Clinical Trials /

Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer.(MONALEESA-2)

NCT01958021

Description:

This is a multi-center, randomized, double-blinded, placebo controlled trial.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer.(MONALEESA-2)
  • Official 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

Clinical Trial IDs

  • ORG STUDY ID: CLEE011A2301
  • SECONDARY ID: 2013-003084-61
  • NCT ID: NCT01958021

Conditions

  • Advanced, Metastatic Breast Cancer

Interventions

DrugSynonymsArms
LEE011LEE011 + letrozole
LetrozoleLEE011 + letrozole
LEE011 PlaceboPlacebo + letrozole

Purpose

This is a multi-center, randomized, double-blinded, placebo controlled trial.

Detailed Description

      The primary purpose of this study was to assess the efficacy of LEE011, as measured by
      progression free survival (PFS), in postmenopausal women with HR positive, HER2 negative
      advanced breast cancer who received no prior treatment for advanced disease.
    

Trial Arms

NameTypeDescriptionInterventions
LEE011 + letrozoleExperimentalLEE011 (Ribociclib) oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 QD + 2.5 mg letrozole QD
  • LEE011
  • Letrozole
Placebo + letrozolePlacebo ComparatorMatching ribociclib placebo was the control drug and was administered orally once daily.
  • Letrozole
  • LEE011 Placebo

Eligibility Criteria

        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

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival (PFS) Per Investigator Assessment
Time Frame:Up to approximately 20 months
Safety Issue:
Description: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 was assessed via a local radiology assessment according to RECIST 1.1

Secondary Outcome Measures

Measure:Overall Response Rate (ORR) as Per Investigator Assessment
Time Frame:Up to approximately 20 months
Safety Issue:
Description: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. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Measure:Overall Survival (OS)
Time Frame:Up to approximately 65 months
Safety Issue:
Description:Time from date of randomization to the date of death from any cause.
Measure:Clinical Benefit Rate (CBR)
Time Frame:Up to approximately 20 months
Safety Issue:
Description:Clinical Benefit Rate (CBR) is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) lasting more than 24 weeks as defined in RECIST 1.1.
Measure:Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score
Time Frame:Up to approximately 20.5 months
Safety Issue:
Description: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.
Measure:Safety and Tolerability of LEE011
Time Frame:Up to approximately 21 months
Safety Issue:
Description: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.
Measure: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 20 months
Safety Issue:
Description: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.
Measure:QTc Interval
Time Frame: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
Safety Issue:
Description:Time between the start of the Q wave and the end of the T wave corrected for heart rate

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Novartis Pharmaceuticals

Trial Keywords

  • HR-positive
  • HER2-negative
  • Advanced breast cancer
  • LEE011
  • Letrozole
  • CDK
  • CDK4
  • CDK6
  • CDK4/6
  • Phase III
  • ER-positive
  • PR-positive
  • Postmenopausal

Last Updated

May 24, 2017