Clinical Research Directory

Browse clinical research sites, groups, and studies.

Sites Groups Studies

Back to Studies

ACTIVE NOT RECRUITING

NCT03701334

PHASE3

A Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as Adjuvant Treatment in Patients With HR+/HER2- Early Breast Cancer

Sponsor: Novartis Pharmaceuticals

View on ClinicalTrials.gov

Summary

A phase III, multicenter, randomized, open-label trial to evaluate the efficacy and safety of ribociclib with Endocrine Therapy (ET) as an adjuvant treatment in women and men with Hormone Receptor positive (HR+), Human Epidermal Growth Factor Receptor 2 negative (HER2-) Early Breast Cancer (EBC).

Official title: A Phase III Multi-center, Randomized, Open-label Trial to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negative Early Breast Cancer (New Adjuvant TriAl With Ribociclib [LEE011]: NATALEE)

Key Details

Gender

All

Age Range

18 Years - 100 Years

Study Type

INTERVENTIONAL

Enrollment

5101

Start Date

2018-12-07

Completion Date

2030-05-29

Last Updated

2026-04-01

Healthy Volunteers

Conditions

Early Breast Cancer

Interventions

DRUG

Ribociclib

Ribociclib orally taken at 400 mg on days 1 to 21 of a 28-day cycle

OTHER

Endocrine Therapy (ET)

Endocrine Therapy (ET) will be administered according to the local clinical guidelines and current local prescribing information

