Early Breast CancerPhase 2MONALEESA-1NCT01919229
A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1)
A Phase 2 study testing LEE011 (ribociclib) and letrozole in people with Early Breast Cancer, run by Novartis Pharmaceuticals at 7 sites in 3 countries.
Trial summary
This is a multi-center, open-label Phase II randomized pre-surgical pharmacodynamics study. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Early Breast Cancer
- What is being tested?
- LEE011 (ribociclib) and letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 7 sitesin 3 countries
- Study dates
- Oct 2013to Sep 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female patient is ≥ 18 years old at the time of informed consent, with newly diagnosed resectable breast cancer, who received no prior therapy for breast cancer
- Patient is postmenopausal. Postmenopausal status is defined either by:
- Prior bilateral oophorectomy
- Age ≥60
- Age <60 and amenorrhea for 12 or more months and FSH (Follicle Stimulating Hormone) and estradiol in the postmenopausal range.
- Patient has a histologically (and/or cytologically) confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
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- Patient has a grade II or grade III invasive breast cancer
- Patient has Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+ (if IHC 2+, a negative in situ hybridization (respectively FISH/CISH/SISH) test is required) by local laboratory testing
- Patient has at least one breast lesion with a diameter of ≥1.0 cm by the most accurate imaging modality used.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Who cannot join
- Patient has received any prior therapy for breast cancer.
- Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal cell skin cancer or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
- 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
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- Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
- History of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, Long QT Syndrome or conduction abnormality in the previous 12 months.
- Family history of QTc prolongation or of unexplainable sudden death at <50 years of age.
- On screening 12 lead ECG, 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 mmHg or <90 mmHg.
- Patient is currently receiving any of the following medications (see
- Appendix 1 for details):
- That are known strong inducers or inhibitors of CYP3A4.
- That have a narrow therapeutic window and are predominantly metabolized through CYP3A4.
- That have a known risk to prolong the QT interval or induce Torsades de Pointes.
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
United States4 sites
Massachusetts General Hospital SC-9
Boston, Massachusetts, 02114
Highlands Oncology Group SC
Fayetteville, Arkansas, 72703
University of Texas/MD Anderson Cancer Center Dept of MD Anderson (8)
Houston, Texas, 77030-4009
University of California at Los Angeles UCLA SC
Los Angeles, California, 90095
Spain2 sites
Novartis Investigative Site
Barcelona, Catalonia, 08003
Novartis Investigative Site
Barcelona, Catalonia, 08035
About this study
Official title: A Randomized Pre-surgical Pharmacodynamics Study to Assess the Biological Activity of LEE011 Plus Letrozole Versus Single Agent Letrozole in Primary Breast Cancer
This is a multi-center, open-label Phase II randomized pre-surgical pharmacodynamics study.
Read the detailed description
This randomized pre-surgical pharmacodynamics study will assess the biological activity of LEE011 plus letrozole versus single agent letrozole in primary breast cancer.
- Conditions
- Early Breast Cancer
- Being tested
- LEE011 (ribociclib), letrozole
- Keywords
- HR-positive, HER2-negative, Breast cancer, LEE011, Letrozole, CDK, CDK4, CDK6, CDK4/6, Pharmacodynamics, Pre-surgical, Postmenopausal
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LEE011 (ribociclib)Drug
Also called ribociclib
Ribociclib was supplied in 200 mg hard gelatin capsules for oral use.
letrozoleDrug
Letrozole was supplied in 2.5mg tablets for oral use.
| Study group | Role | What they receive |
|---|---|---|
| Letrozole | Active comparator | Letrozole 2.5 mg alone once daily Receives: Drug: letrozole |
| LEE011 400 mg + letrozole | Experimental | Letrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily. Receives: Drug: LEE011 (ribociclib); Drug: letrozole |
| LEE011 600mg + letrozole | Experimental | Letrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily. Receives: Drug: LEE011 (ribociclib); Drug: letrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cell Cycle Response Rate Per Cell Proliferation Marker Ki67
Cell cycle response rate is defined by proportion of patients with natural logarithm of Ki-67 levels (expressed as percentage of baseline values) of less than 1 at the time of surgery. Since the trial was prematurely terminated, no statistical analysis was done.
Measured: Day 1, Day15
Secondary outcomes (7)
Safety and Tolerability of the Combination
Occurrence, frequency and severity of adverse events (AEs), laboratory abnormalities
Measured: Up to 30 days after the last dose
Change From Baseline in Electrocardiogram (ECG) Parameters
Measured: Baseline, Day 14
Change From Baseline in Expression of Retinoblastoma Protein (pRB)
Measured: Baseline, Day 15
PK (Pharmacokinetics) Parameters, Including But Not Limited to, Cmax, Tmax, AUClast for LEE011 (and Any Relevant Metabolites) and Letrozole.
