A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1)

Early Breast Cancer Clinical Trial

— MONALEESA-1  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01919229
• Other study ID #: CLEE011A2201
• Secondary ID: 2013-002588-24
• Status: Terminated
• Phase: Phase 2
• First received: August 2, 2013
• Last updated: November 30, 2015
• Start date: October 2013
• Est. completion date: September 2014

Study information

• Verified date: November 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health Products (FAMPHP)Spain: The Spanish Agency of Medicines and Medical Devices (AEMPS)Italy: Italian Medicines Agency.
• Study type: Interventional

Clinical Trial Summary

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

Description:

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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

• 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.

• Systolic blood pressure >160 mmHg or <90 mmHg.

• Patient is currently receiving any of the following medications (see

Appendix 1 for details):

• That are known strong inducers or inhibitors of CYP3A4.

• That have a narrow therapeutic window and are predominantly metabolized through CYP3A4.

• That have a known risk to prolong the QT interval or induce Torsades de Pointes.

Other protocol-defined inclusion/exclusion criteria may apply

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Breast Neoplasms
• Early Breast Cancer

Intervention

Drug:
• LEE011 (ribociclib)
Ribociclib was supplied in 200 mg hard gelatin capsules for oral use.
• letrozole
Letrozole was supplied in 2.5mg tablets for oral use.

Locations

Country	Name	City	State
Singapore	Novartis Investigative Site	Singapore
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
United States	Massachusetts General Hospital SC-9	Boston	Massachusetts
United States	Highlands Oncology Group SC	Fayetteville	Arkansas
United States	University of Texas/MD Anderson Cancer Center Dept of MD Anderson (8)	Houston	Texas
United States	University of California at Los Angeles UCLA SC	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Singapore,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cell Cycle Response Rate Per Cell Proliferation Marker Ki67	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.	Day 1, Day15	No
Secondary	Safety and Tolerability of the Combination	Occurrence, frequency and severity of adverse events (AEs), laboratory abnormalities	Up to 30 days after the last dose	Yes
Secondary	Change From Baseline in Electrocardiogram (ECG) Parameters		Baseline, Day 14	Yes
Secondary	Change From Baseline in Expression of Retinoblastoma Protein (pRB)		Baseline, Day 15	No
Secondary	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	No
Secondary	Change in ECG Morphology		Baseline, Day 14	Yes
Secondary	Correlation Between PK Concentrations and ECG Changes	Correlation between the QTc interval change from baseline and plasma concentrations of LEE011 and/or any relevant metabolites	Day 14	Yes
Secondary	Change From Baseline in Expression of Cyclin-Dependent Kinase 1 (CDK1)		Baseline, Day 15	No