Study of Efficacy and Safety of LEE011 in Postmenopausal Women With Advanced Breast Cancer.(MONALEESA-2)
Verified April 2015 by Novartis
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
First received: October 4, 2013
Last updated: April 30, 2015
Last verified: April 2015
This is a multi-center, randomized, double-blinded, placebo controlled trial.
Advanced, Metastatic Breast Cancer
Drug: LEE011 Placebo
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
||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
Primary Outcome Measures:
Secondary Outcome Measures:
- Overall survival (OS) [ Time Frame: Up to approximately 65 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 20 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 20 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 20.5 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 21 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 20 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, 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 ] [ 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:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||August 2017 (Final data collection date for primary outcome measure)
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
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: LEE011 Placebo
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.
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- Women with advanced (locoregionally recurrent or metastatic) breast cancer not amenable to curative therapy.
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.
- No prior systemic anti-cancer therapy for advanced disease.
- 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 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.
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).
• 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).
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Patient who received any CDK4/6 inhibitor.
Patient who received any prior systemic anti-cancer therapy (including hormonal therapy and chemotherapy) for advanced breast cancer
- 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
- Patient is concurrently using other anti-cancer therapy.
- 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.
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.
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For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01958021
|Contact: Novartis Pharmaceuticals
|Contact: Novartis Pharmaceuticals
No publications provided
||Novartis ( Novartis Pharmaceuticals )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||October 4, 2013
||April 30, 2015
||Argentina: The Argentinean Health Authority - ANMAT
Australia: Therapeutic Goods Administration - TGA
Austria: Austrian Agency for Health and Food Safety - AGES
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: Brazilian Health Surveillance Agency - ANVISA
Canada: Health Canada
Czech Republic: State Institute for Drug Control - SUKL
Denmark: Danish Health and Medicines Authority - DHMA
Finland: Finish Medicines Agency - FIMEA
France: National Agency for the Safety of Medicine and Health Products - ANSM
Germany: Federal Institute for Drugs and Medical Devices - BfArM
Hungary: National Institute of Pharmacy and Nutrition - OGYEI
Ireland: Health Products Regulatory Authority - HPRA
Israel: State of Israel Ministry of Health
Italy: Italian Medicines Agency - AIFA
Korea South: Ministry of Food and Drug Safety - MFDS
Lebanon: Lebanon - Ministry of Public Health
Netherlands: Medicines Evaluation Board
Norway: Norwegian Medicines Agency
Russia: Ministry of Healthcare of the Russian Federation
Singapore: Singapore - Ministry of Health
South Africa: South Africa Department of Health
Spain: Spanish Agency for Medicines and Health Products - AEMPS
Sweden: Medical Products Agency - MPA
Taiwan: Taiwan - Ministry of Health and Welfare
Thailand: Thailand Food and Drug Administration (FDA)
Turkey: Turkish Ministry of Health (Saglik Bakanligi)
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Keywords provided by Novartis:
Advanced breast cancer
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on May 29, 2015
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action