Ribociclib Given Concurrently with Postoperative Radiation Therapy for the Treatment of Patients with High-Risk, Node Positive, Hormone Receptor Positive, HER2 Negative Breast Cancer

Inclusion Criteria

• Women with estrogen receptor (ER)-positive (≥ 1% positivity as determined by local pathology laboratory), HER2-negative breast cancer with ≥ 4 lymph nodes involved on sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND) OR have between 1-3 lymph nodes involved AND at least one of the following high-risk features: * T3 tumor * Grade 3 tumor * Ki-67 ≥ 20%
• Age ≥ 18
• Patients must have undergone gross total excision of all locoregional disease with negative margins (i.e., no tumor on ink). At least 21 days must elapse between surgical treatment for breast cancer and initiation of study treatment
• Patients must have completed chemotherapy (either in neoadjuvant or adjuvant setting). If received adjuvant chemotherapy, chemotherapy must have completed at least 21 days prior to initiation of study treatment
• Participants must have recovered (grade ≤ 1) from the acute effects of chemotherapy and surgical side effects following definitive breast surgery except for neuropathy and alopecia
• Absolute neutrophil count ≥ 1.5 × 10^9/L (as assessed within 2 weeks [14 days] of study enrollment by central laboratory)
• Platelets ≥ 100 × 10^9/L (as assessed within 2 weeks [14 days] of study enrollment by central laboratory)
• Hemoglobin ≥ 9.0 g/dL (as assessed within 2 weeks [14 days] of study enrollment by central laboratory)
• 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 the first dose of study drug) (as assessed within 2 weeks [14 days] of study enrollment)
• Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 according to the Modification of Diet in Renal Disease (MDRD) formula (as assessed within 2 weeks [14 days] of study enrollment)
• Total bilirubin < upper limit of normal (ULN) except for patients with Gilbert’s syndrome who may only be included if the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN (as assessed within 2 weeks [14 days] of study enrollment)
• Patient must have the following laboratory values within normal limits or corrected to within normal limits with supplements as measured within 2 weeks (14 days) of study enrollment: * Potassium * Magnesium * Total calcium (corrected for serum albumin)
• Fridericia's corrected QT interval (QTcF) interval at screening electrocardiogram (EKG) ≤ 450ms (QT interval using Fridericia’s correction)
• Mean resting heart rate 50-90 bpm (determined from the EKG)
• Ability to swallow study drug (ribociclib)
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky > 60%)
• Ability to read and understand English and willingness to sign informed consent
• Women of childbearing potential must have confirmed negative pregnancy test (urine or serum) within 14 days of initiation of study treatment and be willing to use adequate contraception (i.e., barrier method, non-hormonal intra-uterine device) for birth control. Receipt of ovarian function suppression as a part of breast cancer therapy is considered an adequate form of contraception

Exclusion Criteria

• Prior history of radiation therapy to the chest wall and/or regional nodes is not allowed (but prior radiation therapy to other sites is permissible)
• Prior history of any CDK4/6 inhibitor therapy
• Patients who are pregnant or breastfeeding. Because radiation is known to be teratogenic, women of childbearing potential must have a documented negative pregnancy test performed prior to the start of study therapy. Participants must agree to use adequate contraception (i.e., barrier method of birth control; vasectomized partner; abstinence; ovarian suppression if indicated for breast cancer therapy) during treatment and for at least 3 weeks after last study dose of ribociclib. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Patient with distant metastases of breast cancer beyond regional lymph nodes and/or evidence of breast cancer recurrence prior to study enrollment
• 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 * Known left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) (testing not mandatory) * Known 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
• 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 antibacterial therapy, etc.)
• Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 2 years before enrollment. Note: Patients with adequately treated, basal or squamous cell skin carcinoma or curatively resected cervical cancer in situ are eligible
• 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)
• Patients must not receive any additional anti-cancer therapy or investigational agents or devices during study therapy. Anti-cancer therapies include chemotherapy and endocrine therapy. Patients may have participated in a study involving an investigational drug prior to enrollment, however, at least 30 days must have elapsed prior to enrollment for this protocol, or within 5-half-lives of the investigational drug(s), whichever is longer
• Patient is currently receiving any of the following substances within 7 days before registration: * Concomitant medications, herbal supplements, and/or fruits (e.g., grapefruit, pummelos, 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 * Patients that are taking herbal medications or dietary supplements that are known strong inhibitors or inducers of CYP3A4/5 or patients with known risk of QT prolongation using supplements that include but are not limited to: St. John’s wort, kava, ephedra (ma huang), ginko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, black cohosh and ginseng * Medications with a known risk for QT prolongation and/or TdP (may precipitate QT prolongation and TdP in combination with ribociclib) * Chronic use of oral corticosteroids such as dexamethasone or prednisone. Short term oral steroid use (anticipated duration of 5 days or less) is permitted. Use of topical steroids is permitted