Inclusion Criteria 1. Signed and dated Patient Informed Consent Form (PICF) obtained prior to any trial-specific screening procedure. 2. Patient is ≥ 18 years-old at the time of PICF signature. 3. Patient is female with known menopausal status at the time of randomization or initiation of adjuvant ET (whichever occurs earlier), or male. Postmenopausal status is defined as: * Patient underwent bilateral oophorectomy, or * Age ≥ 60 years, or * Age \< 60 years and amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen, toremifene or ovarian suppression) and Follicle-stimulating hormone (FSH) and plasma estradiol are in the postmenopausal ranges per local normal ranges. * If taking tamoxifen or toremifene and age \<60 years, then FSH and plasma estradiol level in postmenopausal ranges. Notes * In women who are premenopausal at the beginning of adjuvant chemotherapy, amenorrhea is not a reliable indicator of menopausal status as ovarian function may still be intact or resume despite anovulation/amenorrhea. For these women with therapy-induced amenorrhea, serial measurements of FSH and/or estradiol per local clinical guidelines are required for determination of postmenopausal status. * All women who do not meet the criteria for postmenopausal status are considered premenopausal for the purpose of this trial. 4. Patient with histologically confirmed unilateral primary invasive adenocarcinoma of the breast with a date of initial cytologic or histologic diagnosis (i.e. date of the pathology report that confirmed the BC diagnosis) within 18 months prior to randomization. Patient with a multicentric and/or multifocal tumor is eligible if all histopathologically examined lesions meet the pathologic criteria in inclusion criteria 5 and 6. 5. Patient has breast cancer that is positive for ER and/or PgR according to the local laboratory as determined on the most recently analyzed tissue sample. 6. Patient has HER2-negative breast cancer defined as a negative in situ hybridization test or an immunohistochemistry (IHC) status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory). 7. Patient (except those enrolled in China) has available archival tumor tissue from the surgical specimen, for submission to a central laboratory (Note: in patients that underwent neoadjuvant systemic therapy and had a pathologic complete response, archival tumor tissue at the time of the initial diagnosis or before the administration of neoadjuvant therapy is mandatory). 8. Patient, after surgical resection where tumor was removed completely, with the final surgical specimen microscopic margins free from tumor, and belongs to one of the following categories: * Anatomic Stage Group III, or * Anatomic Stage Group IIB, or * Anatomic Stage Group IIA (subset) Notes: * For patients whose tumors are Anatomic Stage IIA, N0: * If Grade is 1 or unknown (Gx), patient is not eligible. * If Grade 2, the gene expression test results (by Oncotype DX, Prosigna/PAM50, MammaPrint or EndoPredict EPclin) or Ki67 levels should be used if obtained as per local practice (i.e. are not mandatory for the purpose of the trial). Results must be available at screening. * Patients that received neoadjuvant treatment must meet the above criteria (for stage, and if Stage IIA, N0, also for grade and Ki67 or gene expression test) in any presurgical staging/sample and/or in the surgical specimen. * Categorization into the AJCC 8th edition Anatomic Stage Groups requires determination of the T, N and M categories. ALND is the preferred method for axillary lymph node staging, however SLN dissection can be used to determine the N category in the following cases: * No metastasis in SLN (patient is considered as pN0). * Only micrometastasis in SLN (patient is considered as pN1mi). * Patients with T1-2 and no clinically-evident nodes prior to surgery, no neoadjuvant chemotherapy, at least one macrometastasis in 1 or 2 SLNs, no matted nodes or gross extranodal disease at the time of SLN dissection (patient is considered as pN1). In all other cases, ALND is required to determine the N category. 9. If indicated, patient has completed adjuvant and/or neoadjuvant chemotherapy according to the institutional guidelines, prior to screening. 10. If indicated, patient has completed adjuvant radiotherapy according to the institutional guidelines, prior to screening. 11. Patient has no contraindication for the adjuvant ET in the trial and is planned to be treated with ET for 5 years (since randomization date) or more. 12. Patient may have already received any standard neoadjuvant and/or adjuvant ET at the time of PICF signature, but randomization should occur within 12 months of the initial start date of ET. Ovarian suppression or short term ET for fertility preservation is not considered neoadjuvant/adjuvant ET. If patient was receiving tamoxifen or toremifene as adjuvant ET, a washout period of 5 half-lives (i.e. 35 days) prior to randomization is required (during that period patient can take AI). 13. Patient has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 14. Patient has adequate bone marrow and organ function as defined by the following local laboratory values: * Absolute neutrophil count (ANC) ≥ 1.5 × 109/L * Platelets ≥ 100 × 109/L * Hemoglobin ≥ 9.0 g/dL * Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) formula * Alanine transaminase (ALT) \< 2.5 × Upper Limit Normal (ULN) * Aspartate transaminase (AST) \< 2.5 × ULN * Total serum bilirubin \< ULN; or total bilirubin ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN in patients with well documented Gilbert's Syndrome * International normalized ratio (INR) ≤ 1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within 7 days prior to randomization) * Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements (the local laboratory value should be documented within normal limits after the correction) before randomization: * Potassium * Magnesium * Total Calcium (corrected for serum albumin) 15. Standard 12-lead ECG values assessed by a central laboratory, as: * QTcF interval (QT interval using Fridericia's correction) at screening \< 450 milliseconds (msec) * Resting heart rate 50-90 beats per minute (determined from the ECG) 16. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures. 17. Women of childbearing potential (CBP), defined as all women physiologically capable of becoming pregnant (see Inclusion Criterion #18 for additional information), must have confirmed negative serum pregnancy test (for β-hCG) within 14 days prior to randomization. 