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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 : Completed
First Posted : April 21, 2015
Results First Posted : September 19, 2018
Last Update Posted : May 23, 2023
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Breast Cancer Drug: Ribociclib Drug: fulvestrant Drug: Ribociclib placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 726 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : June 9, 2015
Actual Primary Completion Date : November 3, 2017
Actual Study Completion Date : January 11, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arms and Interventions
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Arm Intervention/treatment
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
 Drug: Ribociclib
Ribociclib 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
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
 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
Ribociclib placebo 600mg daily oral (days 1 to 21 in a 28-day Cycle)
Other Name: LEE011 placebo


Outcome Measures
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Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to approximately 58 months ]
    Time from date of randomization to the date of death from any cause.

  2. Progression Free Survival (PFS) Per Blinded Independent 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02422615


Locations
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Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Study Protocol  [PDF] July 28, 2016
Statistical Analysis Plan  [PDF] October 11, 2017

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02422615    
Other Study ID Numbers: CLEE011F2301
2015-000617-43 ( EudraCT Number )
First Posted: April 21, 2015    Key Record Dates
Results First Posted: September 19, 2018
Last Update Posted: May 23, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
HR-positive
HER2-negative
Advanced breast cancer
LEE011
ribociclib
fulvestrant
faslodex
CDK
CDK4
CDK6
CDK4/6
CDK4/6 inhibitor
Phase III
ER-positive
PR-positive
 Postmenopausal
Men
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Use
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Fulvestrant
Antineoplastic Agents, Hormonal
 Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs