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

Advanced or Metastatic Breast Cancer Clinical Trial

— LeeBLet  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02154776
• Other study ID #: CLEE011A2112C
• Status: Completed
• Phase: Phase 1
• Start date: June 27, 2014
• Est. completion date: October 26, 2016

Study information

• Verified date: July 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: October 26, 2016
• Est. primary completion date: October 26, 2016
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced or Metastatic Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• LEE011
3 weeks on and 1 week off
• Buparlisib
daily
• Letrozole
2.5 mg daily;

Locations

Country	Name	City	State
Spain	Novartis Investigative Site	Madrid
United States	Medical University of South Carolina SC	Charleston	South Carolina
United States	Horizon Oncology Center SC	Lafayette	Indiana
United States	University of California at Los Angeles UCLA SC	Los Angeles	California
United States	University of Utah / Huntsman Cancer Institute SC-3	Salt Lake City	Utah
United States	South Texas Accelerated Research Therapeutics SC	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities (DLTs)	Dose Escalation Phase: Frequency of DLTs at each dose level associated with administration of LEE011, buparlisib, and letrozole in a 28 day cycle	28 days
Primary	Safety and tolerability of the combination of LEE011, buparlisib, and letrozole	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.	approximately 25 months
Secondary	Safety and tolerabiity of the combination of LEE011, buparlisib, and letrozole	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.	approximately 25 months
Secondary	Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles	Dose Escalation Phase: When given in combination as well any other clinically significant metabolites that may be identified	approximately 25 months
Secondary	Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles	Dose Expansion Phase: When given in combination as well as any other clinically significant metabolites that may be identified	approximately 25 months
Secondary	Disease control rate	Dose Expansion Phase: Proportion of patients with the best overall response of CR (complete response), PR (partial response), or SD (stable disease)	approximately 25 months
Secondary	PFS (progression free survival)	Dose Expansion Phase: Time from date of start of treatment to date of first documented progression or death due to any cause.	approximately 25 months

External Links

•   Results for CLEE011A2112C can be found on the Novartis Clinical Trial Results Website