årsag, til slutningen af undersøgelsen (op til 9 år)
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Fra den første dosis af undersøgelsesmedicin til død af enhver årsag, til slutningen af undersøgelsen (op til 9 år)
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Cirkulerende tumor DNA (ctDNA) Clearance Rate
Tidsramme: Før operation (før undersøgelse uge 8)
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Før operation (før undersøgelse uge 8)
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Percentage of Participants With AEs
Tidsramme: Up to 9 years
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Up to 9 years
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Proportion of Participants With MPR
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Samarbejdspartnere og efterforskere
Sponsor
Efterforskere
- Studieleder: Clinical Trials, Hoffmann-La Roche
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Neoplasmer efter sted
- Neoplasmer
- Luftvejssygdomme
- Lungesygdomme
- Neoplasmer i luftvejene
- Thoracale neoplasmer
- Lungeneoplasmer
- Karcinom, bronkogent
- Bronkiale neoplasmer
- Karcinom, ikke-småcellet lunge
- Svovlforbindelser
- Organiske kemikalier
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ring
- Terapeutik
- Amider
- Indoler
- Sulfonamider
- Sulfoner
- Vemurafenib
- Lægemiddelterapi
- atezolizumab
- Cobimetinib
- entrektinib
- alectinib
- PRALSETINIB
Andre undersøgelses-id-numre
- ML41591
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
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
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
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