18. Women of CBP must be willing to use highly effective methods of contraception. Contraception must continue during the trial treatment and for 21 days after stopping the treatment. Highly effective contraception methods include: * Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking trial treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. * Male partner sterilization (at least 6 months prior to randomization). For female patients on the trial the vasectomized male partner should be the sole partner for that patient. If vasectomy of the male partner is the highly effective method of contraception chosen, the success of the vasectomy should be medically confirmed according to local practice. * Placement of an intrauterine device (IUD). Notes: * Use of oral (estrogen and progesterone), transdermal, injected, implanted, hormone containing intrauterine system or any other hormonal method of contraception is not allowed in this trial. * Women are considered of CBP unless: they have had ≥ 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (i.e. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy, or tubal ligation at least six weeks prior to randomization. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment she is considered not of CBP. * After the end of trial treatment, patients should use effective contraception according to local guidelines. Exclusion Criteria 1. Patient has received any CDK4/6 inhibitor. 2. Patient has received prior treatment with tamoxifen, raloxifene or AIs for reduction in risk ("chemoprevention") of breast cancer and/or treatment for osteoporosis within the last 2 years prior to randomization. Patient is concurrently using hormone replacement therapy. 3. Patient has received prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for doxorubicin, or 900 mg/m² or more for epirubicin. 4. Patient with a known hypersensitivity to any of the excipients of ribociclib and/or ET (e.g. rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, glucose-galactose malabsorption, and soy allergy). 5. Patient with distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) and/or evidence of recurrence after curative surgery. 6. Patient is concurrently using other anti-neoplastic therapy with the exception of adjuvant ET (see Inclusion Criterion #12). 7. Patient has had major surgery, chemotherapy or radiotherapy within 14 days prior to randomization. 8. Patient has not recovered from clinical and laboratory acute toxicities related to prior anti-cancer therapies to a NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.03 Grade ≤1 at day of randomization. Exceptions to this criterion: patients with any grade of alopecia, amenorrhea, grade 2 neuropathy are allowed to enter the trial or other toxicities not considered a safety risk for the patient as per Investigator's discretion, are allowed to enter the trial. 9. Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before randomization. Note: Patients with adequately treated, basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ are eligible. 10. Patient has known history of human immunodeficiency virus (HIV) infection (testing is not mandatory, unless required by local regulation). 11. Patient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (testing is not mandatory, unless required by local regulation). 12. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality, including any of the following: * History of documented myocardial infarction (MI), angina pectoris, symptomatic pericarditis, or coronary artery bypass graft within 6 months prior to trial entry. * Documented cardiomyopathy. * Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) (testing not mandatory) * Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following: * Risk factors for Torsades de Pointes (TdP) including uncorrected hypocalcemia, hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia. * Concomitant medication(s) with a known risk to prolong the QT interval and/or known to cause TdP that cannot be discontinued or replaced by safe alternative medication (e.g. within 5 half-lives or 7 days prior to starting trial treatment). * Inability to determine the QTcF interval. * Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade Atrioventricular (AV) block (e.g. bifascicular block, Mobitz type II and third degree AV block). * Uncontrolled arterial hypertension with systolic blood pressure \> 160 mmHg. 13. Patient is currently receiving any of the following substances within 7 days before randomization: * Concomitant medications, herbal supplements, and/or fruits (e.g. grapefruit, pummellos, starfruit, Seville oranges) and their juices that are known as strong inhibitors or inducers of CYP3A4/5 * Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5 14. Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting trial treatment, or has not fully recovered from side effects of such treatment. Note: The following uses of corticosteroids are permitted: a short duration (\<5 days) of systemic corticosteroids; any duration of topical applications (e.g. for rash), inhaled sprays (e.g. for obstructive airways diseases), eye drops or local injections (e.g. intra-articular). 15. Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the oral trial treatments (e.g. uncontrolled ulcerative diseases, uncontrolled nausea, vomiting or diarrhea, malabsorption syndrome, or small bowel resection). 16. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol (e.g. chronic pancreatitis, chronic active hepatitis, liver cirrhosis or any other significant liver disease, active untreated or uncontrolled fungal, bacterial or viral infections, active infection requiring systemic anti-bacterial therapy, etc.) or limit life expectancy to ≤5 years. 17. Participation in other studies involving investigational drug(s) within 30 days prior to randomization or within 5 half-lives of the investigational drug(s) (whichever is longer), or participation in any other type of medical research judged not to be scientifically or medically compatible with this trial. If the patient is enrolled or planned to be enrolled in another study that does not involve an investigational drug, the agreement of the Medical Monitor is required to establish eligibility. 18. Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial.

