Clinical trial NCT02088684: Study of LEE011 With Fulvestrant and BYL719 or BKM120 in Advanced Breast Cancer
Official title: A Phase Ib/II Study of LEE011 in Combination With Fulvestrant and BYL719 or BKM120 in the Treatment of Postmenopausal Women With Hormone Receptor Positive, HER2 Negative Locally Recurrent or Advanced Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Breast Cancer
Keywords: Hormone receptor positive, HER2 negative
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-03-17
Enrollment: 70
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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)

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 inclusion/exclusion criteria may apply

Primary outcomes:
measure: Incidence of Dose limiting toxicities (DLTs) - Phase lb only
timeFrame: 28 days
measure: Progression free survival (PFS) - Phase ll only
timeFrame: 36 months
Secondary outcomes:
measure: Safety and Tolerability of the combinations of LEE011 with fulvestrant, LEE011 + BKM120 with fulvestrant and LEE011 + BYL719 with fulvestrant
timeFrame: 36 months
measure: Plasma concentration-time profiles of LEE011, BKM120, BYL719 and fulvestrant.
timeFrame: 36 months
measure: Overall Response Rate (ORR)
timeFrame: 36 months
measure: Duration of Response (DOR)
timeFrame: 36 months
measure: Progression Free Survival (PFS) (phase l only)
timeFrame: 36 months
measure: Overall Survival (OS) - Phase II only
timeFrame: 36 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham/ Kirklin Clinic Dept Onc
state: Alabama
city: Boston
country: United States
facility: Dana Farber Cancer Institute Onc. Dept.
state: Massachusetts
city: Nashville
country: United States
facility: Sarah Cannon Research Institute Onc Dept
state: Tennessee
city: Lyon Cedex
country: France
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan ROC
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Tolaney SM, Im YH, Calvo E, Lu YS, Hamilton E, Forero-Torres A, Bachelot T, Maur M, Fasolo A, Tiedt R, Nardi L, Stammberger U, Abdelhady AM, Ruan S, Lee SC. Phase Ib Study of Ribociclib plus Fulvestrant and Ribociclib plus Fulvestrant plus PI3K Inhibitor (Alpelisib or Buparlisib) for HR+ Advanced Breast Cancer. Clin Cancer Res. 2021 Jan 15;27(2):418-428. doi: 10.1158/1078-0432.CCR-20-0645. Epub 2020 Sep 4.