Measured: Days 1, 8, 14 and 15
Change in ECG Morphology
Measured: Baseline, Day 14
Correlation Between PK Concentrations and ECG Changes
Correlation between the QTc interval change from baseline and plasma concentrations of LEE011 and/or any relevant metabolites
Measured: Day 14
Change From Baseline in Expression of Cyclin-Dependent Kinase 1 (CDK1)
Measured: Baseline, Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2013 (estimated)
- Study startOct 2013
- Primary completionSep 2014
- Study completionSep 2014
Why it stopped: Due to low recruitment, it was decided to terminate the study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Early Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01919229
- Sponsor's protocol ID
- CLEE011A2201
- Other IDs
- 2013-002588-24
- Acronym
- MONALEESA-1
- Status last verified
- Nov 2015
- First submitted
- 2 Aug 2013
- Last updated
- 1 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Curigliano G, Gomez Pardo P, Meric-Bernstam F, Conte P, Lolkema MP, Beck JT, Bardia A, Martinez Garcia M, Penault-Llorca F, Dhuria S, Tang Z, Solovieff N, Miller M, Di Tomaso E, Hurvitz SA. Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study. Breast. 2016 Aug;28:191-8. doi: 10.1016/j.breast.2016.06.008. Epub 2016 Jun 20.
PubMed 27336726
Study at a glance
From the registry record, last updated by the sponsor on 1 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Pre-surgical Pharmacodynamics Study to Assess the Biological Activity of LEE011 Plus Letrozole Versus Single Agent Letrozole in Primary Breast Cancer
- ClinicalTrials.gov ID
- NCT01919229
- Acronym / sponsor ID
- MONALEESA-1 / CLEE011A2201
- Conditions
- Early Breast Cancer
- Keywords
- HR-positive, HER2-negative, Breast cancer, LEE011, Letrozole, CDK, CDK4, CDK6
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to low recruitment, it was decided to terminate the study.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 8 Aug 2013 (estimated)
- Results
- Posted 1 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center, open-label Phase II randomized pre-surgical pharmacodynamics study.
Detailed description
This randomized pre-surgical pharmacodynamics study will assess the biological activity of LEE011 plus letrozole versus single agent letrozole in primary breast cancer.
Study design
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Letrozole | Active comparator | Drug: letrozoleLetrozole 2.5 mg alone once daily |
| LEE011 400 mg + letrozole | Experimental | Drug: LEE011 (ribociclib), Drug: letrozoleLetrozole 2.5 mg once daily and ribociclib 400 mg (2 capsules of 200 mg each) once daily. |
| LEE011 600mg + letrozole | Experimental | Drug: LEE011 (ribociclib), Drug: letrozoleLetrozole 2.5 mg once daily and ribociclib 600 mg (3 capsules of 200 mg each) once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Female patient is ≥ 18 years old at the time of informed consent, with newly diagnosed resectable breast cancer, who received no prior therapy for breast cancer
- Patient is postmenopausal. Postmenopausal status is defined either by:
- Patient has a histologically (and/or cytologically) confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory.
- Patient has a grade II or grade III invasive breast cancer
- Patient has Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer defined as a negative in situ hybridization test or an Immunohistochemistry (IHC) status of 0, 1+ or 2+ (if IHC 2+, a negative in situ hybridization (respectively FISH/CISH/SISH) test is required) by local laboratory testing
Key exclusion criteria (17 listed)
- Patient has received any prior therapy for breast cancer.
- Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal cell skin cancer or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.
- Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:
- Patient is currently receiving any of the following medications (see
- That are known strong inducers or inhibitors of CYP3A4.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LEE011 (ribociclib)Also: ribociclibRibociclib was supplied in 200 mg hard gelatin capsules for oral use. | Drug | LEE011 400 mg + letrozole, LEE011 600mg + letrozole |
| letrozoleLetrozole was supplied in 2.5mg tablets for oral use. | Drug | LEE011 400 mg + letrozole, LEE011 600mg + letrozole, Letrozole |
Primary outcome
Cell Cycle Response Rate Per Cell Proliferation Marker Ki67
Time frame: Day 1, Day15
Cell cycle response rate is defined by proportion of patients with natural logarithm of Ki-67 levels (expressed as percentage of baseline values) of less than 1 at the time of surgery. Since the trial was prematurely terminated, no statistical analysis was done.
7 secondary outcomes
Safety and Tolerability of the Combination
Time frame: Up to 30 days after the last dose
Change From Baseline in Electrocardiogram (ECG) Parameters
Time frame: Baseline, Day 14
Change From Baseline in Expression of Retinoblastoma Protein (pRB)
Time frame: Baseline, Day 15
PK (Pharmacokinetics) Parameters, Including But Not Limited to, Cmax, Tmax, AUClast for LEE011 (and Any Relevant Metabolites) and Letrozole.
Time frame: Days 1, 8, 14 and 15
Change in ECG Morphology
Time frame: Baseline, Day 14
Correlation Between PK Concentrations and ECG Changes
Time frame: Day 14
Change From Baseline in Expression of Cyclin-Dependent Kinase 1 (CDK1)
Time frame: Baseline, Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27336726Curigliano G, Gomez Pardo P, Meric-Bernstam F, Conte P, Lolkema MP, Beck JT, Bardia A, Martinez Garcia M, Penault-Llorca F, Dhuria S, Tang Z, Solovieff N, Miller M, Di Tomaso E, Hurvitz SA. Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study. Breast. 2016 Aug;28:191-8. doi: 10.1016/j.breast.2016.06.008. Epub 2016 Jun 20.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing LEE011 (ribociclib) and letrozole in people with Early Breast Cancer, run by Novartis Pharmaceuticals at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 1 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Spain, Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cell Cycle Response Rate Per Cell Proliferation Marker Ki67 (time frame: Day 1, Day15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01919229, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jan 2016.