LeeBLet: Dose Escalation Study of LEE011 in Combination With Buparlisib and Letrozole in HR+, HER2-negative Post-menopausal Women With Advanced Breast Cancer.

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT02154776

Collaborator

(none)

Enrollment

Locations

Arm

Actual Duration (Months)

2.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced or Metastatic Breast Cancer	Drug: LEE011 Drug: Buparlisib Drug: Letrozole	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

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.

Actual Study Start Date :

Jun 27, 2014

Actual Primary Completion Date :

Oct 26, 2016

Actual Study Completion Date :

Oct 26, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LEE011 + buparlisib + letrozole open label, dose escalation evaluating max tolerated dose of the triple combination	Drug: LEE011 3 weeks on and 1 week off Drug: Buparlisib daily Drug: Letrozole 2.5 mg daily;

Arm

Intervention/Treatment

Experimental: LEE011 + buparlisib + letrozole

open label, dose escalation evaluating max tolerated dose of the triple combination

Drug: LEE011

3 weeks on and 1 week off

Drug: Buparlisib

daily

Drug: Letrozole

2.5 mg daily;

Outcome Measures

Primary Outcome Measures

Incidence of dose-limiting toxicities (DLTs) [28 days]
Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of LEE011, buparlisib, and letrozole in a 28 day cycle
Safety and tolerability of the combination of LEE011, buparlisib, and letrozole [approximately 25 months]
Dose Expansion Phase: Incidence of AEs, SAEs (overal and severity), laboratory abnormalities, ECG, vital, dose interteruptions, dose reductions, and dose intensity as a measure of safety and tolerability.

Secondary Outcome Measures

Safety and tolerabiity of the combination of LEE011, buparlisib, and letrozole [approximately 25 months]
Dose Escalation Phase: Incidence of AEs, SAEs (overall and severity), laboratory abnormalities, ECG, vital, dose interterruptions, dose reductions, and dose intensity as a measure of safety and tolerability.
Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles [approximately 25 months]
Dose Escalation Phase: When given in combination as well any other clinically significant metabolites that may be identified
Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles [approximately 25 months]
Dose Expansion Phase: When given in combination as well as any other clinically significant metabolites that may be identified
Disease control rate [approximately 25 months]
Dose Expansion Phase: Proportion of patients with the best overall response of CR (complete response), PR (partial response), or SD (stable disease)
PFS (progression free survival) [approximately 25 months]
Dose Expansion Phase: Time from date of start of treatment to date of first documented progression or death due to any cause.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Inclusion Criteria:

Women with advanced (recurrent or metastatic) breast cancer who received no prior therapy for advanced disease.
Patient is postmenopausal.
Patient may have received ≤ 2 lines of chemotherapy for metastatic or recurrent breast cancer in the dose-escalation phase.
Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
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.
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:

Patient who received any CDK4/6 or PI3K inhibitor.
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

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.

Certain scores on an anxiety and depression mood questionnaires

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at Los Angeles UCLA SC	Los Angeles	California	United States	90095
2	Horizon Oncology Center SC	Lafayette	Indiana	United States	47905
3	Medical University of South Carolina SC	Charleston	South Carolina	United States	29425
4	South Texas Accelerated Research Therapeutics SC	San Antonio	Texas	United States	78922
5	University of Utah / Huntsman Cancer Institute SC-3	Salt Lake City	Utah	United States	84103
6	Novartis Investigative Site	Madrid		Spain	28007