Advanced, Metastatic Breast Cancer Clinical Trial
— MONALEESA-2Official 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
| Verified date | April 2023 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This is a multi-center, randomized, double-blinded, placebo controlled trial.
| Status | Completed |
| Enrollment | 668 |
| Est. completion date | March 16, 2023 |
| Est. primary completion date | January 29, 2016 |
| Accepts healthy volunteers | No |
| Gender | Female |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| Argentina | Novartis Investigative Site | Cordoba | |
| Argentina | Novartis Investigative Site | La Rioja | |
| Argentina | Novartis Investigative Site | San Miguel De Tucuman | Tucuman |
| Australia | Novartis Investigative Site | East Melbourne | Victoria |
| Australia | Novartis Investigative Site | Kurralta Park | South Australia |
| Australia | Novartis Investigative Site | Nedlands | Western Australia |
| Austria | Novartis Investigative Site | Salzburg | |
| Austria | Novartis Investigative Site | Vienna | |
| Austria | Novartis Investigative Site | Wien | |
| Belgium | Novartis Investigative Site | Hasselt | |
| Belgium | Novartis Investigative Site | Leuven | |
| Belgium | Novartis Investigative Site | Namur | |
| Belgium | Novartis Investigative Site | Sint Niklaas | Oost Vlaanderen |
| Belgium | Novartis Investigative Site | Wilrijk | |
| Brazil | Novartis Investigative Site | Ribeirao Preto | SP |
| Brazil | Novartis Investigative Site | Sao Paulo | SP |
| Brazil | Novartis Investigative Site | Sao Paulo | SP |
| Canada | Novartis Investigative Site | Burnaby | British Columbia |
| Canada | Novartis Investigative Site | Halifax | Nova Scotia |
| Canada | Novartis Investigative Site | Hamilton | Ontario |
| Canada | Novartis Investigative Site | Kitchener | Ontario |
| Canada | Novartis Investigative Site | Montreal | Quebec |
| Canada | Novartis Investigative Site | Ottawa | Ontario |
| Canada | Novartis Investigative Site | Quebec | |
| Canada | Novartis Investigative Site | Toronto | Ontario |
| Czechia | Novartis Investigative Site | Brno | Czech Republic |
| Czechia | Novartis Investigative Site | Brno Bohunice | Czech Republic |
| Czechia | Novartis Investigative Site | Liberec | Czech Republic |
| Czechia | Novartis Investigative Site | Olomouc | CZE |
| Denmark | Novartis Investigative Site | Aarhus | |
| Denmark | Novartis Investigative Site | Copenhagen | |
| Denmark | Novartis Investigative Site | Odense C | |
| Denmark | Novartis Investigative Site | Vejle | |
| Finland | Novartis Investigative Site | Helsinki | |
| Finland | Novartis Investigative Site | Turku | |
| France | Novartis Investigative Site | Angers Cedex 02 | |
| France | Novartis Investigative Site | Avignon Cedex | |
| France | Novartis Investigative Site | Besancon Cedex | |
| France | Novartis Investigative Site | Bordeaux Cedex | |
| France | Novartis Investigative Site | Creteil | |
| France | Novartis Investigative Site | Le Mans Cedex | |
| France | Novartis Investigative Site | Lyon Cedex | |
| France | Novartis Investigative Site | Nice Cedex 2 | Alpes Maritimes |
| France | Novartis Investigative Site | Pierre Benite Cedex | |
| France | Novartis Investigative Site | Rouen Cedex 1 | |
| France | Novartis Investigative Site | Saint-Herblain Cédex | |
| France | Novartis Investigative Site | Villejuif Cedex | Villejuif |
| Germany | Novartis Investigative Site | Aschaffenburg | |
| Germany | Novartis Investigative Site | Berlin | |
| Germany | Novartis Investigative Site | Berlin | |
| Germany | Novartis Investigative Site | Bielefeld | |
| Germany | Novartis Investigative Site | Bonn | |
| Germany | Novartis Investigative Site | Bottrop | |
| Germany | Novartis Investigative Site | Duesseldorf | |
| Germany | Novartis Investigative Site | Erlangen | |
| Germany | Novartis Investigative Site | Essen | |
| Germany | Novartis Investigative Site | Freiburg | |
| Germany | Novartis Investigative Site | Fuerth | |
| Germany | Novartis Investigative Site | Goslar | |
| Germany | Novartis Investigative Site | Heidelberg | |
| Germany | Novartis Investigative Site | Muenchen | |
| Germany | Novartis Investigative Site | Offenbach | |
