Hormone receptor positive, HER2-negative advanced breast cancer MedDRA version: 21.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Participant is an adult = 18 years old at the time of informed consentand has signed informed consent before any trial related activities and according to local guidelines. • 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 (Fluorescent in situ hybridization (FISH), Chromogenic in situ hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is required by local laboratory testing. • Participant has at least one measurable lesion as per RECIST v1.1 criteria as assessed by Investigator (a lesion at a previously irradiated site may only be counted as a target lesion if there is clear sign of progression since the irradiation). • Participant has recurrence or progression of disease during or after combined AI (i.e. letrozole, anastrozole, exemestane) and CDK4/6 inhibitor therapy. The combined AI and CDK4/6 inhibitor therapy does not need to be the latest treatment regimen (including adjuvant setting). • Participant has received = 2 prior lines of systemic therapies overall in the metastatic setting, of which a maximum of 1 line of prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy) is permitted . • The presence of PIK3CA mutation(s) determined in tumor tissue prior to enrollment either by a Novartis designated laboratory or in tumor tissue or plasma ctDNA by a local laboratory using a Food and Drug Administration (FDA)-approved PIK3CA Companion Diagnostics (CDx) test for alpelisib or the CE-IVD QIAGEN Therascreen® PIK3CA RGQ PCR test. • If female, then the participant must be in postmenopausal status Further inclusion criteria and details are described in the protocol 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 127 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 107
Exclusion criteria
Exclusion criteria: - Participant with symptomatic visceral disease or any disease burden that makes the participant ineligible for endocrine therapy (ET) per the investigator’s best judgment. - Participant who relapsed with documented evidence of progression more than 12 months from completion of (neo)adjuvant endocrine/endocrine-based therapy with no treatment for metastatic disease - Participant has received prior treatment with fulvestrant, any oral selective estrogen receptor degrader (SERD), any Phosphatidylinositol- 3-Kinase (PI3K), mammalian Target of Rapamycin (mTOR) or Protein Kinase B (AKT) inhibitor Further exclusion criteria and details are described in the protocol
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Overall survival - Overall response rate (ORR) with confirmed response, clinical benefit rate (CBR) with confirmed response, duration of response (DOR) with confirmed response, and time to response (TTR) based on BIRC assessment and RECIST v1.1 - PFS based on BIRC assessment and using RECIST v1.1 criteria for participants by PIK3CA mutation status assessed in ctDNA at baseline - Incidence, type and severity of adverse events per CTCAE v4.03 criteria - Time to definitive deterioration of ECOG performance status from baseline - Time to definitive (10%) deterioration in the global health status/Quality of Life (QoL) and symptom scale scores of the EORTC QLQ-C30 Change from baseline in global health status/QoL and symptom scale scores of the EORTC QLQ-C30 - Time from randomization to objective tumour progression on next line treatment or death from any cause (PFS2);Timepoint(s) of evaluation of this end point: - From the date of randomization to the date of death for the OS - From the date of randomization up to maximum duration of 60 months for the other secondary endpoints | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival (PFS) compared to treatment with placebo plus fulvestrant;Secondary Objective: To determine whether treatment with alpelisib plus fulvestrant prolongs overall survival (OS) compared to treatment with placebo plus fulvestrant To evaluate alpelisib plus fulvestrant compared to placebo plus fulvestrant, with regards to objective response by RECIST 1.1 criteria To evaluate the association between PIK3CA mutation status as measured in circulating tumor deoxyribonucleic acid (ctDNA) at baseline with PFS upon treatment with alpelisib To assess safety and tolerability of alpelisib in combination with fulvestrant compared to placebo in combination with fulvestrant To evaluate treatment with alpelisib plus fulvestrant compared to placebo plus fulvestrant, with respect to time to deterioration of Eastern Cooperative Oncology Group (ECOG) performance status To evaluate patient-reported outcomes of alpelisib plus fulvestrant compared to placebo and fulvestrant To explore the long-term benefit intermediate to PFS and OS;Primary end point(s): - Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria;Timepoint(s) of evaluation of this end point: The primary efficacy and safety analyses will be performed after observing approximately 165 PFS events per BIRC assessment | — |
Countries
Belgium, Bulgaria, Canada, Czechia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, United Kingdom
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed