HER2-positive advanced breast cancer MedDRA version: 21.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Piqray
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ALPELISIB
CAS Number: 1217486-61-7
Current Sponsor code: BYL719
Other descriptive name: BYL719
Concentration unit: mg mi
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subject has histologically-confirmed HER2-positive breast cancer that is advanced (loco-regionally not amenable to surgery t or metastatic). - Subject has received pre-study induction therapy with up to and including a maximum of 8 cycles of a taxane (docetaxel, paclitaxel, or nab-paclitaxel), plus trastuzumab and pertuzumab. 4 or 5 cycles of taxane is permitted if discontinuation was due to toxicity - Subject has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 - Subject has adequate bone marrow and organ function - Applies only to Part 2: Subject has a PIK3CA mutation(s) present in tumor tissue prior to enrollment, as determined by a Novartis designated central laboratory. 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 368 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 158
Exclusion criteria
Exclusion criteria: - Subject with inflammatory breast cancer at screening. - Subject with evidence of disease progression during or following the pre-study induction therapy and prior to first dose of alpelisib (or alpelisib/alpelisib matching-placebo for Part 2) - Subject with an established diagnosis of diabetes mellitus type I or not controlled type II based on FPG and HbA1c - Subject has a known history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis - Subject has clinically significant, uncontrolled heart disease and/or recent cardiac events - Subject has a history of Steven-Johnson Syndrome (SJS), erythema multiforme (EM) or Toxic Epidermal Necrolysis (TEN). - Subject has currently documented pneumonitis/interstitial lung disease For Part 2 only: subject has known rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption, due to the excipient in the placebo tablet
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety run-in Part 1: To confirm the recommended phase 3 dose of alpelisib in combination with trastuzumab and pertuzumab Double-blind, randomized, placebo-controlled Part 2: To determine whether treatment with alpelisib in combination with trastuzumab and pertuzumab prolongs PFS compared to placebo in combination with trastuzumab and pertuzumab in adult patients with HER2-positive advanced breast cancer with a PIK3CA mutation ;Secondary Objective: Safety run-in Part 1: - To determine the safety and tolerability of alpelisib in combination with trastuzumab and pertuzumab - To characterize exposure of alpelisib when administered in combination with trastuzumab and pertuzumab Double-blind, randomized, placebo-controlled Part 2: - To determine whether treatment with alpelisib in combination with trastuzumab and pertuzumab prolongs OS in adult patients with HER2-positive advanced breast cancer with a PIK3CA mutation - To assess safety and efficacy - To characterize exposure of alpelisib, when administered in combination with trastuzumab and pertuzumab - To evaluate PROs of alpelisib in combination with trastuzumab and pertuzumab - To evaluate the association between PIK3CA mutation status as measured in ctDNA at baseline with PFS upon treatment with alpelisib - To evaluate alpelisib in combination with trastuzumab and pertuzumab with respect to time to deterioration of ECOG performance status;Primary end point(s): Part 1: Incidence of DLTs during the first 6 weeks of treatment for each dose level associated with administration of alpelisib in combination with trastuzumab and pertuzumab Part 2: PFS based on Investigator assessment using RECIST 1.1 criteria;Timepoint(s) of evaluation of this end point: Part 1: 6 weeks Part 2: up to approximately 38 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: To determine the safety and tolerability of alpelisib in combination with trastuzumab and pertuzumab Part 2: To determine whether treatment with alpelisib in combination with trastuzumab and pertuzumab prolongs OS compared to placebo in combination with trastuzumab and pertuzumab in adult patients with HER2-positive advanced breast cancer with a PIK3CA mutation;Timepoint(s) of evaluation of this end point: Part 1: up to approximately 38 months Part 2: up to approximately 70 months | — |
Countries
Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czechia, Finland, France, Germany, Greece, Hungary, Israel, Italy, Lebanon, Malaysia, Netherlands, Poland, Romania, Russian Federation, Singapore, Slovakia, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed