Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer
Conditions
Keywords
Advanced breast cancer, Hormone receptor positive, HER2-negative, LEE011,, Letrozole, Tamoxifen, Fulvestrant, Postmenopausal Asian women, Pre and Postmenopausal Japanese women
Brief summary
The purpose of the Phase Ib is to: 1. determine the recommended dose of LEE011 in combination with a standard dose of letrozole as well as to provide additional safety and anti-tumor activity data in Asian non-Japanese patients 2. determine the recommended dose of LEE011 in combination with a standard dose of letrozole as well as to provide additional safety and activity data in Japanese patients 3. evaluate the safety and anti-tumor activity of LEE011 at the RP2D established in the dose escalation part in combination with a standard dose of letrozole, fulvestrant or tamoxifen plus goserelin in Japanese patients.
Interventions
DRUGLEE011
LEE011 as 50 mg and 200 mg hard gelatin oral capsules as individual patient supply packaged in bottles. LEE011 will be taken QD - days 1-21 of each 28 days cycle.
DRUGLetrozole
25mg
DRUGTamoxifen
20 mg
DRUGFulvestrant
500 mg
DRUGgoserelin
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy (surgery and/or radiotherapy). * Patient has a histologically and/or cytologically confirmed diagnosis of estrogen receptor positive and/or progesterone receptor positive breast cancer * Patient has HER2-negative breast cancer * Patient has adequate bone marrow and organ function
Exclusion criteria
* Patient who received any CDK4/6 inhibitor. * Patient has a known hypersensitivity to any of the excipients of LEE011 or letrozole * Patients with inflammatory breast cancer. * Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer * Patient is currently using other anti-cancer therapy * Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects. * Patient who has received radiotherapy ≤ 4 weeks * Patient has a concurrent malignancy or malignancy within 3 years * Patient has metastases to the central nervous system (CNS). * Patient has a known history of HIV infection Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase Ib Dose escalation - Frequency of dose limiting toxicities (DLTs) | first cycle (28 days) | DLTs at each dose level associated with administration of LEE011 and letrozole |
| Phase Ib Dose Expansion: Number of participants with adverse events (AEs) | 18 months | This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of AEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant |
| Phase Ib Dose Expansion: Number of participants with serious adverse events (SAEs) | 18 months | This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of SAEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate (CBR) - Phase Ib dose expansion | 18 months | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant |
| Composite Plasma pharmacokinetics (PK) parameters of LEE011 (and relevant metabolites) and letrozole - Phase Ib | C1D1, C1D2, C1D8, C1D15, C1D21, C1D22, C2D15, C3D15 | As assessed by PK parameters such as Cmax, Tmax, AUC0-24hours, accumulation ratio and Ctrough for LEE011 (and relevant metabolites) and letrozole, tamoxifen and fulvestrant |
| Progression Free Survival (PFS) as per RECIST v1.1- phase Ib dose expansion | 18 months | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant |
| Number of participants with adverse events (AEs) - Phase Ib dose escalation | 18 months | This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of AEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant |
| Disease Control Rate (DCR) - Phase Ib dose expansion | 18 months | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant |
| Duration of Response (DOR) - Phase Ib dose expansion | 18 months | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant |
| Overall Survival (OS) - Phase Ib dose expansion | 18 months | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant |
| Number of participants with serious adverse events (SAEs) - Phase Ib dose escalation | 18 months | This will be defined by changes in hematology and chemistry values, vital signs and ECGs, frequency and duration of SAEs, lab abnormalities and other safety parameters. For LEE011 and letrozole or tamoxifen or fulvestrant |
| Overall Response Rate (ORR) - Phase Ib dose expansion | 18 months | Anti-tumor activity for LEE011 and letrozole or tamoxifen or fulvestrant |
Countries
Hong Kong, Japan, Singapore
Outcome results
None listed