Een studie van meerdere therapieën bij door biomarkers geselecteerde patiënten met reseceerbare stadia IB-III niet-kleincellige longkanker (NAUTIKA1)
NAUTIKA1: Multicenter, fase II, neoadjuvante en adjuvante studie van meerdere therapieën bij door biomarkers geselecteerde patiënten met resectabele stadia IB-III niet-kleincellige longkanker
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.
Studie Overzicht
Toestand
Conditie
Studietype
Inschrijving (Geschat)
Fase
- Fase 2
Contacten en locaties
Studie Locaties
-
-
California
-
Los Angeles, California, Verenigde Staten, 90095
- University of California Los Angeles - Jonsson Comprehensive Cancer Center
-
Orange, California, Verenigde Staten, 92868
- The Center for Cancer Prevention and Treatment at St.Joseph Hospital of Orange
-
Sacramento, California, Verenigde Staten, 95817
- UC Davis Comprehensive Cancer Center
-
-
Connecticut
-
New Haven, Connecticut, Verenigde Staten, 06511
- Yale Cancer Center
-
-
District of Columbia
-
Washington D.C., District of Columbia, Verenigde Staten, 20007
- MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
-
-
Florida
-
Tampa, Florida, Verenigde Staten, 33612
- Moffitt Cancer Center
-
-
Illinois
-
Chicago, Illinois, Verenigde Staten, 60611
- Northwestern University
-
DeKalb, Illinois, Verenigde Staten, 60115
- Northwestern Medicine Cancer Center Kishwaukee
-
Geneva, Illinois, Verenigde Staten, 60134
- Northwestern Medicine Cancer Center Delnor
-
Warrenville, Illinois, Verenigde Staten, 60555
- Northwestern Medicine Cancer Center Warrenville
-
-
Massachusetts
-
Boston, Massachusetts, Verenigde Staten, 02215
- Dana-Farber Cancer Institute
-
-
Michigan
-
Ann Arbor, Michigan, Verenigde Staten, 48109
- University of Michigan
-
-
Minnesota
-
Rochester, Minnesota, Verenigde Staten, 55905
- Mayo Clinic
-
-
Missouri
-
Columbia, Missouri, Verenigde Staten, 65201
- Ellis Fischel Cancer Center
-
St Louis, Missouri, Verenigde Staten, 63108
- Siteman Cancer Center - Washington University Medical Campus
-
-
New Hampshire
-
Lebanon, New Hampshire, Verenigde Staten, 03756
- Dartmouth Hitchcock Medical Center
-
-
New York
-
New York, New York, Verenigde Staten, 10032
- Columbia University Medical Center
-
New York, New York, Verenigde Staten, 10065
- Memorial Sloan Kettering Cancer Center
-
New York, New York, Verenigde Staten, 10016
- Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
-
-
Ohio
-
Columbus, Ohio, Verenigde Staten, 43210
- Ohio State University
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, Verenigde Staten, 15212
- AHN Cancer Institute ? Allegheny General Hospital
-
-
Tennessee
-
Memphis, Tennessee, Verenigde Staten, 38120
- Baptist Clinical Research Institute
-
-
Texas
-
Houston, Texas, Verenigde Staten, 77030-4008
- University of Texas MD Anderson Cancer Center
-
-
Virginia
-
Fairfax, Virginia, Verenigde Staten, 22031
- Virginia Cancer Specialists (Fairfax) - USOR
-
-
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Opdracht voor een enkele groep
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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).
Andere namen:
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. |
|
Experimenteel: 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.
Andere namen:
|
|
Experimenteel: 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.
Andere namen:
|
|
Experimenteel: 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.
Andere namen:
Participants will receive oral cobimetinib daily.
Andere namen:
|
|
Experimenteel: 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.
Andere namen:
|
|
Experimenteel: 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.
Andere namen:
Participants will receive SBRT given concurrently, starting with the first dose of atezolizumab. |
|
Experimenteel: 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.
