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Undersøgelse af de molekylære egenskaber hos postmenopausale kvinder med HR+ HER2-negativ aBC ved førstelinjebehandling med Ribociclib og Letrozol og, hos patienter med en PIK3CA-mutation, på andenlinjebehandling med Alpelisib Plus Fulvestrant (BioItaLEE)

12. juni 2026 opdateret af: Novartis Pharmaceuticals

En fase IIIb, åben, lokal, multicenter undersøgelse af de molekylære egenskaber hos postmenopausale kvinder med hormonreceptorpositiv (HR+) HER2-negativ avanceret brystkræft på førstelinjebehandling med Ribociclib Plus Letrozol og hos patienter med en PIK3CA-mutation , om andenlinjebehandling med Alpelisib Plus Fulvestrant (BioItaLEE)

Formålet med dette kliniske forsøg er at studere de molekylære egenskaber hos postmenopausale kvinder med hormonreceptor-positiv (HR+) HER2-negativ fremskreden brystkræft i førstelinjebehandling med ribociclib og letrozol og, hos patienter med en PIK3CA-mutation, på anden. -linjebehandling med alpelisib plus fulvestrant

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

Hovedformålet med denne lokale, multicenterundersøgelse er at undersøge genetiske ændringer og genekspressionsændringer i tumor før og efter progression på ribociclib, under kernefasen og derefter før og efter progression på alpelisib og dermed identificere mutationsmønstre, hvordan de udvikler sig, og deres sammenhæng med CDK4/6-hæmning og resultater såsom vedvarende respons eller tidlig progression. Undersøgelsen har også til formål at evaluere farmakogenomik og dens sammenhæng med uønskede hændelser (hyppighed og sværhedsgrad), lægemiddel-interaktioner og kliniske resultater.

Endelig vil undersøgelsen også generere yderligere langsigtede sikkerheds- og effektdata i denne specifikke italienske befolkning.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

287

Fase

  • Fase 3

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Italien
      • Naples, Italien, 80131
        • Novartis Investigative Site
      • Naples, Italien, 80138
        • Novartis Investigative Site
    • AL
      • Casale Monferrato, AL, Italien, 15033
        • Novartis Investigative Site
    • BA
      • Bari, BA, Italien, 70124
        • Novartis Investigative Site
    • BG
      • Bergamo, BG, Italien, 24127
        • Novartis Investigative Site
    • BN
      • Benevento, BN, Italien, 82100
        • Novartis Investigative Site
    • BO
      • Bologna, BO, Italien, 40138
        • Novartis Investigative Site
    • BR
      • Brindisi, BR, Italien, 72100
        • Novartis Investigative Site
    • BS
      • Brescia, BS, Italien, 25123
        • Novartis Investigative Site
    • CR
      • Cremona, CR, Italien, 26100
        • Novartis Investigative Site
    • CT
      • Catania, CT, Italien, 95124
        • Novartis Investigative Site
      • Catania, CT, Italien, 95123
        • Novartis Investigative Site
    • FE
      • Cona, FE, Italien, 44100
        • Novartis Investigative Site
    • FG
      • San Giovanni Rotondo, FG, Italien, 71013
        • Novartis Investigative Site
    • GE
      • Genova, GE, Italien, 16132
        • Novartis Investigative Site
    • LI
      • Livorno, LI, Italien, 57124
        • Novartis Investigative Site
    • MB
      • Monza, MB, Italien, 20900
        • Novartis Investigative Site
    • MC
      • Province of Macerata, MC, Italien, 62100
        • Novartis Investigative Site
    • ME
      • Messina, ME, Italien, 98158
        • Novartis Investigative Site
    • MI
      • Milan, MI, Italien, 20133
        • Novartis Investigative Site
      • Milan, MI, Italien, 20141
        • Novartis Investigative Site
      • Milan, MI, Italien, 20132
        • Novartis Investigative Site
      • Rozzano, MI, Italien, 20089
        • Novartis Investigative Site
    • NU
      • Nuoro, NU, Italien, 08100
        • Novartis Investigative Site
    • PA
      • Palermo, PA, Italien, 90127
        • Novartis Investigative Site
      • Palermo, PA, Italien, 90146
        • Novartis Investigative Site
    • PD
      • Padova, PD, Italien, 35100
        • Novartis Investigative Site
    • PG
      • Perugia, PG, Italien, 06129
        • Novartis Investigative Site
    • PI
      • Pisa, PI, Italien, 56126
        • Novartis Investigative Site
    • PN
      • Aviano, PN, Italien, 33081
        • Novartis Investigative Site
    • PO
      • Prato, PO, Italien, 59100
        • Novartis Investigative Site
    • PU
      • Fano, PU, Italien, 61032
        • Novartis Investigative Site
    • RA
      • Faenza, RA, Italien, 48018
        • Novartis Investigative Site
    • RM
      • Roma, RM, Italien, 00168
        • Novartis Investigative Site
      • Roma, RM, Italien, 00128
        • Novartis Investigative Site
      • Roma, RM, Italien, 00189
        • Novartis Investigative Site
    • SA
      • Salerno, SA, Italien, 84131
        • Novartis Investigative Site
    • TO
      • Candiolo, TO, Italien, 10060
        • Novartis Investigative Site
      • Torino, TO, Italien, 10128
        • Novartis Investigative Site
    • UD
      • Udine, UD, Italien, 33100
        • Novartis Investigative Site
    • VR
      • Negrar, VR, Italien, 37024
        • Novartis Investigative Site

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Beskrivelse

KERNEFASE Inklusionskriterier:

  • Patienten har en fremskreden (lokoregionalt tilbagevendende eller metastatisk) brystkræft i førstelinjebehandling (behandlingsnaiv for den fremskredne indstilling).
  • Patienten er i postmenopause, defineret ved en af ​​følgende:
  • Tidligere bilateral ooforektomi
  • Alder ≥60
  • Alder <60 og amenoré i 12 eller flere måneder (i fravær af kemoterapi, tamoxifen, toremifen eller ovariesuppression) og FSH og østradiol i det postmenopausale område pr. lokalt normalområde
  • Patienten har en histologisk og/eller cytologisk bekræftet diagnose af østrogenreceptorpositiv og/eller progesteronreceptorpositiv brystkræft af lokalt laboratorium.
  • Patienten har en HER2-negativ brystkræft defineret som en negativ in situ hybridiseringstest eller en IHC-status på 0, 1+ eller 2+. Hvis IHC er 2+, kræves en negativ in situ hybridiseringstest (FISH, CISH eller SISH) ved lokal laboratorietest.
  • Patienten er villig til at gennemgå blod- og tumorprøvetagning til de biologiske vurderinger/mål som planlagt i protokollen.

KERNEFASE Eksklusionskriterier:

  • Patient, der tidligere har modtaget behandling med en hvilken som helst CDK4/6-hæmmer.
  • Patient, som tidligere har modtaget systemisk hormonbehandling eller kemoterapi for fremskreden brystkræft.

Bemærk:

Patienter, der modtog neo/adjuverende behandling for brystkræft, er berettigede. Hvis den tidligere neo/adjuverende behandling omfattede letrozol eller anastrozol, skal det sygdomsfrie interval være større end 12 måneder fra afslutningen af ​​behandlingen og indtil studiestart.

• Patienter, der har modtaget ≤ 28 dage med letrozol eller anastrozol for fremskreden sygdom før inklusion i dette forsøg, er kvalificerede.

- Patienten bruger i øjeblikket anden kræftbehandling. Andre protokoldefinerede inklusions-/udelukkelseskriterier kan være gældende.

UDVIDELSESFASE Inklusionskriterier:

  • Patienten er blevet afbrudt (enhver tilladt grund) fra behandling med ribociclib + letrozol i kernefasen og anses for egnet til behandling med alpelisib + fulvestrant i anden linje. Ribociclib + letrozol skal være det sidste behandlingsregime før alpelisib + fulvestrant.
  • Patienten har PIK3CA mutation som bestemt i tumorvæv og/eller plasma af et Novartis udpeget laboratorium. Resultater af vævsprøver opnået under kernefasen (screening eller EOT) er acceptable

UDVIDELSESFASE Eksklusionskriterier:

  • Patienten har tidligere modtaget behandling med PI3K-hæmmere.
  • Patienten bruger samtidig anden kræftbehandling. Ribociclib og letrozol anvendt i kernefasen skal seponeres mindst 7 dage før dag ét i forlængelsesundersøgelsesbehandlingen.

