Clinical Trials/NCT01919229

NCT01919229

Terminated

Phase 2

A Randomized Pre-surgical Pharmacodynamics Study to Assess the Biological Activity of LEE011 Plus Letrozole Versus Single Agent Letrozole in Primary Breast Cancer

Novartis Pharmaceuticals5 sites in 2 countries14 target enrollmentOctober 2013

ConditionsEarly Breast Cancer

Interventionsletrozole LEE011 (ribociclib)

DrugsLEE011 (ribociclib)letrozole

Overview

Phase: Phase 2
Intervention: letrozole
Conditions: Early Breast Cancer
Sponsor: Novartis Pharmaceuticals
Enrollment: 14
Locations: 5
Primary Endpoint: Cell Cycle Response Rate Per Cell Proliferation Marker Ki67
Status: Terminated
Last Updated: 10 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multi-center, open-label Phase II randomized pre-surgical pharmacodynamics study.

Detailed Description

This randomized pre-surgical pharmacodynamics study will assess the biological activity of LEE011 plus letrozole versus single agent letrozole in primary breast cancer.

Registry

clinicaltrials.gov

Start Date

October 2013

End Date

September 2014

Last Updated

10 years ago

Study Type

Interventional

Study Design

Parallel

Sex

Female

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Female patient is ≥ 18 years old at the time of informed consent, with newly diagnosed resectable breast cancer, who received no prior therapy for breast cancer
•Patient is postmenopausal. Postmenopausal status is defined either by:
•Prior bilateral oophorectomy
•Age \<60 and amenorrhea for 12 or more months and FSH (Follicle Stimulating Hormone) and estradiol in the postmenopausal range.
•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 a grade II or grade III invasive breast cancer
•Patient has Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+ (if IHC 2+, a negative in situ hybridization (respectively FISH/CISH/SISH) test is required) by local laboratory testing
•Patient has at least one breast lesion with a diameter of ≥1.0 cm by the most accurate imaging modality used.
•Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria

•Patient has received any prior therapy for breast cancer.
•Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal cell skin cancer or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
•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 ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, Long QT Syndrome or conduction abnormality in the previous 12 months.
•Family history of QTc prolongation or of unexplainable sudden death at \<50 years of age.
•On screening 12 lead ECG, 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.

Arms & Interventions

Letrozole

Letrozole 2.5 mg alone once daily

Intervention: letrozole

LEE011 400 mg + letrozole

Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.

Intervention: LEE011 (ribociclib)

LEE011 400 mg + letrozole

Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily.

Intervention: letrozole

LEE011 600mg + letrozole

Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.

Intervention: LEE011 (ribociclib)

LEE011 600mg + letrozole

Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily.

Intervention: letrozole

Outcomes

Primary Outcomes

Cell Cycle Response Rate Per Cell Proliferation Marker Ki67

Time Frame: Day 1, Day15

Cell cycle response rate is defined by proportion of patients with natural logarithm of Ki-67 levels (expressed as percentage of baseline values) of less than 1 at the time of surgery. Since the trial was prematurely terminated, no statistical analysis was done.

Secondary Outcomes

Change From Baseline in Electrocardiogram (ECG) Parameters(Baseline, Day 14)
Safety and Tolerability of the Combination(Up to 30 days after the last dose)
Change From Baseline in Expression of Retinoblastoma Protein (pRB)(Baseline, Day 15)
PK (Pharmacokinetics) Parameters, Including But Not Limited to, Cmax, Tmax, AUClast for LEE011 (and Any Relevant Metabolites) and Letrozole.(Days 1, 8, 14 and 15)
Change in ECG Morphology(Baseline, Day 14)
Correlation Between PK Concentrations and ECG Changes(Day 14)
Change From Baseline in Expression of Cyclin-Dependent Kinase 1 (CDK1)(Baseline, Day 15)