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Study of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer. (MONALEESA-3)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02422615
Recruitment Status : Active, not recruiting
First Posted : April 21, 2015
Results First Posted : September 19, 2018
Last Update Posted : April 16, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE April 1, 2015
First Posted Date  ICMJE April 21, 2015
Results First Submitted Date  ICMJE August 18, 2018
Results First Posted Date  ICMJE September 19, 2018
Last Update Posted Date April 16, 2019
Actual Study Start Date  ICMJE June 9, 2015
Actual Primary Completion Date November 3, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 18, 2018)
Progression Free Survival (PFS) Per Investigator Assessment [ Time Frame: Up to approximately 26 months ]
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
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2015)
Progression Free Survival (PFS) [ Time Frame: Up to approximately 26 months ]
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
Change History Complete list of historical versions of study NCT02422615 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 18, 2018)
  • Overall Survival (OS) [ Time Frame: Up to approximately 58 months ]
    Time from date of randomization to the date of death from any cause.
  • Progression Free Survival (PFS) Per Blinded Independant Review Committee (BICR) [ Time Frame: Up to approximately 26 months ]
    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
  • Overall Response Rate (ORR) [ Time Frame: Up to approximately 26 months ]
    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.
  • Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score [ Time Frame: Up to approximately 26 months ]
    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.
  • Safety and Tolerability of LEE011 [ Time Frame: Up to approximately 26 months ]
    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.
  • Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30 [ Time Frame: Up to approximately 26 months ]
    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.
  • Change From Baseline in the Global Health Status/QoL Scale Score of the EORTC QLQ-C30 [ Time Frame: Up to approximately 26 months ]
    Change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized.
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 26 months ]
    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
  • Time to Response (TTR) [ Time Frame: Up to approximately 26 months ]
    Time from randomization to the first documented and confirmed response (complete response or partial response) as defined by RECIST 1.1
  • Duration of Response (DOR) [ Time Frame: Up to approximately 26 months ]
    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
Original Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2015)
  • Overall Survival (OS) [ Time Frame: Up to approximately 58 months ]
    Time from date of randomization to the date of death from any cause.
  • Progression Free Survival (PFS) Per Blinded Independant Review Committee (BICR) [ Time Frame: Up to approximately 26 months ]
    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
  • Overall Response Rate (ORR) [ Time Frame: Up to approximately 26 months ]
    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.
  • Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score [ Time Frame: Up to approximately 26 months ]
    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.
  • 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. [ Time Frame: Up to approximately 26 months ]
    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.
  • Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30 [ Time Frame: Up to approximately 26 months ]
    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.
  • Change From Baseline in the Global Health Status/QoL Scale Score of the EORTC QLQ-C30 [ Time Frame: Up to approximately 26 months ]
    Change from baseline in the domain scores, health states, overall health status, and index values at the time of each assessment will be summarized.
  • Clinical benefit ratio (CBR) [ Time Frame: Up to approximately 26 months ]
    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
  • Time to Response (TTR) [ Time Frame: Up to approximately 26 months ]
    Time from randomization to the first documented and confirmed response (complete response or partial response as defined by RECIST 1.1
  • Duration of Response (DOR) [ Time Frame: Up to approximately 26 months ]
    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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer.
Official Title  ICMJE 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
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 positiv e, Her2 negative, advanced breast cancer who have received no or only one line of endocrine therapy for advanced breast cancer.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Advanced Breast Cancer
Intervention  ICMJE
  • Drug: Ribociclib
    Riblociclib 600mg daily oral (days 1 to 21 in a 28-day Cycle)
    Other Name: LEE011
  • Drug: fulvestrant
    Fulvestrant 500mg i.m. injections every 28 days (Cycle n Day 1) with 1 additional dose on Day 15 of Cycle 1
    Other Name: Faslodex
  • Drug: Ribociclib placebo
    Riblociclib placebo 600mg daily oral (days 1 to 21 in a 28-day Cycle)
    Other Name: LEE011 placebo
Study Arms  ICMJE
  • Experimental: Ribociclib + fulvestrant
    Riblociclib 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
    Interventions:
    • Drug: Ribociclib
    • Drug: fulvestrant
  • Placebo Comparator: Ribociclib placebo + fulvestrant
    Riblociclib 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
    Interventions:
    • Drug: fulvestrant
    • Drug: Ribociclib placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 4, 2019)
726
Original Estimated Enrollment  ICMJE
 (submitted: April 16, 2015)
660
Estimated Study Completion Date  ICMJE February 19, 2020
Actual Primary Completion Date November 3, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Bulgaria,   Canada,   Colombia,   Czechia,   Denmark,   France,   Germany,   Hungary,   Italy,   Jordan,   Korea, Republic of,   Lebanon,   Malaysia,   Mexico,   Netherlands,   Norway,   Poland,   Portugal,   Russian Federation,   Singapore,   Spain,   Sweden,   Switzerland,   Thailand,   Turkey,   United Kingdom,   United States
Removed Location Countries Brazil,   Czech Republic,   India
 
Administrative Information
NCT Number  ICMJE NCT02422615
Other Study ID Numbers  ICMJE CLEE011F2301
2015-000617-43 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP