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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01958021




Registration number
NCT01958021
Ethics application status
Date submitted
4/10/2013
Date registered
8/10/2013
Date last updated
26/04/2023

Titles & IDs
Public title
Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer.(MONALEESA-2)
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 - LEE011
Treatment: Drugs - Letrozole
Treatment: Drugs - LEE011 Placebo

Experimental: LEE011 + letrozole - LEE011 (Ribociclib) oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 QD + 2.5 mg letrozole QD

Placebo Comparator: Placebo + letrozole - Matching ribociclib placebo was the control drug and was administered orally once daily.


Treatment: Drugs: LEE011
Ribociclib was administered orally at a dose of 600 mg once daily (three 200 mg capsules).

Treatment: Drugs: Letrozole
Letrozole 2.5 mg tablets taken orally.

Treatment: Drugs: LEE011 Placebo
Matching ribociclib placebo was the control drug and was administered orally once daily.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS) Per Investigator Assessment
Timepoint [1] 0 0
Up to approximately 20 months
Secondary outcome [1] 0 0
Overall Response Rate (ORR) as Per Investigator Assessment
Timepoint [1] 0 0
Up to approximately 20 months
Secondary outcome [2] 0 0
Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 65 months
Secondary outcome [3] 0 0
Clinical Benefit Rate (CBR)
Timepoint [3] 0 0
Up to approximately 20 months
Secondary outcome [4] 0 0
Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score
Timepoint [4] 0 0
Up to approximately 20.5 months
Secondary outcome [5] 0 0
Safety and Tolerability of LEE011
Timepoint [5] 0 0
Up to approximately 21 months
Secondary outcome [6] 0 0
Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30
Timepoint [6] 0 0
Up to approximately 20 months
Secondary outcome [7] 0 0
QTc Interval
Timepoint [7] 0 0
Baseline, cycle 1 day 15, cycle 2 day 1, cycle 3 day 1, cycle 4 day 1, cycle 5 day 1, cycle 6 day 1, cycle 7 day 1, cycle 8 day 1, cycle 9 day 1

Eligibility
Key inclusion criteria
1. Women with advanced (locoregionally recurrent or metastatic) breast cancer not
amenable to curative therapy.

2. Patient is postmenopausal. Postmenopausal status is 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 Note: For women with therapy-induced
amenorrhea, serial measurements of FSH and/or estradiol are needed to ensure
postmenopausal status. Ovarian radiation or treatment with a luteinizing
hormone-releasing hormone agonist (LH-RHa) (goserelin acetate or leuprolide
acetate) is not permitted for induction of ovarian suppression in this trial.

3. No prior systemic anti-cancer therapy for advanced disease.

4. Patient has a histologically and/or cytologically confirmed diagnosis of
estrogen-receptor positive and/or progesterone receptor positive breast cancer by
local laboratory.

5. 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.

6. Patient must have 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 will
only be considered measurable if disease progression at the treated site after
completion of therapy is clearly documented).

OR

• If no measurable disease is present, then at least one predominantly lytic bone
lesion must be present (Patients with no measurable disease and only one predominantly
lytic bone lesion that has been previously irradiated are eligible if there is
documented evidence of disease progression of the bone lesion after irradiation).

7. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient who received any CDK4/6 inhibitor.

2. Patient who received any prior systemic anti-cancer therapy (including hormonal
therapy and chemotherapy) for advanced breast cancer

Note:

- Patients who received (neo) adjuvant therapy for breast cancer are eligible. If
the prior neo (adjuvant) therapy included letrozole or anastrozole the disease
free interval must be greater than 12 months from the completion of treatment
until randomization.

- Patients who received = 14 days of letrozole or anastrozole for advanced disease
prior to randomization are eligible.

- Any prior (neo) adjuvant anti-cancer therapy must be stopped at least 5
half-lives or 7 days, whichever is longer, before randomization

3. Patient is concurrently using other anti-cancer therapy.

4. Patient has 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. 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

6. Patient is currently receiving any of the following medications and cannot be
discontinued 7 days prior start if the treatment:

- 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.

- 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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Illinois
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Indiana
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Massachusetts
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PG
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PI
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RC
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Italy
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RM
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TO
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TR
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Italy
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VT
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Italy
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Napoli
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Gyeonggi Do
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Korea
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Russian Federation
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Arkhangelsk
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Russian Federation
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Nizhniy Novgorod
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Russian Federation
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Ryazan
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Singapore
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Gauteng
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Andalucia
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Cataluna
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Catalunya
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Comunidad Valenciana
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Galicia
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Madrid
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Sweden
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Eskilstuna
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Goteborg
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Joenkoeping
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Lund
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Sweden
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Uppsala
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Sweden
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Vaxjo
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Taiwan
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Taoyuan Taiwan ROC
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TWN
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Taiwan
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Kaohsiung
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Taipei
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Thailand
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Bangkok
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Ankara
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Diyarbakir
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Istanbul
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Izmir
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United Kingdom
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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
This is a multi-center, randomized, double-blinded, placebo controlled trial.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01958021
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01958021