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BYLieve: A Phase II, Multicenter, Open-label, Three-cohort, Non- Comparative Study to Assess the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole in Patients With PIK3CA Mutant, Hormone Receptor (HR) Positive, HER2-negative Advanced Breast Cancer (aBC), Who Have Progressed on or After Prior Treatments - CBYL719X2402

Studio Clinico

Patologia: Neoplasie della mammella

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: No

Fase di studio: II

Linee di trattamento: Seconda linea, Terza/N linea

Criteri di inclusione: 

1) Patient is male or female 18 years or older
- Males or females with advanced (locoregionally recurrent or metatstatic) breast cancer not amenable to curative therapy
- In case of women, both premenopausal and postmenopausal patients are allowed to be included in study; menopausal status is relevant for the requirement of LHRH agonist (examples for use in this study include but not limited to goserelin, leuprolide or locally available treatment) to be used concomitantly with alpelisib and letrozole/fulvestrant
    - Patient is postmenopausal woman defined as either:
      - Prior bilateral oophorectomy or
      - Age ≥60 or
      - Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression) and FSH and/or estradiol in the postmenopausal range per local normal range.
      If patient is taking tamoxifen or toremifene and age <60, then FSH and plasma estradiol levels should be in post-menopausal range per local normal range.
      Note: For women using therapy-induced amenorrhea other than ovarian radiation, goserelin or leuprolide, etc., serial measurements of FSH and/or estradiol are needed to ensure menopausal status
2) Patient is premenopausal defined as either:
    - Patient had last menstrual period within the last 12 months or
    - If on tamoxifen or toremifene with in the past 14 days, plasma estradiol and FSH must be in the premenopausal range per local normal range, or
    - In case of therapy induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal range per local normal range
- Patient has histological and/or cytological confirmed ER+ and/or PgR+ aBC
- Patient has confirmed HER2-negative advanced breast cancer (aBC)
- Patient has a PIK3CA mutation confirmed by Novartis designated central lab or patient has a pathology report confirming PIK3CA mutant status by certified laboratory (using validated PI3KCA mutation assay) either from tissue or blood and must (mandatory) send tumor tissue to Novartis designated central lab for confirmation of mutational status
- Patient must have:
    - Documented evidence of tumor progression on or after CDK 4/ 6 inhibitor combination treatment; CDK 4/6 inhibitor must be the last treatment regimen prior to study entry,
    - AI treatment (either in adjuvant or metastatic setting) and received systemic chemotherapy or ET as last treatment regimen in cohort C
    - Maintenance therapies, where applicable, must be regarded as part of the main treatment.
    - No more than two (2) prior anti-cancer therapies for aBC
    - Received no more than one prior regimen of chemotherapy in the metastatic setting
- Patient has either measurable disease per RECIST v1.1 or at least one predominantly lytic bone lesion must be present
ECOG performance status ≤ 2
Patient has fasting plasma glucose (FPG) ≤140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) ≤ 6.4% (both criteria have to be met)
- Patient has adequate bone marrow, coagulation, liver and renal function

Criteri di esclusione: 

- Patient has known hypersensitivity to alpelisib, fulvestrant or letrozole
- Patient has received prior treatment with any PI3K inhibitors
- Patient with an established diagnosis of diabetes mellitus type I or uncontrolled type II
- Patient has a concurrent malignancy or malignancy within 3 years of study screening period, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer
- Patient has received radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to enrollment, and who has not recovered to grade 1 or better from related side effects of such therapy
- History of acute pancreatitis within 1 year of screening or past medical history of pancreatitis
- Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
    - At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
    - Clinically stable CNS tumor at the time of screening untreated or without evidence of progressions for at least 4 weeks after treatment as determined by clinical examination and brain imaging (MRI or CT) during screening period and stable low dose of steroids for 2 weeks prior to initiating study treatment
- Patient with severe liver impairment (Child Pugh score B/C)
- Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs
- Patient has documented pneumonitis which is active and requiring treatment
- Patient has a history of Stevens-Johnson-Syndrome (SJS) or Toxic Epidermal Necroloysis (TEN)
- Patient is concurrently using other anti-cancer therapy. All anti-cancer therapy must be discontinued prior to day one of study treatment.

Trattamento sperimentale: 

- Prior CDK 4/6 + aromatase
Patients who received any CDK 4/6 inhibitor plus aromatase inhibitor as treatment (immediately prior) will receive alpelisib 500 mg oral.+ fulvestrant 500 mg intramuscular (i.m)

- Prior CDK 4/6 + fulvestrant
Patients who received any CDK 4/6 inhibitor plus fulvestrant as treatment (immediately prior) will receive alpelisib 300 mg oral + letrozole 2.5 mg oral

- Prior systemic chemo or ET
Patients who received systemic chemotherapy or endrocrine therapy (ET) as immediate prior treatment will receive alpelisib 300 mg oral + fulvestrant 500 mg i.m.

Trattamento di controllo: 


Note generali: 

Arruolamento aperto solo per la coorte C

Centri partecipanti

Nord Italia

Ospedale Papa Giovanni XXIII Bergamo
Piazza OMS 1 - 24127 Bergamo - BG


Ospedale S.Orsola Malpighi, Università di Bologna
Via Pietro Albertoni 15 - 40138 Bologna - BO
SSD Oncologia Medica Addarii


IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI

Riferimento: Dr.ssa Giulia Valeria Bianchi
Telefono: 0223903066


Istituto Europeo di Oncologia
Via Ripamonti 435 - 20141 Milano - MI
Senologia Medica

Riferimento: Dr. Marco Colleoni
Telefono: 0257489970


Centro Italia

Fondazione Policlinico A. Gemelli
Largo Agostino Gemelli 8 - 00168 Roma - RM


Sud Italia e isole

Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA
Oncologia Medica Senologica

Riferimento: Prof. Michelino De Laurentiis
Telefono: 0815903559

Informazioni Generali


Numero di iscrizione a registro: NCT03056755

Data di inserimento: 02.02.2018

Data di aggiornamento: 28.02.2020





Principal Investigator ITALIA

Fondazione IRCCS Istituto dei Tumori di Milano

Riferimento: Dr.ssa Giulia Valeria Bianchi

Telefono: 0223903066


Localita: Milano


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