Undersøgelse af RMC-6291 i kombination med RMC-6236 hos deltagere med avancerede KRAS G12C mutante solide tumorer
Fase 1b, Multicenter, Open-Label, dosiseskalering og dosisudvidelsesundersøgelse af RMC-6291 i kombination med RMC-6236 hos deltagere med avancerede KRAS G12C mutante solide tumorer
This study is to evaluate the safety, tolerability, and PK profiles of Elironrasib and Daraxonrasib as monotherapies and combination therapy in patients with KRAS G12C-mutated solid tumors.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
This is an open-label, multicenter, Phase 1b/2 study evaluating elironrasib and daraxonrasib, administered as monotherapy and in combination, in patients with advanced KRAS G12C-mutated solid tumors to determine the maximum tolerated dose (MTD), identify the recommended Phase 2 dose and schedule (RP2DS), and preliminarily assess antitumor activity.
The study includes a Phase 1b dose escalation and expansion of combination therapy, followed by a Phase 2 evaluation of the selected RP2DS as monotherapy and combination therapy to further assess safety and antitumor activity.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Anslået)
Tilmelding
Fase
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Studiekontakt
Studiekontakt
- Navn: Revolution Medicines, Inc.
- Telefonnummer: 1-844-2-REVMED
- E-mail: medinfo@revmed.com
Studiesteder
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California
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Duarte, California, Forenede Stater, 91010
- Trukket tilbage
- City of Hope
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Orange, California, Forenede Stater, 92868
- Rekruttering
- UC IRVINE Health
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Sacramento, California, Forenede Stater, 95817
- Rekruttering
- UC Davis Comprehensive Cancer Center
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Stanford, California, Forenede Stater, 94305
- Rekruttering
- Stanford Cancer Institute
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Colorado
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Aurora, Colorado, Forenede Stater, 80045
- Rekruttering
- University of Colorado Cancer Center
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Florida
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Sarasota, Florida, Forenede Stater, 34232
- Rekruttering
- Florida Cancer Specialists
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Tampa, Florida, Forenede Stater, 33612
- Rekruttering
- Moffitt Cancer Center and Research Institute
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Indiana
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Indianapolis, Indiana, Forenede Stater, 46250
- Rekruttering
- Community Health Network
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Massachusetts
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Boston, Massachusetts, Forenede Stater, 02215
- Rekruttering
- Dana Farber Cancer Institute
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Michigan
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Detroit, Michigan, Forenede Stater, 48202
- Trukket tilbage
- Henry Ford Cancer
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Grand Rapids, Michigan, Forenede Stater, 49546
- Rekruttering
- START Midwest
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New York
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New York, New York, Forenede Stater, 10065
- Rekruttering
- Memorial Sloan Kettering Cancer Center
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New York, New York, Forenede Stater, 10032
- Rekruttering
- Columbia University
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New York, New York, Forenede Stater, 10032
- Rekruttering
- NYU Langone Health
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Oklahoma
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Oklahoma City, Oklahoma, Forenede Stater, 73104
- Rekruttering
- University of Oklahoma
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Pennsylvania
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Pittsburgh, Pennsylvania, Forenede Stater, 15212
- Rekruttering
- Allegheny Health Network
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Tennessee
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Nashville, Tennessee, Forenede Stater, 37203
- Rekruttering
- Sarah Cannon Research Institue
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Texas
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Dallas, Texas, Forenede Stater, 75230
- Afsluttet
- Mary Crowley Cancer Research
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Houston, Texas, Forenede Stater, 77030
- Rekruttering
- MD Anderson
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Irving, Texas, Forenede Stater, 75039
- Rekruttering
- NEXT Dallas
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San Antonio, Texas, Forenede Stater, 78229
- Rekruttering
- NEXT Oncology San Antonio
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San Antonio, Texas, Forenede Stater, 78229
- Rekruttering
- START Texas
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Virginia
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Fairfax, Virginia, Forenede Stater, 22031
- Rekruttering
- NEXT Oncology Virginia
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Angers, Frankrig, 49055
- Rekruttering
- West Cancer Institute
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Bordeaux, Frankrig, 33000
- Rekruttering
- Institut Bergonie
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Bron, Frankrig, 69500
- Rekruttering
- Hospital Louise Pradel
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Lille, Frankrig, 59000
- Rekruttering
- Oscar Lambret Center of Lillle
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Lyon, Frankrig, 69373
- Rekruttering
- Centre Leon Berard
