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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01958021




Registration number
NCT01958021
Ethics application status
Date submitted
4/10/2013
Date registered
8/10/2013

Titles & IDs
Public title
Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer
Scientific title
A Randomized Double-blind, Placebo-controlled Study of LEE011 in Combination With Letrozole for the Treatment of Postmenopausal Women With Hormone Receptor Positive, HER2 Negative, Advanced Breast Cancer Who Received no Prior Therapy for Advanced Disease
Secondary ID [1] 0 0
2013-003084-61
Secondary ID [2] 0 0
CLEE011A2301
Universal Trial Number (UTN)
Trial acronym
MONALEESA-2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced, Metastatic Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ribociclib
Treatment: Drugs - Letrozole
Treatment: Drugs - Placebo

Experimental: Ribociclib+ letrozole - Ribociclib 600 mg daily oral (3 weeks on/ 1 week off) in combination with letrozole 2.5 mg daily oral

Placebo comparator: Placebo + letrozole - Placebo daily oral (3 weeks on/ 1 week off) in combination with letrozole 2.5 mg daily oral.

Participants were unblinded once the final OS analysis was completed and after the implementation of protocol amendment 10 (30-Apr-21) and were given the option to crossover to treatment with ribociclib + letrozole


Treatment: Drugs: Ribociclib
Ribociclib (600 mg, in three 200 mg hard gelatin capsules or tablets) was administered orally once daily on Days 1-21 of each 28-day cycle.

Treatment: Drugs: Letrozole
Letrozole (2.5 mg, tablets) was administered orally once daily on a continuous daily schedule (days 1-28 of each 28-day cycle)

Treatment: Drugs: Placebo
Placebo (hard gelatin capsules or tablets) was administered orally once daily on Days 1-21 of each 28-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) by Investigator Assessment
Timepoint [1] 0 0
Up to 23 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to approximately 87 months
Secondary outcome [2] 0 0
Overall Response Rate (ORR) by Investigator Assessment
Timepoint [2] 0 0
Up to 23 months
Secondary outcome [3] 0 0
Clinical Benefit Rate (CBR) by Investigator Assessment
Timepoint [3] 0 0
Up to 23 months
Secondary outcome [4] 0 0
Time to Definitive Deterioration of Eastern Cooperative Oncology Group Performance Status (ECOG PS) by at Least One Category of the Score
Timepoint [4] 0 0
From baseline up to 23 months
Secondary outcome [5] 0 0
Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (GHS/QoL) Scale Score of the European Organization for Research and Treatment of Cancer's Core Quality of Life Questionnaire (EORTC QLQ-C30)
Timepoint [5] 0 0
From baseline up to 23 months
Secondary outcome [6] 0 0
Change From Baseline in the GHS/QoL Scale Score of the EORTC QLQ-C30
Timepoint [6] 0 0
Baseline, every 2 cycles for 18 months, then every 3 cycles until last dose; at EOT (within 15 days from last dose);every 8 or 12 weeks post-treatment until progression (post-treatment efficacy visits), assessed up to 23 months. Cycle=28 days

Eligibility
Key inclusion criteria
Key

1. Women with advanced (locoregionally recurrent or metastatic) breast cancer that was not amenable to curative therapy.
2. The patient was postmenopausal. Postmenopausal status was defined either by:

* Prior bilateral oophorectomy
* Age =60
* Age <60 and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal range per local normal range.
3. There was no prior systemic anti-cancer therapy for advanced disease.
4. The patient had a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by the local laboratory.
5. The patient had HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC status of 0, 1+ or 2+. If IHC was 2+, a negative in situ hybridization (FISH, CISH, or SISH) test was required by local laboratory testing.
6. The patient must have had either:

Measurable disease, i.e., at least one measurable lesion as per RECIST 1.1 criteria (Tumor lesions previously irradiated or subjected to other locoregional therapy were considered measurable if disease progression at the treated site after completion of therapy was clearly documented). OR If no measurable disease was present, then at least one predominantly lytic bone lesion must have been present (Patients with no measurable disease and only one predominantly lytic bone lesion previously irradiated were eligible if there was documented evidence of disease progression of the bone lesion after irradiation).
7. The patient had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

Key
Minimum age
18 Years
Maximum age
100 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. The patient had received any CDK4/6 inhibitor.
2. The patient had received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer.

Note:
* Patients who had received (neo) adjuvant therapy for breast cancer were eligible. If the prior neo (adjuvant) therapy included letrozole or anastrozole, the disease-free interval had to be greater than 12 months from the completion of treatment until randomization.
* Patients who had received = 14 days of letrozole or anastrozole for advanced disease prior to randomization were eligible.
* Any prior (neo) adjuvant anti-cancer therapy had to be stopped at least 5 half-lives or 7 days, whichever was longer, before randomization.
3. The patient was concurrently using other anti-cancer therapy.
4. The patient had a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer.
5. The patient had 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.
* The patient had 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.
6. The patient was currently receiving any of the following medications and could not be discontinued 7 days prior to the start of treatment:

* Medications known to be strong inducers or inhibitors of CYP3A4.
* Medications known to have a risk of prolonging the QT interval or inducing Torsades de Pointes.
* Medications with a narrow therapeutic window and predominantly metabolized through CYP3A4.
* Herbal preparations/medications.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/12/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/03/2023
Sample size
Target
Accrual to date
Final
668
Recruitment in Australia
Recruitment state(s)
SA,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Kurralta Park
Recruitment hospital [2] 0 0
Novartis Investigative Site - East Melbourne
Recruitment hospital [3] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
5037 - Kurralta Park
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
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United States of America
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Arizona
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Arkansas
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Illinois
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Indiana
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Massachusetts
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Izmir
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Cornwall
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United Kingdom
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Newcastle upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01958021