This is a first-in-man trial, in which BYL719 will be administered to adult patients with advanced solid tumors, whose tumors have an alteration of the PIK3CA gene and whose disease has progressed despite standard therapy or for whom no standard therapy exists. A combination of BYL719 with fulvestrant will also be investigated in post-menopausal patients with locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene. The single agent MTD dose expansion cohort and the fulvestrant combination MTD dose expansion cohort will also include ER+/HER2- breast cancer patients whose tumors have the wild type PIK3CA gene
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
221
BYL719 is an oral α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor.
In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene. Fulvestrant is an estrogen receptor antagonist, administered by monthly intramuscular injection
UCSF Medical Center
San Francisco, California, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Sarah Cannon Research Institute Dept.ofSarahCannonCancerCtr(4)
Nashville, Tennessee, United States
Vanderbilt Univeristy SC
Nashville, Tennessee, United States
MD Anderson Cancer Center/University of Texas MD Anderson
Houston, Texas, United States
Novartis Investigative Site
Essen, Germany
Novartis Investigative Site
Würzburg, Germany
Novartis Investigative Site
Amsterdam, Netherlands
Novartis Investigative Site
Barcelona, Catalonia, Spain
Novartis Investigative Site
L'Hospitalet de Llobregat, Catalonia, Spain
...and 1 more locations
Incidence rate of dose limiting toxicities (DLT).
MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant.
Time frame: 5 years
Overall safety and tolerability of BYL719 as single agent and in combination with fulvestrant
Safety and tolerability: type, intensity, severity and seriousness of adverse events (AE) according to NCI CTCAE v. 4.0.
Time frame: 10 years
PK parameters of BYL719 as single agent and in combination with fulvestrant - AUC-tlast and AUC0-inf.
PK parameters AUC-tlast and AUC0-inf
Time frame: 5 years
PK parameters of BYL719 as single agent and in combination with fulvestrant - Cmax.
PK parameter Cmax
Time frame: 5 years
Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Tmax.
PK parameter Tmax
Time frame: 5 years
Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - CL/F.
PK parameter CL/F
Time frame: 5 years
Pharmaconkinetics of BYL719 as single agent and in combination with fulvestrant - Vz/F.
PK parameter Vz/F
Time frame: 5 years
Pharmacokinetics of BYL719 as single agent and in combination with fulvestrant - Terminal half-life (t1/2)
PK parameter t1/2
Time frame: 5 years
Preliminary efficacy of BYL719 as single agent and in combination with fulvestrant by measuring ORR.
Objective tumor response rate (ORR), defined as the sum of complete response and partial response as best reported response by RECIST 1.0 criteria (Novartis v2.0 guideline)
Time frame: 5 years
Progression-free survival at maximum tolerated dose
PFS at MTD
Time frame: 5 years
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