| Germany | Novartis Investigative Site | Ravensburg | |
| Germany | Novartis Investigative Site | Recklinghausen | North Rhine-westphalia |
| Germany | Novartis Investigative Site | Tübingen | |
| Germany | Novartis Investigative Site | Ulm | |
| Germany | Novartis Investigative Site | Velbert | |
| Hungary | Novartis Investigative Site | Budapest | |
| Hungary | Novartis Investigative Site | Debrecen | |
| Hungary | Novartis Investigative Site | Gyor | |
| Hungary | Novartis Investigative Site | Gyula | |
| Ireland | Novartis Investigative Site | Cork | |
| Ireland | Novartis Investigative Site | Dublin 4 | |
| Israel | Novartis Investigative Site | Petach Tikva | |
| Israel | Novartis Investigative Site | Ramat Gan | |
| Israel | Novartis Investigative Site | Tel Aviv | |
| Italy | Novartis Investigative Site | Aviano | PN |
| Italy | Novartis Investigative Site | Brescia | BS |
| Italy | Novartis Investigative Site | Candiolo | TO |
| Italy | Novartis Investigative Site | Genova | GE |
| Italy | Novartis Investigative Site | Lecco | LC |
| Italy | Novartis Investigative Site | Macerata | MC |
| Italy | Novartis Investigative Site | Messina | ME |
| Italy | Novartis Investigative Site | Milano | MI |
| Italy | Novartis Investigative Site | Napoli | |
| Italy | Novartis Investigative Site | Padova | PD |
| Italy | Novartis Investigative Site | Perugia | PG |
| Italy | Novartis Investigative Site | Pisa | PI |
| Italy | Novartis Investigative Site | Reggio Calabria | RC |
| Italy | Novartis Investigative Site | Roma | RM |
| Italy | Novartis Investigative Site | Terni | TR |
| Italy | Novartis Investigative Site | Viterbo | VT |
| Korea, Republic of | Novartis Investigative Site | Bundang Gu | Gyeonggi Do |
| Korea, Republic of | Novartis Investigative Site | Gyeonggi do | Korea |
| Korea, Republic of | Novartis Investigative Site | Seoul | Korea |
| Korea, Republic of | Novartis Investigative Site | Seoul | |
| Korea, Republic of | Novartis Investigative Site | Seoul | |
| Lebanon | Novartis Investigative Site | Ashrafieh | |
| Lebanon | Novartis Investigative Site | Beirut | |
| Lebanon | Novartis Investigative Site | Beirut | |
| Lebanon | Novartis Investigative Site | Saida | |
| Netherlands | Novartis Investigative Site | Alkmaar | |
| Netherlands | Novartis Investigative Site | Amsterdam | |
| Netherlands | Novartis Investigative Site | Deventer | |
| Netherlands | Novartis Investigative Site | Groningen | |
| Netherlands | Novartis Investigative Site | Groningen | |
| Netherlands | Novartis Investigative Site | Leiden | |
| Netherlands | Novartis Investigative Site | Maastricht | AZ |
| Netherlands | Novartis Investigative Site | Sittard-Geleen | |
| Netherlands | Novartis Investigative Site | Tilburg | |
| Netherlands | Novartis Investigative Site | Zwolle | |
| Norway | Novartis Investigative Site | Bergen | |
| Norway | Novartis Investigative Site | Oslo | |
| Russian Federation | Novartis Investigative Site | Arkhangelsk | |
| Russian Federation | Novartis Investigative Site | Nizhniy Novgorod | |
| Russian Federation | Novartis Investigative Site | Ryazan | |
| Singapore | Novartis Investigative Site | Singapore | |
| South Africa | Novartis Investigative Site | Pretoria | Gauteng |
| Spain | Novartis Investigative Site | Barcelona | Cataluna |
| Spain | Novartis Investigative Site | Barcelona | Catalunya |
| Spain | Novartis Investigative Site | Hospitalet de LLobregat | Catalunya |
| Spain | Novartis Investigative Site | La Laguna | Santa Cruz De Tenerife |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Madrid | |
| Spain | Novartis Investigative Site | Malaga | Andalucia |
| Spain | Novartis Investigative Site | Santiago de Compostela | Galicia |
| Spain | Novartis Investigative Site | Sevilla | Andalucia |
| Spain | Novartis Investigative Site | Valencia | Comunidad Valenciana |
| Sweden | Novartis Investigative Site | Eskilstuna | |
| Sweden | Novartis Investigative Site | Goteborg | |
| Sweden | Novartis Investigative Site | Joenkoeping | |
| Sweden | Novartis Investigative Site | Lund | |
| Sweden | Novartis Investigative Site | Uppsala | |
| Sweden | Novartis Investigative Site | Vaxjo | |