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Montpellier, Frankrig, 34298
- Rekruttering
- Cancer Institute of Montpellier
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Nantes, Frankrig, 44093
- Rekruttering
- CHU Nantes
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Strasbourg, Frankrig, 67033
- Trukket tilbage
- Institute of Cancer of Strasbourg
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Amsterdam, Holland, 1066CX
- Rekruttering
- Netherlands Cancer Institute Antoni van Leeuwenhoek
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Ancona, Italien, 60126
- Rekruttering
- Department of Medical Oncology - Azienda Ospedaliero Uniersitaria delle Marche
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Aviano, Italien, 33081
- Rekruttering
- Centro Di Riferimento Oncologico
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Meldola, Italien, 47014
- Rekruttering
- Institute Romagnolo per lo Studio Tumori
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Milan, Italien, 20162
- Rekruttering
- Niguarda Cancer Center
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Naples, Italien, 80131
- Rekruttering
- Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale"
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Orbassano, Italien, 10043
- Rekruttering
- San Luigi Hospital
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Ravenna, Italien, 48121
- Rekruttering
- AUSL Romagna - S.M. delle Croci Hospital
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Veneto
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Verona, Veneto, Italien, 37134
- Rekruttering
- Centro Ricerche Cliniche di Verona Srl
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Puerto Rico
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San Juan, Puerto Rico, Puerto Rico, 00935
- Rekruttering
- Pan American Center for Oncology Trials
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Barcelona, Spanien, 08023
- Rekruttering
- START Barcelona - Hospital HM Nou Delfos
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Barcelona, Spanien, 08908
- Rekruttering
- Institut Catala d'Oncologia Hospital
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Madrid, Spanien, 28041
- Rekruttering
- Hospital Universitario 12 de Octubre
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Madrid, Spanien, 28027
- Rekruttering
- University Clinic of Navarra
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Madrid, Spanien, 28033
- Rekruttering
- Fundacion MD Anderson Cancer Center
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Madrid, Spanien, 28223
- Rekruttering
- NEXT Oncology - Quirónsalud Madrid University Hospital
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Madrid, Spanien, 28040
- Rekruttering
- START Madrid
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Pamplona, Spanien, 31008
- Rekruttering
- University Clinic of Navarra
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Seville, Spanien, 41009
- Rekruttering
- Hospital Universitario Virgen Macarena
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Valencia, Spanien, 46026
- Rekruttering
- La Fe University and Polytechnic Hospital
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Zaragoza, Spanien, 50009
- Rekruttering
- Hospital Universitario Miguel Servet
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Cologne, Tyskland, 80937
- Rekruttering
- Universitäts Klinikum Köln
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Esslingen am Neckar, Tyskland, 73730
- Rekruttering
- Klinikum Esslingen GmbH
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Moers, Tyskland, 47441
- Rekruttering
- Krankenhaus Bethanien Moers
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Nuremberg, Tyskland, 90419
- Rekruttering
- Klinkum Nurnberg Paracelsus Medical Unviersity
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
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18 years of age
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Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy
- Phase 1b Dose Escalation: solid tumors, previously treated
- Phase 1b Dose Expansion and Phase 2:
i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors ii. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.
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ECOG performance status 0 or 1
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Adequate organ function
Exclusion Criteria:
- Primary central nervous system (CNS) tumors
- Active brain metastases
- Known impairment of GI function that would alter the absorption
- Major surgical procedures within 28 days or non-study related minor procedures within 7 days of treatment
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Eksperimentel: Elironrasib Monotherapy
Phase 2 only |
oral tablets
Andre navne:
|
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Eksperimentel: Daraxonrasib Monotherapy
Phase 2 only |
oral tablets
Andre navne:
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Eksperimentel: Daraxonrasib + Elironrasib Combination
Phase 1b and 2 |
oral tablets
Andre navne:
oral tablets
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Number of patients with adverse events (AEs) in Phase 1b
Tidsramme: Up to approximately 3 years
|
Incidence and severity of treatment-emergent AEs and serious AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5 |
Up to approximately 3 years
|
|
Changes in vital signs in Phase 1b
Tidsramme: Up to approximately 3 years
|
Number of patients with clinically significant changes in vital signs |
Up to approximately 3 years
|
|
Changes in clinical laboratory test values in Phase 1b
Tidsramme: Up to approximately 3 years
|
Number of patients with clinically significant changes in clinical laboratory test values |
Up to approximately 3 years
|
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Dose Limiting Toxicities in Phase 1b