Locations (387)

University of Alabama at Birmingham-Kirklin Clinic

Birmingham, Alabama, United States

Cancer Treatment Centers of America

Goodyear, Arizona, United States

St Bernards Medical Center

Jonesboro, Arkansas, United States

Comprehensive Blood and Cancer

Bakersfield, California, United States

UCLA Beverly Hills

Beverly Hills, California, United States

UCLA Burbank

Burbank, California, United States

Encino Research Center

Encino, California, United States

St. Jude Heritage Medical Group

Fullerton, California, United States

UCLA Hematology Oncology

Laguna Hills, California, United States

Southern CA Oncology Rsrch Alliance

Los Angeles, California, United States

Stanford University Medical Center

Palo Alto, California, United States

UCLA Pasadena HC Hemato Onco

Pasadena, California, United States

UCLA Porter Ranch Hemato and Onco

Porter Ranch, California, United States

Cancer Care Associates Medical Grp

Redondo Beach, California, United States

Sharp Memorial Hospital

San Diego, California, United States

UCSF

San Francisco, California, United States

Central Coast Medical Oncology Corporation

Santa Maria, California, United States

UCLA Santa Monica Hematology Oncology

Santa Monica, California, United States

Lundquist Inst BioMed at Harbor

Torrance, California, United States

UCLA Valencia

Valencia, California, United States

Valley Breast Care

Van Nuys, California, United States

UCLA Cancer Center Westlake Village

Westlake Village, California, United States

University Of Colorado Hospital

Aurora, Colorado, United States

Rocky Mountain Cancer Centers

Denver, Colorado, United States

Hospital of Central Connecticut

New Britain, Connecticut, United States

Yale University School Of Medicine

New Haven, Connecticut, United States

Norwalk Hospital

Norwalk, Connecticut, United States

Eastern Connecticut Hematology and Oncology Associates

Norwich, Connecticut, United States

Holy Cross Hospital-Ft. Lauderdale

Fort Lauderdale, Florida, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Memorial Cancer Institute

Hollywood, Florida, United States

Baptist MD Anderson Cancer Center

Jacksonville, Florida, United States

University of Miami

Miami, Florida, United States

Orlando Health Clinical Trials

Orlando, Florida, United States

Florida Cancer Specialists-North

St. Petersburg, Florida, United States

Florida Cancer Specialists Pan

Tallahassee, Florida, United States

Florida Cancer Specialists

West Palm Beach, Florida, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Southeastern Regional Medical Center

