A Phase Ib Trial of BYL719 (an α-Specific PI3K Inhibitor) in Combination With Endocrine Therapy in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer
PRIMARY OBJECTIVE: To determine the safety and tolerability of BYL719 given in combination
with endocrine therapy in post-menopausal patients with hormone receptor-positive metastatic
breast cancer by determining:
I. Dose limiting toxicities (DLTs) during the first 4 weeks of treatment (cycle 1).
II. Maximum tolerated dose (MTD) of BYL719 (PI3K inhibitor BYL719) given in combination with
letrozole.
III. Highest tolerated dose - ability to tolerate BYL719 with letrozole for a total of 8
weeks without development of prolonged >= grade 2 toxicities despite optimal medical
treatment.
SECONDARY OBJECTIVES: To determine the anti-tumor effect of the combinations of endocrine
therapy with BYL719 in post-menopausal patients with hormone receptor-positive metastatic
breast cancer by assessing:
I. Progression free survival (PFS). II. Objective response rate (ORR). III. Clinical benefit
rate (complete response [CR]+partial response [PR]+stable disease [SD] >= 6 months).
EXPLORATORY OBJECTIVES:
I. Pharmacokinetics of BYL719 in combination with letrozole: Plasma concentration-time
profiles and derived basic pharmacokinetic (PK) parameters of BYL719 and letrozole,
including but not limited to area under the plasma concentration-time curve from time zero
to the last measurable concentration (AUC0-tlast), AUC curve to infinite time (AUC0-inf),
maximum observed concentration (Cmax), time to peak concentration (Tmax), clearance over
bioavailability (CL/F), apparent volume of distribution (Vz/F) and the terminal half-life
(t1/2) and other PK parameters if deemed appropriate.
II. Correlation of response with alterations of the PI3K pathway: Mutational analysis of
PIK3CA (exons 9 and 20), phosphatase and tensin homolog (PTEN), and AKT1 in formalin-fixed
paraffin blocks (FFPB) from previous surgeries or fresh-frozen biopsies (if available) on
all patients enrolled in the trial.
OUTLINE: This is an open-label phase Ib dose-escalation study of the PI3K inhibitor BYL719
in combination with letrozole in post-menopausal patients with ER+ metastatic breast cancer.
Patients receive BYL719 orally (PO) once daily (QD) and letrozole PO QD. Courses repeat
every 4 weeks in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
Interventional
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose of BYL719 in combination with letrozole
Highest dose of BYL719 tested in which a DLT is experienced by 0 out of 3 or 1 of 6 patients, based on the NCI Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0
4 weeks
Yes
Ingrid Mayer
Principal Investigator
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
VICC BRE 12101
NCT01791478
April 2013
March 2015
Name | Location |
---|---|
Vanderbilt-Ingram Cancer Center | Nashville, Tennessee 37232-6838 |
Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |