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

NCT02154776 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CLEE011A2112C
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 6

Brief Summary

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

Conditions

Advanced or Metastatic Breast Cancer

Keywords

LEE011,; buparlisib,; letrozole,; HR +,; HER2 - negative,; post-menopausal,; breast cancer,; CDK 4/6,; PI3K,; MTD

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (5)

• Safety and tolerabiity of the combination of LEE011, buparlisib, and letrozole

  approximately 25 months

• Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles

  approximately 25 months

• Pharmacokinetic paramters such as AUClast and Cmax of LEE011, buparlisib, and letrozole in order to characterize the PK profiles

  approximately 25 months

• Disease control rate

  approximately 25 months

• PFS (progression free survival)

  approximately 25 months

Study Arms (1)

LEE011 + buparlisib + letrozole

EXPERIMENTAL

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

Drug: LEE011; Drug: Buparlisib; Drug: Letrozole

Interventions

LEE011 DRUG

3 weeks on and 1 week off

LEE011 + buparlisib + letrozole

Buparlisib DRUG

daily

LEE011 + buparlisib + letrozole

Letrozole DRUG

2.5 mg daily;

LEE011 + buparlisib + letrozole

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

University of California at Los Angeles UCLA SC

Los Angeles, California, 90095, United States

Location

Horizon Oncology Center SC

Lafayette, Indiana, 47905, United States

Location

Medical University of South Carolina SC

Charleston, South Carolina, 29425, United States

Location

South Texas Accelerated Research Therapeutics SC

San Antonio, Texas, 78922, United States

Location

University of Utah / Huntsman Cancer Institute SC-3

Salt Lake City, Utah, 84103, United States

Location

Novartis Investigative Site

Madrid, 28007, Spain

Location

Related Links

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; NVP-BKM120; Letrozole

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2014
• First Posted: June 3, 2014
• Study Start: June 27, 2014
• Primary Completion: October 26, 2016
• Study Completion: October 26, 2016
• Last Updated: December 19, 2020

Record last verified: 2018-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); ES (1)