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Studio che valuta l'efficacia e la sicurezza del trattamento con Alpelisib Plus Fulvestrant in uomini giapponesi e donne in postmenopausa con carcinoma mammario avanzato

17 settembre 2026 aggiornato da: Novartis Pharmaceuticals

Uno studio di Fase II in aperto, in due parti, multicentrico su BYL719 (Alpelisib) in combinazione con Fulvestrant per uomini e donne in postmenopausa con carcinoma mammario avanzato positivo al recettore dell'ormone della mutazione PIK3CA (HR), HER2-negativo, che è progredito durante o Dopo il trattamento con inibitore dell'aromatasi (AI) in Giappone

The purpose of this study is to assess the safety and efficacy of alpelisib plus fulvestrant in men and postmenopausal women with hormone receptor (HR) positive, human epidermal growth factor 2 (HER2)-negative, advanced breast cancer harboring a PIK3CA mutation in Japan, whose disease has progressed on or after aromatase inhibitor (AI) treatment regardless of prior CDK4/6 inhibitor use.

Panoramica dello studio

Stato

Attivo, non reclutante

Condizioni

Intervento / Trattamento

Descrizione dettagliata

This is a Phase II open-label, 2-Part, multi-center study in Japan. The study will be conducted in two parts: Part 1 (Cohort 1) includes participants regardless of prior CDK4/6 inhibitor use and is designed to determine the recommended dose (RD), evaluate the tolerability and safety of alpelisib in combination with fulvestrant. Part 2 consists of 2 cohorts (the CDK4/6 inhibitor naive participants are in Cohort 2 and the CDK4/6 inhibitor pre-treated participants are in Cohort 3) which are designed to assess the efficacy and safety of alpelisib in combination with fulvestrant, will start once the RD of alpelisib is established.

Participants will be treated until disease progression, unacceptable toxicity, death or discontinuation from the study treatment for any other reason and will be followed for survival regardless of treatment discontinuation reason (except if consent is withdrawn or participant is lost to follow up).

Tipo di studio

Interventistico

Iscrizione (Effettivo)

24

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Giappone
      • Niigata, Giappone, 951-8566
        • Novartis Investigative Site
    • Aichi-ken
      • Nagoya, Aichi-ken, Giappone, 4668560
        • Novartis Investigative Site
      • Nagoya, Aichi-ken, Giappone, 4678602
        • Novartis Investigative Site
      • Nagoya, Aichi-ken, Giappone, 4648681
        • Novartis Investigative Site
    • Chiba
      • Kashiwa, Chiba, Giappone, 2778577
        • Novartis Investigative Site
    • Kanagawa
      • Isehara, Kanagawa, Giappone, 2591193
        • Novartis Investigative Site
      • Yokohama, Kanagawa, Giappone, 2418515
        • Novartis Investigative Site
    • Kumamoto
      • Kumamoto, Kumamoto, Giappone, 8608556
        • Novartis Investigative Site
    • Miyagi
      • Sendai, Miyagi, Giappone, 9808574
        • Novartis Investigative Site
    • Osaka
      • Osaka, Osaka, Giappone, 5418567
        • Novartis Investigative Site
      • Osaka, Osaka, Giappone, 5400006
        • Novartis Investigative Site
      • Suita, Osaka, Giappone, 5650871
        • Novartis Investigative Site
    • Tokyo
      • Bunkyo Ku, Tokyo, Giappone, 1138677
        • Novartis Investigative Site
      • Koto Ku, Tokyo, Giappone, 1358550
        • Novartis Investigative Site
      • Meguro-ku, Tokyo, Giappone, 1528902
        • Novartis Investigative Site

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

Da 18 anni a 100 anni (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Japanese man or postmenopausal woman
  • Participant has adequate tumor tissue for the analysis of PIK3CA mutational status by a Novartis designated laboratory.
  • Participant has identified PIK3CA mutation (as determined by a Novartis designated laboratory)
  • Participant has a histologically and/or cytologically confirmed diagnosis of ER+ and/or PgR+ breast cancer by local laboratory
  • Participant has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH or SISH) test is required by local laboratory testing
  • Participant has measurable disease, i.e., at least one measurable lesion as per RECIST 1.1
  • Participant has advanced breast cancer
  • Participant has ECOG performance status 0 or 1

Exclusion Criteria:

  • Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy per the investigator's best judgment
  • Participant has received prior treatment;
  • with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR or AKT inhibitor for Cohort 1 and 3
  • with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, any PI3K, mTOR, AKT inhibitor or CDK 4/6 inhibitor for Cohort 2
  • Participant has a known hypersensitivity to alpelisib or fulvestrant, or to any of the excipients of alpelisib or fulvestrant
  • Participant with inflammatory breast cancer at screening
  • Participant is concurrently using other anti-cancer therapy
  • Participant has had surgery within 14 days prior to starting study drug or has not recovered from major side effects
  • Participant with an established diagnosis at screening of diabetes mellitus type I or not controlled type II (based on FPG and HbA1c)
  • Participant has currently documented pneumonitis /interstitial lung disease
  • History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
  • Participant with unresolved osteonecrosis of the jaw
  • Participant has a history of severe cutaneous reactions

Other protocol-defined inclusion/exclusion criteria may apply

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Non randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Cohort 1:CDK4/6 inhibitor naive or pre-treated (Part 1)

Participants regardless of prior CDK4/6 inhibitor will be treated at escalating doses (200 mg, 250 mg and 300 mg, orally) of BYL719 in combination with Fulvestrant (500 mg, intramuscular).
Droga: Alpelisib

[Part 1] Alpelisib administered at 200 mg (DL 1), 250 mg (DL 2) or 300mg (DL 3) orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

If DL 1 is tolerated, the alpelisib doses of 250 mg will be investigated. If DL 2 is tolerated, the alpelisib doses of 300 mg will be investigated.

[Part 2] In the Part 2, participants will be enrolled into Cohort 2 (CDK4/6 inhibitor naive) and Cohort 3 (CDK4/6 inhibitor pre-treated) in parallel and alpelisib will be administered at the recommended dose identified in Part 1.

Altri nomi:
  • BYL719
Droga: Fulvestrant

Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Altri nomi:
  • Faslodex
Sperimentale: Cohort 2: CDK4/6 inhibitor naive (Part 2)

Participants who are CDK4/6 inhibitor naive will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).
Droga: Alpelisib

[Part 1] Alpelisib administered at 200 mg (DL 1), 250 mg (DL 2) or 300mg (DL 3) orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

If DL 1 is tolerated, the alpelisib doses of 250 mg will be investigated. If DL 2 is tolerated, the alpelisib doses of 300 mg will be investigated.

[Part 2] In the Part 2, participants will be enrolled into Cohort 2 (CDK4/6 inhibitor naive) and Cohort 3 (CDK4/6 inhibitor pre-treated) in parallel and alpelisib will be administered at the recommended dose identified in Part 1.

Altri nomi:
  • BYL719
Droga: Fulvestrant

Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Altri nomi:
  • Faslodex
Sperimentale: Cohort 3: CDK4/6 inhibitor pre-treated (Part 2)

Participants who are CDK4/6 inhibitor pre-treated will be treated with BYL719 at the recommended dose identified in Part 1 in combination with Fulvestrant (500 mg, intramuscular).
Droga: Alpelisib

[Part 1] Alpelisib administered at 200 mg (DL 1), 250 mg (DL 2) or 300mg (DL 3) orally once daily on a continuous dosing schedule starting on Cycle 1 Day 1 in a 28 day cycle.

If DL 1 is tolerated, the alpelisib doses of 250 mg will be investigated. If DL 2 is tolerated, the alpelisib doses of 300 mg will be investigated.

[Part 2] In the Part 2, participants will be enrolled into Cohort 2 (CDK4/6 inhibitor naive) and Cohort 3 (CDK4/6 inhibitor pre-treated) in parallel and alpelisib will be administered at the recommended dose identified in Part 1.

Altri nomi:
  • BYL719
Droga: Fulvestrant

Fulvestrant is administered at a dose of 500 mg intramuscular on Cycle 1 Day 1, Day 15, and Day 1 of every cycle thereafter (where a cycle is 28 days).

Altri nomi:
  • Faslodex

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
[Part 1] The incidence of Dose Limiting Toxicities (DLTs) of alpelisib in combination with fulvestrant
Lasso di tempo: From Cycle 1 Day 1 to Cycle 2 Day 28 (Cycle = 28 days)

A DLT is defined as an AE or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 2 cycles (the first 56 days) of treatment with alpelisib in combination with fulvestrant and meets any of the criteria specified in the protocol .
From Cycle 1 Day 1 to Cycle 2 Day 28 (Cycle = 28 days)
[Part 2] Overall Response Rate (ORR) in CDK4/6 inhibitor naive participants
Lasso di tempo: Up to approximately 36 months

ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator assessment per RECIST 1.1.
Up to approximately 36 months

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
[Part 1] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Lasso di tempo: Up to approximately 37 months

Safety is determined by incidence, type, and severity of adverse events per CTCAE v4.03 criteria including changes in laboratory values, vital signs, liver assessments, renal and cardiac assessments.
Up to approximately 37 months
[Part 1] Number of participants with dose adjustments
Lasso di tempo: Up to approximately 37 months

The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) and the reasons
Up to approximately 37 months
[Part 1] Dose intensity for alpelisib and fulvestrant
Lasso di tempo: Up to approximately 37 months

The dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity)
Up to approximately 37 months
[Part 1] Duration of exposure for alpelisib and fulvestrant
Lasso di tempo: Up to approximately 37 months

The duration of exposure (in months) to alpelisib and fulvestrant
Up to approximately 37 months
[Part 1] Plasma concentrations of alpelisib in combination with fulvestrant
Lasso di tempo: Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle = 28 days)

Summary statistics of alpelisib plasma concentrations by time point and dose level
Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle = 28 days)
[Part 2] Overall Response Rate (ORR) for CDK4/6 inhibitor pre-treated participants
Lasso di tempo: Up to approximately 36 months

ORR is defined as the proportion of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on local investigator assessment per RECIST 1.1.
Up to approximately 36 months
[Part 2] Progression Free Survival (PFS)
Lasso di tempo: Up to approximately 36 months

PFS is defined as the time from the date of first administration of study treatment until the date of the first documented progression or death due to any cause. PFS will be assessed based on local investigator assessment per RECIST 1.1.
Up to approximately 36 months
[Part 2] Overall Survival (OS)
Lasso di tempo: Up to approximately 60 months

OS is defined as the time from date of first administration of study treatment until date of death due to any cause.
Up to approximately 60 months
[Part 2] Clinical Benefit Rate (CBR)
Lasso di tempo: Up to approximately 36 months

CBR is defined as the proportion of participants with a best overall response of confirmed CR, or confirmed PR, or an overall response of confirmed stable disease (SD), lasting for a duration of at least 24 weeks. CR, PR, and SD are defined based on local investigator assessment per RECIST 1.1.
Up to approximately 36 months
[Part 2] Duration of Response (DOR)
Lasso di tempo: Up to approximately 36 months

DOR only applies to participants whose best overall response is CR or PR based on local investigator assessment per RECIST 1.1. The start date is the date of first documented response of CR or PR (i.e. the start date of response, not the date when response was confirmed), and the end date is defined as the date of the first documented progression or death due to underlying cancer.
Up to approximately 36 months
[Part 2] Time to Response (TTR)
Lasso di tempo: Up to approximately 36 months

TTR is defined as the time from the date of first administration of study treatment until the date of the first documented response of either CR or PR, which must be subsequently confirmed (although date of initial response is used, not date of confirmation).
Up to approximately 36 months
[Part 2] Time to definitive deterioration of Eastern Cooperative Oncology Group (ECOG) performance status
Lasso di tempo: Up to approximately 36 months

Time to definitive deterioration in ECOG performance status is defined as the time from the date of first administration to the date when ECOG performance status has definitively deteriorated by at least one category compared with baseline. Deterioration is considered definitive if there is no subsequent improvement in ECOG performance status back to the baseline category or above.
Up to approximately 36 months
[Part 2] Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
Lasso di tempo: Up to approximately 37 months

Incidence, type, and severity of adverse events per CTCAE v4.03 criteria including changes in laboratory values, vital signs, liver assessments, renal and cardiac assessments
Up to approximately 37 months
[Part 2] Number of participants with dose adjustments
Lasso di tempo: Up to approximately 37 months

The number and percentage of participants with dose interruptions and dose reductions
Up to approximately 37 months
[Part 2] Dose intensity for alpelisib and fulvestrant
Lasso di tempo: Up to approximately 37 months

The dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity)
Up to approximately 37 months
[Part 2] Duration of exposure for alpelisib and fulvestrant
Lasso di tempo: Up to approximately 37 months

The duration of exposure (in months) to alpelisib and fulvestrant
Up to approximately 37 months
[Part 2] Plasma concentrations of alpelisib in combination with fulvestrant
Lasso di tempo: Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle= 28 days)

Summary statistics of alpelisib plasma concentrations by time point and dose level
Cycle 1 Day 8 (pre-dose), 15 (pre-dose, post-dose 1 hour, 3 hours) and Day 1 of Cycles 2, 4, 6, 8 (pre-dose) (Cycle= 28 days)

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Novartis Pharmaceuticals

Investigatori

  • Direttore dello studio: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

8 gennaio 2021

Completamento primario (Stimato)

26 febbraio 2027

Completamento dello studio (Stimato)

27 febbraio 2027

Date di iscrizione allo studio

Primo inviato

19 agosto 2020

Primo inviato che soddisfa i criteri di controllo qualità

19 agosto 2020

Primo Inserito (Effettivo)

24 agosto 2020

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

18 settembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

17 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • CBYL719C1201

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

SÌ

Descrizione del piano IPD

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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