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 Without PIK3CA Mutation

Purpose

The purpose of this study is 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 without PIK3CA mutation (Study Parts B1 and B2)

Condition

  • Triple Negative Breast Neoplasms

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Subject has histologically confirmed diagnosis of advanced (loco-regionally recurrent and not amenable to curative therapy, or metastatic (stage IV)) TNBC - Subject 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: patients must have measurable disease - Subject 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 B - PTEN loss without a PIK3CA mutation - Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 - Subject has received no more than one line of therapy for metastatic disease. - Subject has adequate bone marrow and organ function

Exclusion Criteria

  • Subject has received prior treatment with any PI3K, mTOR or AKT inhibitor - Subject has a known hypersensitivity to alpelisib, nab-paclitaxel or to any of their excipients - Subject has not recovered from all toxicities related to prior anticancer therapies to NCI CTCAE version 4.03 Grade ≤1; with the exception of alopecia - Subject has central nervous system (CNS) involvement - Subject with an established diagnosis of diabetes mellitus type I or uncontrolled type II based on Fasting Plasma Glucose and HbA1c - Subject 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 - Subject has a history of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis - Subject has currently documented pneumonitis/interstitial lung disease - Subject 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) - Subject with unresolved osteonecrosis of the jaw Other protocol-defined inclusion/exclusion criteria apply.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Factorial Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
alpelisib + nab-paclitaxel
Double-blinded, Randomized in a 1:1 ratio in Study Parts A and B2 Single arm Open label in Study Part B1
  • Drug: alpelisib
    300 mg orally once per day (QD)
    Other names:
    • BYL719
  • Drug: nab-paclitaxel
    100 mg/m² as IV infusion on Days 1, 8 and 15 of a 28-day cycle
    Other names:
    • abraxane
Placebo Comparator
placebo + nab-paclitaxel
Double-blinded, Randomized in a 1:1 ratio in Study Parts A and B2 Not applicable in Study Part B1
  • Drug: placebo
    300 mg orally once per day (QD)
    Other names:
    • alpelisib matching placebo
  • Drug: nab-paclitaxel
    100 mg/m² as IV infusion on Days 1, 8 and 15 of a 28-day cycle
    Other names:
    • abraxane

Recruiting Locations

University of Kansas Hospital and Medical Center DeptofUofKansas CancerCenter-2
Kansas City, Kansas 66160
Contact:
Jecinta Scott
913-588-2566
jscott11@kumc.edu

More Details

Status
Recruiting
Sponsor
Novartis Pharmaceuticals

Study Contact

Novartis Pharmaceuticals
1-888-669-6682
novartis.email@novartis.com