| Taiwan | Novartis Investigative Site | Kaohsiung | |
| Taiwan | Novartis Investigative Site | Kuei Shan Chiang | Taoyuan Taiwan ROC |
| Taiwan | Novartis Investigative Site | New Taipei City | TWN |
| Taiwan | Novartis Investigative Site | Taipei | |
| Taiwan | Novartis Investigative Site | Taipei | |
| Thailand | Novartis Investigative Site | Bangkok | |
| Turkey | Novartis Investigative Site | Ankara | |
| Turkey | Novartis Investigative Site | Ankara | |
| Turkey | Novartis Investigative Site | Diyarbakir | |
| Turkey | Novartis Investigative Site | Istanbul | |
| Turkey | Novartis Investigative Site | Izmir | |
| United Kingdom | Novartis Investigative Site | Newcastle upon Tyne | |
| United Kingdom | Novartis Investigative Site | Truro | Cornwall |
| United States | Lehigh Valley Hospital Onc Dept | Allentown | Pennsylvania |
| United States | University of Colorado School of Medicine Onc Dept. | Aurora | Colorado |
| United States | Sidney Kimmel CCC at JH SC-3 | Baltimore | Maryland |
| United States | Texas Oncology, P.A. | Bedford | Texas |
| United States | Alta Bates Cancer Center Oncology Dept. | Berkeley | California |
| United States | Dana Farber Cancer Institute Dana Farber-9 | Boston | Massachusetts |
| United States | University Cancer Institute SC | Boynton Beach | Florida |
| United States | Hackensack Meridian Health | Brick | New Jersey |
| United States | Montefiore Medical Center SC-8 | Bronx | New York |
| United States | Cooper Cancer Center Cooper Cancer Center | Camden | New Jersey |
| United States | Ironwood Cancer and Research Centers SC | Chandler | Arizona |
| United States | Chattanooga Oncology and Hematology Associates PC Chattanooga Oncology | Chattanooga | Tennessee |
| United States | University of Chicago Dept. of Oncology | Chicago | Illinois |
| United States | University of Illinois Cancer Center at Chicago | Chicago | Illinois |
| United States | Oncology Hematology Care Inc Oncology Hematology Care (3) | Cincinnati | Ohio |
| United States | The Ohio State University Comprehensive Cancer Center Ohio State-2 | Columbus | Ohio |
| United States | Texas Oncology P A SC-3 | Dallas | Texas |
| United States | University of Texas Southwestern Medical Center | Dallas | Texas |
| United States | Florida Cancer Research Institute Dept of Oncology | Davie | Florida |
| United States | Georgia Cancer Specialists Georgia Cancer Spec | Decatur | Georgia |
| United States | City of Hope National Medical Center SC-5 | Duarte | California |
| United States | Duke University Medical Center SC-8 | Durham | North Carolina |
| United States | North Shore University Health System | Evanston | Illinois |
| United States | Providence Regional Cancer Partnership | Everett | Washington |
| United States | Virginia Cancer Specialists Fairfax Northern Virginia | Fairfax | Virginia |
| United States | Highlands Oncology Group | Fayetteville | Arkansas |
| United States | Florida Cancer Specialists FL Cancer Specialists | Fort Myers | Florida |
| United States | Center for Cancer and Blood Disorders SC | Fort Worth | Texas |
| United States | Texas Oncology, P.A. | Fort Worth | Texas |
| United States | Frederick Memorial Hospital SC | Frederick | Maryland |
| United States | Glendale-Adventist Medical Center Dept of Oncology | Glendale | California |
| United States | CR Wood Cancer Center | Glens Falls | New York |
| United States | Ingalls Memorial Hospital Ingalls Mem Hosp | Harvey | Illinois |
| United States | Penn State University Milton S Hershey Medical Center SC-3 | Hershey | Pennsylvania |
| United States | Memorial Hospital SC | Hollywood | Florida |
| United States | Moanalua Medical Center. Attn: Oncology Dept | Honolulu | Hawaii |
| United States | Millennium Research Clin Develop SC | Houston | Texas |
| United States | Texas Oncology Houston Memorial City SC | Houston | Texas |
| United States | University of Texas MD Anderson Cancer Center UT MDAnderson | Houston | Texas |
| United States | Indiana University Simon Cancer Center | Indianapolis | Indiana |
| United States | Jackson Oncology Associates | Jackson | Mississippi |
| United States | NEA Baptist Cancer Center | Jonesboro | Arkansas |
| United States | Saint Luke's Hospital/Marion Bloch Neuroscience Institute Oncology Dept | Kansas City | Missouri |
| United States | Rocky Mountain Cancer Centers RMCC - Aurora | Longmont | Colorado |
| United States | Cedars Sinai Medical Center SC-5 | Los Angeles | California |
| United States | The Angeles Clinic and Research Institute SC-3 | Los Angeles | California |
| United States | Dean Health System Onc Dept | Madison | Wisconsin |
| United States | Mercy Medical Research Institute SC-1 | Manchester | Missouri |
| United States | Texas Oncology | McAllen | Texas |
| United States | University of Miami Univ Miami 2 | Miami | Florida |
| United States | Winthrop University Hospital Onc Dept | Mineola | New York |
| United States | Virginia Piper Cancer Institute, Allina Health | Minneapolis | Minnesota |
| United States | Edward Hospital Dept of Oncology | Naperville | Illinois |
| United States | Foundation Medical Partners | Nashua | New Hampshire |
| United States | Sarah Cannon Research Institute SC-2 | Nashville | Tennessee |
| United States | Vanderbilt University Medical Center SC-4 | Nashville | Tennessee |
| United States | Cancer Institute of New Jersey Onc Dept | New Brunswick | New Jersey |
| United States | Mount Sinai School of Medicine SC | New York | New York |
| United States | NYU Langone Medical Center CV Research center SC-2 | New York | New York |
| United States | Mercy Clinic Oklahoma Communities Mercy Oncology | Oklahoma City | Oklahoma |
| United States | Florida Retina Institute SC-3 | Orlando | Florida |
| United States | Florida Retina Institute SC-5 | Orlando | Florida |
| United States | Sacred Heart Medical Oncology SC | Pensacola | Florida |
| United States | Richardson Hematology Oncology Associates | Richardson | Texas |
| United States | UC Davis Comprehensive Cancer Center SC-2 | Sacramento | California |
| United States | Florida Cancer Specialists-North | Saint Petersburg | Florida |
| United States | Oncology and Hematology Associates of Southwest Virginia Inc | Salem | Virginia |
| United States | Utah Cancer Specialists Utah Cancer Specialists (11) | Salt Lake City | Utah |
| United States | Texas Oncology P A | San Antonio | Texas |
| United States | Arizona Oncology Associates PC HAL | Sedona | Arizona |
| United States | Avera Cancer SC-2 | Sioux Falls | South Dakota |
| United States | Northwest Medical Specialties Dept of Onc | Tacoma | Washington |
| United States | Lewis Hall Singletary Onc Ctr at John D. Archbold Mem Hosp. Onc Dept | Thomasville | Georgia |
| United States | Texas Oncology Northeast Texas | Tyler | Texas |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, Argentina, Australia, Austria, Belgium, Brazil, Canada, Czechia, Denmark, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Korea, Republic of, Lebanon, Netherlands, Norway, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Progression Free Survival (PFS) Per Investigator Assessment | 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 | Up to approximately 20 months | |
| Secondary | Overall Response Rate (ORR) as Per Investigator Assessment | 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. | Up to approximately 20 months | |
| Secondary | Overall Survival (OS) | Time from date of randomization to the date of death from any cause. | Up to approximately 65 months | |
| Secondary | Clinical Benefit Rate (CBR) | 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. | Up to approximately 20 months | |
| Secondary | Time to Definitive Deterioration of ECOG Performance Status in One Category of the Score | 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. | Up to approximately 20.5 months | |
| Secondary | Safety and Tolerability of LEE011 | 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. | Up to approximately 21 months | |
| Secondary | Time to Definitive 10% Deterioration in the Global Health Status/Quality of Life (QOL) Scale Score of the EORTC QLQ-C30 | 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. | Up to approximately 20 months | |
| Secondary | QTc Interval | Time between the start of the Q wave and the end of the T wave corrected for heart rate | 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 |