Breast Cancer Hormone receptor positive, HER2 negative MedDRA version: 16.1 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: ND
Product Code: LEE011
Pharmaceutical Form: Capsule
INN or Proposed INN: ND
CAS Number: ND
Current Sponsor code: LEE011
Other descriptive name: LEE011
Concentration unit: mg milligram(s
Sponsors
Novartis Farma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Postmenopausal, Hormone receptor positive (HR+), HER2 negative breast cancer; - Phase Ib - Unlimited number of lines of endocrine therapy and up to two lines of cytotoxic chemotherapy in the metastatic setting. - Phase II - Unlimited number of lines of endocrine therapy and one line of cytotoxic chemotherapy in the metastatic setting Other protocol-defined inclusioncriteria may apply 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 47 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 173
Exclusion criteria
Exclusion criteria: - HER2-overexpression in the patient's tumor tissue; - inadequate bone marrow function or evidence of end-organ damage; - severe or uncontrolled medical issues; - diabetes mellitus. Other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The purpose of this trial is to explore the clinical utility of the three investigational agents in HR+, HER2-breast cancer. LEE011 (CDK4/6 inhibitor), BKM120 (PI3K-pan class I-inhibitor) and BYL719 (PI3K-alpha specific class I inhibitor) in combination with fulvestrant. This is a multi-center, open-label Phase Ib/II study. The Phase Ib portion of the study is a dose escalation to estimate the MTD and/or RP2D for three regimens: LEE011 with fulvestrant; LEE011 and BKM120 with fulvestrant; LEE011and BYL719 with fulvestrant. The Phase II portion of the study will be a randomized study to assess the anti-tumor activity as well as safety and tolerability of LEE011 with fulvestrant to LEE011 and BKM120 with fulvestrant, and LEE011 and BYL719 with fulvestrant in patients with ER+/HER2- locally advanced or metastatic breast cancer. ;Secondary Objective: 1-Safety and Tolerability of the combinations of LEE011 with fulvestrant, LEE011 + BKM120 with fulvestrant and LEE011 + BYL719 with fulvestrant 2- To characterize plasma concentration-time profiles of LEE011, BKM120, BYL719 and fulvestrant. 3-To assess preliminary clinical anti-tumor activity ;Primary end point(s): 1-phase Ib: Dose limiting toxicities 2- phase II: Progression Free Survival per RECIST v 1.1 by local investigator assessment;Timepoint(s) of evaluation of this end point: 1-28 days 2- 36 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1-Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity 2- PK parameters for LEE011, BKM120 and BYL719, including but not limited to Cmax, Cmin, Tmax, AUCtau, accumulation ratio (Racc),and Ctrough values for fulvestrant. 3- Overall Response Rate (ORR) 4- Duration of Response (DOR) 5- Progression Free Survival (PFS) (pahse l only) 6-Overall Survival (OS) - Phase II only;Timepoint(s) of evaluation of this end point: 36 months for all listed Secondary End points | — |
Countries
Austria, Brazil, Canada, Czech Republic, France, Hungary, Israel, Italy, Korea, Republic of, Poland, Singapore, Spain, Switzerland, Taiwan, Thailand, United Kingdom, United States
Contacts
Public ContactDrug Regulatory Affairs
NOVARTIS FARMA S.p.A
Outcome results
None listed