Andere namen:
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
KRAS G12C Cohort: Percentage of Participants With 3-5 Grade Adverse Events (AEs)
Tijdsspanne: After surgical resection (approximately study Week 8)
|
After surgical resection (approximately study Week 8)
|
|
|
KRAS G12C Cohort: Percentage of Participants Without Delays of Surgery due to Treatment-related AEs as Reported by the Investigator
Tijdsspanne: After surgical resection (approximately study Week 8)
|
After surgical resection (approximately study Week 8)
|
|
|
Tyrosine Kinase Inhibitor (TKI) Cohort: Proportion of Participants With Major Pathologic Response (MPR)
Tijdsspanne: After surgical resection (approximately study Week 8)
|
MPR is defined as ≤ 10% residual viable tumor cells as scored by local pathologists. |
After surgical resection (approximately study Week 8)
|
|
Checkpoint Inhibitor (CPI) Cohort: Pathological Complete Response (pCR)
Tijdsspanne: After surgical resection (approximately study Week 8)
|
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)
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Pathologische regressie op basis van gewogen % levensvatbare tumorcelbeoordeling
Tijdsspanne: Na chirurgische resectie (ongeveer studieweek 8)
|
Na chirurgische resectie (ongeveer studieweek 8)
|
|
|
Door de onderzoeker beoordeelde respons Objectieve responsratio (ORR) per respons Evaluatiecriteria bij solide tumoren Versie 1.1 (RECIST v1.1)
Tijdsspanne: Na neoadjuvante behandeling (na ongeveer onderzoeksweek 8)
|
Na neoadjuvante behandeling (na ongeveer onderzoeksweek 8)
|
|
|
Ziektevrije overleving (DFS)
Tijdsspanne: Vanaf de eerste datum zonder ziekte tot lokaal of op afstand recidief of overlijden door welke oorzaak dan ook, afhankelijk van wat zich het eerst voordoet, tot het einde van het onderzoek (tot 9 jaar)
|
Vanaf de eerste datum zonder ziekte tot lokaal of op afstand recidief of overlijden door welke oorzaak dan ook, afhankelijk van wat zich het eerst voordoet, tot het einde van het onderzoek (tot 9 jaar)
|
|
|
Evenementvrij overleven (EFS)
Tijdsspanne: Vanaf de eerste dosis onderzoeksbehandeling tot de eerste gedocumenteerde ziekteprogressie volgens RECIST v1.1, of lokaal of op afstand terugkeren van de ziekte zoals bepaald door de onderzoeker, of overlijden door welke oorzaak dan ook, afhankelijk van wat zich het eerst voordoet, tot het einde van het onderzoek (tot 9 jaar)
|
Vanaf de eerste dosis onderzoeksbehandeling tot de eerste gedocumenteerde ziekteprogressie volgens RECIST v1.1, of lokaal of op afstand terugkeren van de ziekte zoals bepaald door de onderzoeker, of overlijden door welke oorzaak dan ook, afhankelijk van wat zich het eerst voordoet, tot het einde van het onderzoek (tot 9 jaar)
|
|
|
Algemene overleving (OS)
Tijdsspanne: Vanaf de eerste dosis onderzoeksmedicatie tot het overlijden door welke oorzaak dan ook, tot het einde van het onderzoek (tot 9 jaar)
|
Vanaf de eerste dosis onderzoeksmedicatie tot het overlijden door welke oorzaak dan ook, tot het einde van het onderzoek (tot 9 jaar)
|
|
|
Circulerend tumor-DNA (ctDNA) Opruimingspercentage
Tijdsspanne: Vóór de operatie (vóór studieweek 8)
|
Vóór de operatie (vóór studieweek 8)
|
|
|
Percentage of Participants With AEs
Tijdsspanne: Up to 9 years
|
Up to 9 years
|
|
|
Proportion of Participants With MPR
Tijdsspanne: After surgical resection (approximately study Week 8)
|
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)
|
|
Proportion of Participants With pCR
Tijdsspanne: After surgical resection (approximately study Week 8)
|
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)
|
|
Nodal Downstaging
Tijdsspanne: After surgical resection (approximately study Week 8)
|
Defined as percentage of participants with reduced stages in regional lymph nodes at surgery. |
After surgical resection (approximately study Week 8)
|
|
KRAS G12C Cohort: Plasma Concentration of Divarasib at Specified Timepoints
Tijdsspanne: 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);
|
|
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);
|
Medewerkers en onderzoekers
Sponsor
Onderzoekers
- Studie directeur: Clinical Trials, Hoffmann-La Roche
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start (Werkelijk)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Neoplasmata per site
- Neoplasmata
- Ziekten van de luchtwegen
- Longziekten
- Neoplasmata van de luchtwegen
- Thoracale neoplasmata
- Longneoplasmata
- Carcinoom, bronchogeen
- Bronchiale neoplasmata
- Carcinoom, niet-kleincellige long
- Zwavelverbindingen
- Organische chemicaliën
- Heterocyclische verbindingen
- Heterocyclische verbindingen, 2-ring
- Heterocyclische verbindingen, gefuseerd ring
- Therapeutica
- Amides
- Indolen
- Sulfonamides
- Sulfonen
- Vemurafenib
- Drugstherapie
- atezolizumab
- cobimetinib
- entrectinib
- alectinib
- pralsetinib
Andere studie-ID-nummers
- ML41591
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Beschrijving IPD-plan
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
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .