Hormone receptor positive, HER2-negative advanced breast cancer MedDRA version: 21.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Alpelisib
Product Code: BYL719
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ALPELISIB
CAS Number: 1217486-61-7
Current Sponsor code: BYL719
Concentration unit: mg milligr
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Patient is male or female 18 years or older - Patient is identified PIK3CA mutant status - Patient has confirmed HER2-negative advanced breast cancer (aBC) -Patient must be diagnosed with aBC with documented progression on or after prior treatment - Patient has histological and/or cytological confirmed ER+ and/or PgR+ aBC - Patient has either measurable disease per RECIST v1.1 or at least one predominantly lytic bone lesion must be present - ECOG function of greater or equal to 2 - Patient has adequate bone marrow function - Patient has adequate liver and renal function Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 280
Exclusion criteria
Exclusion criteria: - Patient has a known hypersensitivity to alpelisib, fulvestrant or letrozole or to any of the excipients of alpelisib, fulvestrant or letrozole - patient has received prior treatment with any PI3K inhibitors - patient with with an established diagnosis of diabetes mellitus type I or uncontrolled type II - patient with clinically manifest diabetes mellitus, or documented steroid induced diabetes mellitus -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 -Bilateral diffuse lymphangitis carcinomatosis -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 based on investigator discretion -Patient has documented pneumonitis which is active and requiring treatment -Patient has a history of severe cutaneous reactions like Stevens Johnson-Syndrome (SJS), Erythema Multiforme (EM), or Toxic Epidermal Necrolysis (TEN) or Drug Reaction with Eosinphilia and Systemic Symptoms (DRESS) -Subjects with unresolved osteonecrosis of the jaw
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the proportion of patients who are alive without disease progression at 6 months based on local investigator assessment per RECIST v1.1 in cohort A and C (alpelisib in combination with fulvestrant) and cohort B (alpelisib in combination with letrozole) among patients with HR+, HER2-negative aBC harboring a PIK3CA mutation who have progressed on or after prior treatments;Secondary Objective: To assess PFS based on local investigator assessment for each cohort To assess PFS on next-line treatment (PFS2) for each cohort To assess overall response rate (ORR) and clinical benefit rate (CBR) based on local investigator assessment for each cohort To assess duration of response (DOR) in patients with confirmed complete response (CR) or PR for each cohort. To assess Overall Survival for each cohort. To evaluate the safety and tolerability of the combination for each cohort;Primary end point(s): The percentage of patients who are alive without disease progression;Timepoint(s) of evaluation of this end point: Date of first dose to approximately 6 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Progression free survival (PFS) for each cohort Progression free survival (PFS) on next line treatment PFS2) for each cohort Percentage of participants Overall response rate (ORR) for each cohort Percentage of participants with clinical benefit rate (CBR) for each cohort Duration of response (DOR) Overall Survival Further secondary objectives and details are described in the protocol;Timepoint(s) of evaluation of this end point: date of first dose to up to approximately 25 months Date of first dose to date of first documented progression up to approximately 25 months Date of first dose and up to approximately 25 months Date of first dose and up to approximately 25 months Date of first documented response to first documented progression or death up to approximately 25 months | — |
Countries
Argentina, Belgium, Bulgaria, Canada, Chile, Denmark, France, Germany, India, Israel, Italy, Japan, Mexico, Netherlands, Singapore, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed