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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01958021
First received: October 4, 2013
Last updated: October 8, 2014
Last verified: October 2014
  Purpose

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


Condition Intervention Phase
Advanced, Metastatic Breast Cancer
Drug: LEE011
Drug: Letrozole
Drug: LEE011 Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: Up to approximatly 25 months ] [ Designated as safety issue: No ]
    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:
  • Overall survival (OS) [ Time Frame: Up to approximately 69 months ] [ Designated as safety issue: No ]
    Time from date of randomization to the date of death from any cause.

  • Overall response rate (ORR) [ Time Frame: Up to approximately 25 months ] [ Designated as safety issue: No ]
    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.

  • Clinical benefit rate (CBR) [ Time Frame: Up to approximately 25 months ] [ Designated as safety issue: No ]
    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.

  • Time to definitive deterioration of ECOG performance status in one category of the score [ Time Frame: Up to approximately 25.5 months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 25 months ] [ Designated as safety issue: No ]
    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.

  • QTc interval [ Time Frame: Baseline, cycle 1 day 15, cycle 2 day 1 and cycle 3 day 1 ] [ Designated as safety issue: Yes ]
    Time between the start of the Q wave and the end of the T wave corrected for heart rate


Estimated Enrollment: 500
Study Start Date: December 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LEE011 + letrozole
LEE011 oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 600mg LEE011 QD + 2.5 mg letrozole QD
Drug: LEE011 Drug: Letrozole
Placebo Comparator: Placebo + letrozole
Placebo oral (3 weeks on/ 1 week off) in combination with oral once daily letrozole. 2.5 mg letrozole QD + placebo
Drug: Letrozole Drug: LEE011 Placebo

Detailed Description:

The purpose of this study is 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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01958021

Contacts
Contact: Novartis Pharmaceuticals 1-888-669-6682
Contact: Novartis Pharmaceuticals

  Show 361 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01958021     History of Changes
Other Study ID Numbers: CLEE011A2301, 2013-003084-61
Study First Received: October 4, 2013
Last Updated: October 8, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
HR-positive
HER2-negative
Advanced breast cancer
LEE011
Letrozole
CDK
CDK4
CDK6
CDK4/6
Phase III
ER-positive
PR-positive
Postmenopausal

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Letrozole
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014