Alle lægemidler med overlappende toksicitet skal seponeres inden for 7 dage, og AE skal opløses til NCI CTCAE v4.03 Grade ≤1 før undersøgelsesbehandling. Undtagelse fra dette kriterium: patienter med enhver grad af alopeci får lov til at deltage i undersøgelsen.

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: ribociclib+letrozol
Ribociclib oral (3 uger on/1 uge fri) i kombination med oral letrozol én gang daglig: 600 mg tabletter ribociclib QD + 2,5 mg tabletter letrozol QD
Medicin: Ribociclib
Ribociclib oral (3 uger on/1 uge fri) i kombination med oral letrozol én gang daglig: 600 mg tabletter ribociclib QD + 2,5 mg tabletter letrozol QD
Andre navne:
  • LEE011
Medicin: Letrozol
Ribociclib oral (3 uger on/1 uge fri) i kombination med oral letrozol én gang daglig: 600 mg tabletter ribociclib QD + 2,5 mg tabletter letrozol QD
Eksperimentel: alpelisib+fulvestrant
Alpelisib 300 mg oral daglig på et kontinuerligt doseringsskema i kombination med fulvestrant 500 mg intramuskulært på dag 1 og 15 i cyklus 1 og på dag 1 i hver cyklus derefter i en 28 dages cyklus
Medicin: Alpelisib
Alpelisib 300 mg oral daglig på et kontinuerligt doseringsskema i kombination med fulvestrant 500 mg intramuskulært på dag 1 og 15 i cyklus 1 og på dag 1 i hver cyklus derefter i en 28 dages cyklus
Andre navne:
  • BYL719
Medicin: Fulvestrant
Alpelisib 300 mg oral daglig på et kontinuerligt doseringsskema i kombination med fulvestrant 500 mg intramuskulært på dag 1 og 15 i cyklus 1 og på dag 1 i hver cyklus derefter i en 28 dages cyklus

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Progression-Free Survival (PFS) by Cycle 1 Day 15 Complete Mutational Dynamic Change
Tidsramme: Up to approximately 5.7 years
PFS: Time (months) from start of the study treatment to first documented progression or death due to any cause, whichever came first. Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms [SNPs] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( [SNPs] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
Up to approximately 5.7 years
Number of Participants With Progression-Free Survival (PFS) Events by Cycle 1 Day 15 Complete Mutational Dynamic Change
Tidsramme: Up to approximately 5.7 years
Kaplan-Meier estimates. Persistent Wild Type: Wild Type (or single nucleotide polymorphisms [SNPs] only) at screening without hotspot mutations at any later assessment. Confirmed cleared: Mutated, with 100% decrease in target mutation variant allele frequency (VAF) at C1D15 or at C2D1 also observed at FI. Unconfirmed cleared: Mutated that cleared or at C1D15 or at C2D1 that were not cleared at FI. Late cleared: Mutated without 100% decrease in target mutation VAF at C1D15 and at C2D1 with 100% decrease in target mutation VAF at FI. New mutated: Wild Type ( [SNPs] only) at screening with hotspot mutations at C1D15 or C2D1. Late mutated: Wild Type patients (or SNPs only) at screening without hotspot mutations at C1D15 and C2D1 with hotspot mutations at FI. Confirmed mutated: Mutated without 100% decrease in target mutation VAF at any later assessment.
Up to approximately 5.7 years
Number of Participants With Hotspot Mutated Genes by Scheduled Timepoint
Tidsramme: Up to approximately 5.7 years
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. The data row labels below refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Up to approximately 5.7 years
Percent Change From Screening in Target Mutation Variant Allele Frequency (VAF)
Tidsramme: Up to approximately 5.7 years
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Up to approximately 5.7 years
Number of Participants With Partial Response (PR) in the Extension Phase
Tidsramme: Up to approximately 1.6 years
PR was assessed per Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1, criteria and was defined as at least a 30% decrease in the sum of diameter of all target lesions, taking as reference the screening sum of diameters.
Up to approximately 1.6 years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Percent Change From Screening in Thymidine Kinase 1 (TK1) Serum Level
Tidsramme: Up to approximately 5.7 years
Up to approximately 5.7 years
Number of Long Responder Participants With Hotspot Mutated Genes by Scheduled Timepoint
Tidsramme: Up to approximately 5.7 years
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Up to approximately 5.7 years
Number of Early Progressor Participants With Hotspot Mutated Genes by Scheduled Timepoint
Tidsramme: Up to approximately 5.7 years
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Up to approximately 5.7 years
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Long Responders
Tidsramme: Up to approximately 5.7 years
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Up to approximately 5.7 years
Percent Change From Screening in Target Mutation Molecular Frequency (VAF) for Early Progressors
Tidsramme: Up to approximately 5.7 years
The target mutation was defined as the hotspot mutation with the highest molecular frequency observed at screening excluding single nucleotide polymorphisms (SNPs, i.e., hotspot mutations observed at all timepoints with a minimum molecular frequency value of 30% and a variation coefficient greater than 0.15). The molecular frequency of target mutation at performed assessments during which the target mutation was not detected was assumed to be equal to 0%.
Up to approximately 5.7 years
Number of Screening Hotspot Mutations Per De Novo Patient in Liquid Biopsy Samples and Tissue Samples
Tidsramme: Up to approximately 5.7 years
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Up to approximately 5.7 years
Number of Screening Hotspot Mutations Per Recurrent Patient in Liquid Biopsy Samples and Tissue Samples
Tidsramme: Up to approximately 5.7 years
Hotspot mutational analysis on liquid biopsy was performed on the 39 genes belonging to the BioItaLEE custom panel. Data row labels refer to the number of hotspot-mutated genes at each timepoint. Each cycle was 28 days. PD = progressive disease.
Up to approximately 5.7 years
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at Screening
Tidsramme: Up to approximately 5.7 years
Results data refer to the total number of evaluations (i.e. the number of participants in the biomarker analysis set with both valid baseline liquid biopsy and tissue sample multiplied by 39 considered genes).
Up to approximately 5.7 years
Overall Number of Evaluations of Hotspot Mutations and Non-hotspot Mutations Present in Both Liquid Biopsies and Tissue Samples at End of Treatment
Tidsramme: Up to approximately 5.7 years
Results data refer to the total number of evaluations (i.e. the number of participants in the biomarker analysis set with both valid baseline liquid biopsy and tissue sample multiplied by 39 considered genes).
Up to approximately 5.7 years
Time to Progression (TTP)
Tidsramme: Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Time to progression (TTP) was defined as time from date of start of treatment to the date of event defined as the first documented progression or death due to underlying cancer.
Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Percentage of Participants With Best Overall Response Rate of Complete Response (CR) or Partial Response (PR)
Tidsramme: Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
ORR was defined as the percentage of participants with a best overall response defined as complete response (CR) or partial response (PR): (CR+PR) per Response Evaluation Criteria in Solid Tumors (RECIST), v. 1.1. CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Percentage of Participants With Clinical Benefit Rate
Tidsramme: Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Clinical benefit rate (CBR) was defined as the percentage of participants with a best overall response of complete response (CR), or partial response (PR) or an overall lesion response of stable disease (SD), lasting as per local review, for a duration of at least 24 weeks. Per RECIST v. 1.1, CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum longest diameter since the treatment started.
Core phase: up to approximately 5.7 years. Extension phase: up to approximately 1.6 years
Change From Baseline Tumor Mutational Burden (TMB) to Progression of Disease During the Core and Extension Phases
Tidsramme: Up to approximately 5.7 years
Up to approximately 5.7 years
Change From Baseline Tumor Microenvironment Parameters to Progression of Disease During the Core and Extension Phases
Tidsramme: Up to approximately 5.7 years
Up to approximately 5.7 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Novartis Pharmaceuticals

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

2. februar 2018

Primær færdiggørelse (Faktiske)

11. december 2023

Studieafslutning (Faktiske)

11. december 2023

Datoer for studieregistrering

Først indsendt

29. januar 2018

Først indsendt, der opfyldte QC-kriterier

13. februar 2018

Først opslået (Faktiske)

20. februar 2018

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

10. juli 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

12. juni 2026

Sidst verificeret

1. juni 2026

Mere information

Begreber relateret til denne undersøgelse

Nøgleord

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • CLEE011AIT01
  • 2017-004176-62 (EudraCT nummer)

Plan for individuelle deltagerdata (IPD)

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