Newnan, Georgia, United States

Cancer Treatment Centers of America

Zion, Illinois, United States

Cancer Care Center

New Albany, Indiana, United States

University of Kansas Cancer Center

Westwood, Kansas, United States

Cancer Center of Kansas

Wichita, Kansas, United States

Norton Cancer Institute

Louisville, Kentucky, United States

Mercy Medical Center

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan Cancer Center

Ann Arbor, Michigan, United States

Fairview Health Services

Maple Grove, Minnesota, United States

Metro Minnesota CCOP

Saint Louis Park, Minnesota, United States

Park Nicollet Institute

Saint Louis Park, Minnesota, United States

Saint Lukes Hospital of Kansas City

Kansas City, Missouri, United States

HCA Midwest Division

Kansas City, Missouri, United States

David C Pratt Cancer Center

St Louis, Missouri, United States

St Vincent Frontier Cancer Center

Billings, Montana, United States

Saint Francis Medical Center

Grand Island, Nebraska, United States

Comprehensive Cancer Cntr Of Nevada

Henderson, Nevada, United States

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Perlmutter Cancer Centre

New York, New York, United States

Randolph Medical Associates

Asheboro, North Carolina, United States

Cone Health Cancer Center

Greensboro, North Carolina, United States

Kaiser Permanente NW Region

Clackamas, Oregon, United States

Penn State Hershey Cancer Institute

Hershey, Pennsylvania, United States

Cancer Treatment Centers of America Eastern Regional Medical Center

Philadelphia, Pennsylvania, United States

The West Clinic

Germantown, Tennessee, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

Baylor Charles A Sammons Cancer Cnt

Dallas, Texas, United States

Ctr For Cancer And Blood Disorders

Fort Worth, Texas, United States

MD Anderson Cancer Center University of Texas

Houston, Texas, United States

Utah Cancer Specialists

Salt Lake City, Utah, United States

Virginia Cancer Specialists

Fairfax, Virginia, United States

Virginia Cancer Institute

Richmond, Virginia, United States

Fred Hutchinson Cancer Center

Seattle, Washington, United States

University of Wisconsin Paul P Carbone Comp Cancer Center

Madison, Wisconsin, United States

Novartis Investigative Site

San Salvador de Jujuy, Jujuy Province, Argentina

Novartis Investigative Site

Rosario, Santa Fe Province, Argentina

Novartis Investigative Site

Rosario, Sante Fe, Argentina

Novartis Investigative Site

San Miguel Tucuman, Tucumán Province, Argentina

Novartis Investigative Site

Rio Negro, Viedma, Argentina

Novartis Investigative Site

CABA, Argentina

Novartis Investigative Site

Córdoba, Argentina

Novartis Investigative Site

La Rioja, Argentina

Novartis Investigative Site

Campbelltown, New South Wales, Australia

Novartis Investigative Site

Coffs Harbour, New South Wales, Australia

Novartis Investigative Site

Darlinghurst, New South Wales, Australia

Novartis Investigative Site

Kingswood, New South Wales, Australia

Novartis Investigative Site

Kogarah, New South Wales, Australia

Novartis Investigative Site

North Ryde, New South Wales, Australia

Novartis Investigative Site

St Leonards, New South Wales, Australia

Novartis Investigative Site

Wahroonga, New South Wales, Australia

Novartis Investigative Site

Westmead, New South Wales, Australia

Novartis Investigative Site

Auchenflower, Queensland, Australia

Novartis Investigative Site

Birtinya, Queensland, Australia

Novartis Investigative Site

Wooloongabba, Queensland, Australia

Novartis Investigative Site

Bedford Park, South Australia, Australia

Novartis Investigative Site

Bendigo, Victoria, Australia

Novartis Investigative Site

East Melbourne, Victoria, Australia

Novartis Investigative Site

Epping, Victoria, Australia

Novartis Investigative Site

Fitzroy, Victoria, Australia

Novartis Investigative Site

Franston, Victoria, Australia

Novartis Investigative Site

Heidelberg, Victoria, Australia

Novartis Investigative Site

Melbourne, Victoria, Australia

Novartis Investigative Site

Shepparton, Victoria, Australia

Novartis Investigative Site

Murdoch, Western Australia, Australia

Novartis Investigative Site

Nedlands, Western Australia, Australia

Novartis Investigative Site

Liverpool, Australia

Novartis Investigative Site

Innsbruck, Tyrol, Austria

Novartis Investigative Site

Graz, Austria

Novartis Investigative Site

Linz, Austria

Novartis Investigative Site

Salzburg, Austria

Novartis Investigative Site

Vienna, Austria

Novartis Investigative Site

Hasselt, Limburg, Belgium

Novartis Investigative Site

Leuven, Vlaams Brabant, Belgium

Novartis Investigative Site

Brussels, Belgium

Novartis Investigative Site

Brussels, Belgium

Novartis Investigative Site

Charleroi, Belgium

Novartis Investigative Site

Edegem, Belgium

Novartis Investigative Site

Jette, Belgium

Novartis Investigative Site

Libramont, Belgium

Novartis Investigative Site

Liège, Belgium

Novartis Investigative Site

Namur, Belgium

Novartis Investigative Site

Wilrijk, Belgium

Novartis Investigative Site

Yvoir, Belgium

Novartis Investigative Site

Londrina, Paraná, Brazil

Novartis Investigative Site

Ijuí, Rio Grande do Sul, Brazil

Novartis Investigative Site