Study of LEE011 With Fulvestrant and BYL719 or BKM120 in Advanced Breast Cancer
- Conditions
- Breast Cancer
- Interventions
- Registration Number
- NCT02088684
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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 was planned to 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.
Approximately 216 adult women with ER+/HER2- locally advanced or metastatic breast cancer were planned to be enrolled.
- Detailed Description
On 31-May-2016 Novartis's made the decision decision to not open the Phase II portion of the study, for business reasons. Sufficient data had already been collected and no additional data for the triplet combinations was needed. As a result, the Phase II portion of the trial was not opened.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 70
- Postmenopausal, Hormone receptor positive (HR+), HER2 negative breast cancer
- Unlimited number of lines of endocrine therapy and up to two lines of cytotoxic chemotherapy in the metastatic setting (Phase Ib)
- Unlimited number of lines of endocrine therapy and one line of cytotoxic chemotherapy in the metastatic setting (Phase II)
- 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 inclusion/exclusion criteria may apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description LEE011 + BYL719 + fulvestrant LEE011 LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BYL719 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle. LEE011 + BKM120 + fulvestrant LEE011 LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BKM120 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle. LEE011 + BKM120 + fulvestrant fulvestrant LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BKM120 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle. LEE011 + BKM120 + fulvestrant BKM120 LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BKM120 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle. LEE011 + fulvestrant LEE011 LEE011 - 28 day cycles (3 weeks on, 1 week off) or (continuous daily dosing - dose escalating) fulvestrant - 500 mg i.m. given on Day 1 and Day 15 of Cycle 1, then on Day 1 of each subsequent cycle. LEE011 + BYL719 + fulvestrant BYL719 LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BYL719 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle. LEE011 + BYL719 + fulvestrant fulvestrant LEE011 - 28 day cycles (21 days followed by a 7 day break - dose escalating) BYL719 - daily (dose escalating) fulvestrant - i.m. - 500 mg given on day 1 and day 15 of Cycle 1, then on Day 1 of each subsequent cycle. LEE011 + fulvestrant fulvestrant LEE011 - 28 day cycles (3 weeks on, 1 week off) or (continuous daily dosing - dose escalating) fulvestrant - 500 mg i.m. given on Day 1 and Day 15 of Cycle 1, then on Day 1 of each subsequent cycle.
- Primary Outcome Measures
Name Time Method Incidence of Dose limiting toxicities (DLTs) - Phase lb only 28 days Dose limiting toxicities
Progression free survival (PFS) - Phase ll only 36 months Progression Free Survival per RECIST v 1.1 by local investigator assessment
- Secondary Outcome Measures
Name Time Method Safety and Tolerability of the combinations of LEE011 with fulvestrant, LEE011 + BKM120 with fulvestrant and LEE011 + BYL719 with fulvestrant 36 months Adverse Events (AEs), serious AEs (SAEs), changes in hematology and chemistry values, vital signs, electrocardiograms (ECGs), dose interruptions, reductions and dose intensity
Overall Response Rate (ORR) 36 months ORR is defined as the proportion of patients with a best overall response of complete response or partial response.
Progression Free Survival (PFS) (phase l only) 36 months PFS is the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause.
Duration of Response (DOR) 36 months Duration of Response is calculated as the time from the date of first documented response (complete response (CR) or partial response (PR)) to the first documented date of progression or death due to underlying cancer.
Overall Survival (OS) - Phase II only 36 months OS is defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival will be censored at the date of last known date patient alive.
Plasma concentration-time profiles of LEE011, BKM120, BYL719 and fulvestrant. 36 months To characterize the PK profiles of LEE011, BKM120, BYL719, and fulvestrant when used in combination as well as to evaluate any other clinically significant metabolites that may be identified. PK parameters for LEE011, BKM120 and BYL719, including but not limited to Cmax, Cmin, Tmax, AUCtau, accumulation ratio (Racc),and Ctrough values for fulvestrant.
Trial Locations
- Locations (4)
Sarah Cannon Research Institute Onc Dept
🇺🇸Nashville, Tennessee, United States
University of Alabama at Birmingham/ Kirklin Clinic Dept Onc
🇺🇸Birmingham, Alabama, United States
Dana Farber Cancer Institute Onc. Dept.
🇺🇸Boston, Massachusetts, United States
Novartis Investigative Site
🇬🇧Leicester, United Kingdom