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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02422615




Registration number
NCT02422615
Ethics application status
Date submitted
1/04/2015
Date registered
21/04/2015
Date last updated
1/06/2020

Titles & IDs
Public title
Study of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer.
Scientific title
A Randomized Double-blind, Placebo-controlled Study of Ribociclib in Combination With Fulvestrant for the Treatment of Men and Postmenopausal Women With Hormone Receptor Positive, HER2-negative, Advanced Breast Cancer Who Have Received no or Only One Line of Prior Endocrine Treatment
Secondary ID [1] 0 0
2015-000617-43
Secondary ID [2] 0 0
CLEE011F2301
Universal Trial Number (UTN)
Trial acronym
MONALEESA-3
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced 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 - fulvestrant
Treatment: Drugs - Ribociclib placebo

Experimental: Ribociclib + fulvestrant - Ribociclib 600mg daily oral (days 1 to 21 in a 28-day Cycle) in combination with fulvestrant 500mg i.m. injections every 28 days (Cycle n Day 1) with 1 additional dose on Day 15 of Cycle 1

Placebo Comparator: Ribociclib placebo + fulvestrant - Ribociclib placebo 600mg daily oral (days 1 to 21 in a 28-day Cycle) in combination with fulvestrant 500mg i.m. injections every 28 days (Cycle n Day 1) with 1 additional dose on Day 15 of Cycle 1


Treatment: Drugs: Ribociclib
Ribociclib 600mg daily oral (days 1 to 21 in a 28-day Cycle)

Treatment: Drugs: fulvestrant
Fulvestrant 500mg i.m. injections every 28 days (Cycle n Day 1) with 1 additional dose on Day 15 of Cycle 1

Treatment: Drugs: Ribociclib placebo
Ribociclib placebo 600mg daily oral (days 1 to 21 in a 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) Per Investigator Assessment - The primary endpoint of the study is PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a local radiology assessment according to RECIST 1.1
Timepoint [1] 0 0
Up to approximately 26 months
Secondary outcome [1] 0 0
Overall Survival (OS) - Time from date of randomization to the date of death from any cause.
Timepoint [1] 0 0
Up to approximately 58 months
Secondary outcome [2] 0 0
Progression Free Survival (PFS) Per Blinded Independent Review Committee (BICR) - The primary endpoint of the study is PFS, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. PFS will be assessed via a BICR according to RECIST 1.1
Timepoint [2] 0 0
Up to approximately 26 months
Secondary outcome [3] 0 0
Overall Response Rate (ORR) - Overall response rate (ORR) is defined as the proportion of patients with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1.
Timepoint [3] 0 0
Up to approximately 26 months
Secondary outcome [4] 0 0
Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score - Time to definitive deterioration of ECOG performance status in one category of score is defined as the time from the date of randomization to the date of event, which is defined as at least one score lower than the baseline.
Timepoint [4] 0 0
Up to approximately 26 months
Secondary outcome [5] 0 0
Safety and Tolerability of LEE011 - Safety will be determined by type, frequency and severity of adverse events per CTCAE version 4.03 and type, frequency and severity of laboratory toxicities per CTCAE version 4.03.
Timepoint [5] 0 0
Up to approximately 26 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 - The time to definitive 10% deterioration is defined as the time from the date of randomization to the date of event, which is defined as at least 10% relative to baseline worsening of the corresponding scale score (without further improvement above the threshold) or death due to any cause.
Timepoint [6] 0 0
Up to approximately 26 months
Secondary outcome [7] 0 0
Change From Baseline in the Global Health Status/QoL Scale Score of the EORTC QLQ-C30 - Change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized.
Timepoint [7] 0 0
Up to approximately 26 months
Secondary outcome [8] 0 0
Clinical Benefit Rate (CBR) - Clinical benefit rate (CBR), defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting 24 weeks or longer as defined in RECIST 1.1
Timepoint [8] 0 0
Up to approximately 26 months
Secondary outcome [9] 0 0
Time to Response (TTR) - Time from randomization to the first documented and confirmed response (complete response or partial response) as defined by RECIST 1.1
Timepoint [9] 0 0
Up to approximately 26 months
Secondary outcome [10] 0 0
Duration of Response (DOR) - Time from the first documented response (CR or PR) to the first documented progression or death due to underlying cancer as defined in RECIST 1.1
Timepoint [10] 0 0
Up to approximately 26 months

Eligibility
Key inclusion criteria
1. Patient is an adult male/female = 18 years old at the time of informed consent and has
signed informed consent before any trial related activities and according to local
guidelines. Female patients must be postmenopausal.

2. Patient has a histologically and/or cytologically confirmed diagnosis of
estrogen-receptor positive and/or progesterone receptor positive breast cancer by
local laboratory and has HER2-negative breast cancer.

3. Patient must have either measurable disease by RECIST 1.1 or at least one
predominantly lytic bone lesion.

4. Patient has advanced (loco regionally recurrent not amenable to curative therapy, e.g.
surgery and/or radiotherapy, or metastatic) breast cancer.

Patients may be:

- newly diagnosed advanced/metastatic breast cancer, treatment naïve

- relapsed with documented evidence of relapse more than 12 months from completion
of (neo)adjuvant endocrine therapy with no treatment for advanced/metastatic
disease

- relapsed with documented evidence of relapse on or within 12 months from
completion of (neo)adjuvant endocrine therapy with no treatment for
advanced/metastatic disease

- relapsed with documented evidence of relapse more than 12 months from completion
of adjuvant endocrine therapy and then subsequently progressed with documented
evidence of progression after one line of endocrine therapy (with either an
antiestrogen or an aromatase inhibitor) for advanced/metastatic disease

- newly diagnosed advanced/metastatic breast cancer at diagnosis that progressed
with documented evidence of progression after one line of endocrine therapy (with
either an antiestrogen or an aromatase inhibitor)

5. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

6. Patient has adequate bone marrow and organ function
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient with symptomatic visceral disease or any disease burden that makes the patient
ineligible for endocrine therapy per the investigator's best judgment.

2. Patient has received prior treatment with chemotherapy (except for neoadjuvant/
adjuvant chemotherapy), fulvestrant or any CDK4/6 inhibitor.

3. Patient with inflammatory breast cancer at screening .

4. Patient with CNS involvement unless they are at least 4 weeks from prior therapy
completion to starting the study treatment and have stable CNS tumor at the time of
screening and not receiving steroids and/or enzyme inducing anti-epileptic medications
for brain metastases

5. Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormality

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

- Known strong inducers or inhibitors of CYP3A4/5,

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

- Those have a narrow therapeutic window and are predominantly metabolized through
CYP3A4/5.

- Herbal preparations/medications, dietary supplements.

Other Protocol-defined Inclusion/Exclusion may apply.

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
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - St Leonards
Recruitment hospital [2] 0 0
Novartis Investigative Site - Herston
Recruitment hospital [3] 0 0
Novartis Investigative Site - East Melbourne
Recruitment hospital [4] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
3002 - East Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
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United States of America
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Alabama
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Istanbul
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Izmir
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Devon
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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-blind, placebo controlled study of ribociclib in
combination with fulvestrant for the treatment of postmenopausal women and men with hormone
receptor positive, Her2 negative, advanced breast cancer who have received no or only one
line of endocrine therapy for advanced breast cancer.
Trial website
https://clinicaltrials.gov/show/NCT02422615
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
Other publications