This study is in progress, not accepting new patients

Study Assessing the Efficacy and Safety of Alpelisib + Nab-paclitaxel in Subjects With Advanced TNBC Who Carry Either a PIK3CA Mutation or Have PTEN Loss

a study on Breast Cancer Triple-Negative Breast Cancer PIK3CA Mutation

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
completion around

Description

Summary

The purpose of this study was to determine whether treatment with alpelisib in combination with nab-paclitaxel is safe and effective in subjects with advanced triple negative breast cancer (aTNBC) who carry either a PIK3CA mutation (Study Part A) or have PTEN loss (Study Part B1) or PTEN loss without PIK3CA mutation (Study Part B2)

Official Title

A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Alpelisib (BYL719) in Combination With Nab-paclitaxel in Patients With Advanced Triple Negative Breast Cancer With Either Phosphoinositide-3-kinase Catalytic Subunit Alpha (PIK3CA) Mutation or Phosphatase and Tensin Homolog Protein (PTEN) Loss Without PIK3CA Mutation

Details

The recruitment of Part A was halted on 11-Nov-2022 due to slow recruitment. Since Part B1 did not meet its primary objective for confirmed overall response rate, the Part B2 was not initiated, and the recruitment was halted for the entire study.

Upon confirming either PIK3CA mutation and/or PTEN loss status, advanced TNBC participants meeting all other eligibility criteria were assigned to either Part A (PIK3CA mutation regardless of PTEN loss) or Part B1 (PTEN loss with PIK3CA unknown or non-mutant).

In Part A, participants were randomized a 1:1 to receive either:

  • alpelisib 300 mg daily orally + nab-paclitaxel 100 mg/m2 intravenously (IV) on Days 1, 8, and 15 of each 28-day cycle or
  • placebo + nab-paclitaxel 100 mg/m2 IV on Days 1, 8, and 15 of each 28-day cycle.

In Part B1, participants received alpelisib 300 mg daily orally + nab-paclitaxel 100 mg/m2 IV on Days 1, 8, and 15 of each 28-day cycle.

Keywords

Triple Negative Breast Neoplasms, Triple Negative Breast Cancer, alpelisib, BYL719, nab-paclitaxel, PIK3CA mutation, PTEN loss, Breast Neoplasms, Paclitaxel, alpelisib + nab-paclitaxel

Eligibility

You can join if…

Open to people ages 18 years and up

  • Participant has histologically confirmed diagnosis of advanced (loco-regionally recurrent and not amenable to curative therapy), or metastatic (stage IV) TNBC
  • Participant has either a measurable disease per RECIST 1.1 criteria or, if no measurable disease is present, then at least one predominantly lytic bone lesion or mixed lytic-blastic bone lesion with identifiable soft tissue component (that can be evaluated by CT/MRI) must be present. Part B1: Participants must have measurable disease
  • Participant has adequate tumor tissue to identify the PIK3CA mutation status (either carrying a mutation or without a mutation) and the PTEN loss status; both of which will determine whether the subject can be allocated to Part A - PIK3CA mutation regardless of PTEN status; or to Part B1 - PTEN loss or to Part B2 - PTEN loss without a PIK3CA mutation
  • Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Participant has received no more than one line of therapy for metastatic disease
  • Participant has adequate bone marrow and organ function

You CAN'T join if...

  • Participant has received prior treatment with any PI3K, mTOR or AKT inhibitor
  • Participant has a known hypersensitivity to alpelisib, nab-paclitaxel or to any of their excipients
  • Participant has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1; with the exception of alopecia
  • Participant has central nervous system (CNS) involvement which was not previously treated and/or was newly detected at screening
  • Participant with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on Fasting Plasma Glucose and HbA1c
  • Participant has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection) based on investigator discretion
  • Participant has a history of acute pancreatitis within 1 year prior to screening or past medical history of chronic pancreatitis
  • Participant has currently documented pneumonitis/interstitial lung disease
  • Participant has a history of severe cutaneous reactions, such as Steven-Johnson Syndrome (SJS), erythema multiforme (EM),Toxic Epidermal Necrolysis (TEN) or Drug Reaction with Eosinophilia and Systemic Syndrome (DRESS)
  • Participant with unresolved osteonecrosis of the jaw

Locations

  • University Of California LA Santa Monica Location
    Los Angeles California 90095 United States
  • Novartis Investigative Site
    Monterrey Nuevo Leon 64460 Mexico

Details

Status
in progress, not accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Novartis Pharmaceuticals
ID
NCT04251533
Phase
Phase 3 research study
Study Type
Interventional
Participants
About 137 people participating
Last Updated