A Phase Ib Dose Escalation Study of the Combination of LEE011 With Letrozole and Dose Expansion of LEE011 With Hormonal Therapy for the Treatment of Pre-(With Goserelin) and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Novartis Pharmaceuticals
- Enrollment
- 88
- Locations
- 1
- Primary Endpoint
- Phase Ib Dose Expansion: Number of participants with serious adverse events (SAEs)
Study Overview
Brief Summary
The purpose of the Phase Ib is to:
- 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
- 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
- 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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts 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/exclusion criteria may apply
Arms & Interventions
LEE011 +Letrozole
LEE011 - 3 weeks on 1 week off Letrozole 2.5mg - Once daily
Intervention: LEE011 (Drug)
LEE011 +Letrozole
LEE011 - 3 weeks on 1 week off Letrozole 2.5mg - Once daily
Intervention: Letrozole (Drug)
LEE011 + Tamoxifen
LEE011 - 3 weeks on 1 week off Tamoxifen 20mg - Once daily
Intervention: Tamoxifen (Drug)
LEE011 + Tamoxifen
LEE011 - 3 weeks on 1 week off Tamoxifen 20mg - Once daily
Intervention: goserelin (Drug)
LEE011 + Fulvestrant
LEE011 - 3 weeks on 1 week off Fulvestrant 500 mg - Dosed every 28 days (Day 1 for each cycle) with 1 additional dose on Day 15 of Cycle 1
Intervention: Fulvestrant (Drug)
Outcomes
Primary Outcomes
Phase Ib Dose Expansion: Number of participants with serious adverse events (SAEs)
Time Frame: 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
Phase Ib Dose escalation - Frequency of dose limiting toxicities (DLTs)
Time Frame: 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)
Time Frame: 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
Secondary Outcomes
- Number of participants with adverse events (AEs) - Phase Ib dose escalation(18 months)
- Number of participants with serious adverse events (SAEs) - Phase Ib dose escalation(18 months)
- Overall Response Rate (ORR) - Phase Ib dose expansion(18 months)
- Clinical Benefit Rate (CBR) - Phase Ib dose expansion(18 months)
- Composite Plasma pharmacokinetics (PK) parameters of LEE011 (and relevant metabolites) and letrozole - Phase Ib(C1D1, C1D2, C1D8, C1D15, C1D21, C1D22, C2D15, C3D15)
- Progression Free Survival (PFS) as per RECIST v1.1- phase Ib dose expansion(18 months)
- Overall Survival (OS) - Phase Ib dose expansion(18 months)
- Disease Control Rate (DCR) - Phase Ib dose expansion(18 months)
- Duration of Response (DOR) - Phase Ib dose expansion(18 months)