Tidsramme: 21 days
|
Number of participants with dose limiting toxicities |
21 days
|
|
Changes in ECGs in Phase 1b
Tidsramme: Up to approximately 3 years
|
Number of patients with clinically significant changes in ECGs |
Up to approximately 3 years
|
|
Overall Response Rate (ORR) in Phase 2
Tidsramme: Up to approximately 3 years
|
Overall response rate per RECIST v1.1 as assessed by blinded independent central review (BICR) |
Up to approximately 3 years
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Maximum Observed Blood Concentration of Elironrasib and Daraxonrasib
Tidsramme: up to 21 weeks
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Cmax |
up to 21 weeks
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Time to Reach Maximum Blood Concentration of Elironrasib and Daraxonrasib
Tidsramme: up to 21 weeks
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Tmax |
up to 21 weeks
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Area Under Blood Concentration Time Curve of Elironrasib and Daraxonrasib
Tidsramme: up to 21 weeks
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AUC |
up to 21 weeks
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Elimination Half-Life of Elironrasib and Daraxonrasib
Tidsramme: up to 21 weeks
|
t1/2 |
up to 21 weeks
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Ratio of accumulation of Elironrasib and Daraxonrasib from a single dose to steady state with repeated dosing
Tidsramme: up to 21 weeks
|
accumulation ratio |
up to 21 weeks
|
|
Overall Response Rate (ORR) in Phase 1b
Tidsramme: Up to approximately 3 years
|
Overall response rate per RECIST v1.1 |
Up to approximately 3 years
|
|
Duration of Response (DOR)
Tidsramme: Up to approximately 3 years
|
Duration of response per RECIST v1.1 |
Up to approximately 3 years
|
|
Disease Control Rate in Phase 1b
Tidsramme: Up to approximately 3 years
|
Disease Control rate per RECIST v1.1 |
Up to approximately 3 years
|
|
Time to Response (TTR) in Phase 1b
Tidsramme: Up to approximately 3 years
|
Time to response per RECIST v1.1 |
Up to approximately 3 years
|
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Progression-Free Survival (PFS)
Tidsramme: Up to approximately 3 years
|
Progression-free survival per RECIST v1.1 |
Up to approximately 3 years
|
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Number of patients with AEs in Phase 2
Tidsramme: Up to approximately 3 years
|
Incidence and severity of treatment-emergent AEs and serious AEs as assessed by CTCAE v5 |
Up to approximately 3 years
|
|
Changes in vital signs in Phase 2
Tidsramme: Up to approximately 3 years
|
Number of patients with clinically significant changes in vital signs |
Up to approximately 3 years
|
|
Changes in clinical laboratory values in Phase 2
Tidsramme: Up to approximately 3 years
|
Number of patients with clinically significant changes in clinical laboratory test values |
Up to approximately 3 years
|
|
Overall Survival (OS) in Phase 2
Tidsramme: Up to approximately 3 years
|
OS is defined as time from enrollment until death from any cause |
Up to approximately 3 years
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Efterforskere
Efterforskere
- Studieleder: Revolution Medicines, Inc., Revolution Medicines, Inc.
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Anslået)
Primær færdiggørelse
Studieafslutning (Anslået)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Nøgleord
- Lungekræft
- NSCLC
- Neoplasmer
- Mavekræft
- Målrettet terapi
- Kræft i bugspytkirtlen
- Kolorektal cancer
- Livmoderhalskræft
- KRAS mutation
- STK11/LKB1
- KEAP1
- Endometriecancer
- Metastatisk kræft
- Spiserørskræft
- Endetarmskræft
- Tyktarmskræft
- Ikke-småcellet lungekræft
- Thoracale neoplasmer
- KRAS
- CRC
- PDAC
- Ampulær kræft
- Intestinale neoplasmer
- Gastrointestinale neoplasmer
- Gynækologisk kræft
- Colon neoplasmer
- Lungeneoplasmer
- Lungesygdom
- RMC-6291
- KRASG12C
- Karcinom, ikke-småcellet lunge
- Blindtarmskræft
- Karcinom, bugspytkirtelduktal
- Neoplasmer efter sted
- Luftvejssygdomme
- Bronchiale neoplasmer
- RAS (ON)
- KRASG12C (ON)
- Neoplasmer i luftvejene
- RMC-6236
- Elironrasib
- Daraxonrasib
Yderligere relevante MeSH-vilkår
- Urogenitale sygdomme
- Genitale sygdomme
- Sygdomme i det endokrine system
- Patologiske processer
- Urogenitale neoplasmer
- Urogenitale sygdomme hos kvinder
- Kvinders urogenitale sygdomme og graviditetskomplikationer
- Tarmsygdomme
- Neoplasmer efter histologisk type
- Neoplasmer i fordøjelsessystemet
- Sygdomme i fordøjelsessystemet
- Gastrointestinale sygdomme
- Mavesygdomme
- Endetarmssygdomme
- Livmodersygdomme
- Kønssygdomme, kvindelige
- Bronchiale sygdomme
- Neoplasmer i endokrine kirtler
- Neoplasmer i hoved og hals
- Pancreassygdomme
- Neoplasmer, kirtel og epitel
- Adenocarcinom
- Tyktarmssygdomme
- Neoplastiske processer
- Esophageale sygdomme
- Ovariesygdomme
- Adnexale sygdomme
- Genitale neoplasmer, kvindelige
- Gonadale lidelser
- Karcinom
- Karcinom, bronkogent
- Uterine neoplasmer
- Neoplasmer, duktale, lobulære og medullære
- Cecal neoplasmer
- Cecale sygdomme
- Carcinom, Ductal
- Patologiske tilstande, tegn og symptomer
- Neoplasmer
- Neoplasmer i maven
- Rektale neoplasmer
- Lungesygdomme
- Lungeneoplasmer
- Kolorektale neoplasmer
- Colon neoplasmer
- Esophageale neoplasmer
- Ovariale neoplasmer
- Neoplasma Metastase
- Bugspytkirtel neoplasmer
- Gastrointestinale neoplasmer
- Karcinom, ikke-småcellet lunge
- Intestinale neoplasmer
- Endometriale neoplasmer
- Luftvejssygdomme
- Thoracale neoplasmer
- Neoplasmer i luftvejene
- Neoplasmer efter sted
- Appendiceale neoplasmer
- Karcinom, bugspytkirtelduktal
- Bronkiale neoplasmer
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- RMC-6291-101
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
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