Overview

This trial is active, not recruiting.

Condition advanced or metastatic breast cancer
Treatments lee011, buparlisib, letrozole
Phase phase 1
Targets PI3K, CDK4, CDK6
Sponsor Novartis Pharmaceuticals
Start date June 2014
End date July 2017
Trial size 13 participants
Trial identifier NCT02154776, CLEE011A2112C

Summary

This is a multi-center, open-label, non-randomized, phase I study

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Arm
(Experimental)
open label, dose escalation evaluating max tolerated dose of the triple combination
lee011
3 weeks on and 1 week off
buparlisib
daily
letrozole
2.5 mg daily;

Primary Outcomes

Measure
Incidence of dose-limiting toxicities (DLTs)
time frame: 28 days
Safety and tolerability of the combination of LEE011, buparlisib, and letrozole
time frame: approximately 25 months

Secondary Outcomes

Measure
Safety and tolerabiity of the combination of LEE011, buparlisib, and letrozole
time frame: approximately 25 months
Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles
time frame: approximately 25 months
Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles
time frame: approximately 25 months
Disease control rate
time frame: approximately 25 months
PFS (progression free survival)
time frame: approximately 25 months

Eligibility Criteria

Female participants at least 18 years old.

Inclusion Criteria: 1. Women with advanced (recurrent or metastatic) breast cancer who received no prior therapy for advanced disease. 2. Patient is postmenopausal. 3. Patient may have received ≤ 2 lines of chemotherapy for metastatic or recurrent breast cancer in the dose-escalation phase. 4. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory. 5. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required by local laboratory testing. 6. Patient must have either: - Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria or at least one predominantly lytic bone lesion Exclusion Criteria: 1. Patient who received any CDK4/6 or PI3K inhibitor. 2. Patient has active cardiac disease or a history of cardiac dysfunction including any of the following: - History of angina pectoris, symptomatic pericarditis, or myocardial infarction within 12 months prior to study entry - History of documented congestive heart failure (New York Heart Association functional classification III-IV) - Documented cardiomyopathy - Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) - History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality in the previous 12 months. - On screening, any of the following cardiac parameters: bradycardia (heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval > 220 msec, QRS interval >109 msec, or QTcF >450 msec. Systolic blood pressure >160 or <90 mmHg 3. Patient is currently receiving any of the following medications: - That are known strong inducers or inhibitors of CYP3A4. - That have a known risk to prolong the QT interval or induce Torsades de Pointes. - That have a narrow therapeutic window and are predominantly metabolized through CYP3A4. 4. Certain scores on an anxiety and depression mood questionnaires

Additional Information

Official title A Phase 1 Dose Escalation Study of LEE011 in Combination With Buparlisib and Letrozole for the Treatment of HR+, HER2-negative Post-menopausal Women With Locally Advanced or Metastatic Breast Cancer.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by Novartis.