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

NCT01919229 | Terminated Phase 2 Results

• 2 other identifiers: CLEE011A22012013-002588-24
• Study Type: interventional
• Target: 14
• Locations: 3 countries
• Sites: 7

Brief Summary

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

Conditions

Early Breast Cancer

Keywords

HR-positive; HER2-negative; Breast cancer; LEE011; Letrozole; CDK; CDK4; CDK6; CDK4/6; Pharmacodynamics; Pre-surgical; Postmenopausal

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (7)

• Safety and Tolerability of the Combination

  Up to 30 days after the last dose

• Change From Baseline in Electrocardiogram (ECG) Parameters

  Baseline, Day 14

• 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

Study Arms (3)

Letrozole

ACTIVE COMPARATOR

Letrozole 2.5 mg alone once daily

Drug: letrozole

LEE011 400 mg + letrozole

EXPERIMENTAL

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

Drug: LEE011 (ribociclib); Drug: letrozole

LEE011 600mg + letrozole

EXPERIMENTAL

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

Drug: LEE011 (ribociclib); Drug: letrozole

Interventions

LEE011 (ribociclib) DRUG

Ribociclib was supplied in 200 mg hard gelatin capsules for oral use.

Also known as: ribociclib

LEE011 400 mg + letrozole; LEE011 600mg + letrozole

letrozole DRUG

Letrozole was supplied in 2.5mg tablets for oral use.

LEE011 400 mg + letrozole; LEE011 600mg + letrozole; Letrozole

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (7)

Highlands Oncology Group SC

Fayetteville, Arkansas, 72703, United States

Location

University of California at Los Angeles UCLA SC

Los Angeles, California, 90095, United States

Location

Massachusetts General Hospital SC-9

Boston, Massachusetts, 02114, United States

Location

University of Texas/MD Anderson Cancer Center Dept of MD Anderson (8)

Houston, Texas, 77030-4009, United States

Location

Novartis Investigative Site

Singapore, Singapore, 169610, Singapore

Location

Novartis Investigative Site

Barcelona, Catalonia, 08003, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Related Publications (1)

• Curigliano G, Gomez Pardo P, Meric-Bernstam F, Conte P, Lolkema MP, Beck JT, Bardia A, Martinez Garcia M, Penault-Llorca F, Dhuria S, Tang Z, Solovieff N, Miller M, Di Tomaso E, Hurvitz SA. Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study. Breast. 2016 Aug;28:191-8. doi: 10.1016/j.breast.2016.06.008. Epub 2016 Jun 20.

  PMID: 27336726 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

ribociclib; 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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2013
• First Posted: August 8, 2013
• Study Start: October 1, 2013
• Primary Completion: September 1, 2014
• Study Completion: September 1, 2014
• Last Updated: January 1, 2016
• Results First Posted: January 1, 2016

Record last verified: 2015-11

Locations

SG (1); ES (2); US (4)