Ribociclib and Aromatase Inhibitor in Treating Older Participants With Hormone Receptor Positive Metastatic Breast Cancer
Condition: Estrogen Receptor and/or Progesterone Receptor Positive; HER2/Neu Negative; Stage IV Breast Cancer AJCC v6 and v7
MeSH terms: Breast Neoplasms
Intervention: Aromatase Inhibitor; Laboratory Biomarker Analysis; Pharmacokinetic Study; Questionnaire Administration; Ribociclib
Intervention description: Aromatase inhibitor per treating investigator's discretion; Correlative studies; Correlative studies; Ancillary studies; Given PO
Intervention MeSH terms: Estrogens; Aromatase Inhibitors
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 70 Years
Healthy volunteers: No

Summary:

      This phase IIA trial studies the side effects of ribociclib and aromatase inhibitor and how
      well they work in treating participants with hormone receptor positive breast cancer that has
      spread to other places in the body. Ribociclib and aromatase inhibitors may stop the growth
      of tumor cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient has signed the informed consent (ICF) prior to any study procedures being
             performed and is able to comply with protocol requirements

          -  Must be able to swallow ribociclib

          -  Age: >= 70 years at time of enrollment >= 70 to < 74 years, >= 75 years

             * NOTE: A minimum of 20 participants must be >= 75 years. The remaining 20
             participants may be >= 70 to < 74 years OR >= 75 years

          -  Subjects must be able to communicate with the investigator and comply with the
             requirements of the study procedures

          -  Patient has a histologically and/or cytologically confirmed diagnosis of
             estrogen-receptor positive and/or progesterone receptor positive breast cancer,
             HER2-negative breast cancer defined as a negative in situ hybridization test or an IHC
             status of 0, 1+ or 2+, and metastatic breast cancer

          -  First or second line endocrine therapy for metastatic disease. One prior line of
             chemotherapy for metastatic disease is allowed

          -  Absolute neutrophil count >= 1.5 x 10^9 /L, at screening

          -  Platelets >= 100 x 10^9 /L, at screening

          -  Hemoglobin >= 9.0 g/dL, at screening

          -  Patient must have the following laboratory values within normal limits or corrected to
             within normal limits with supplement before the first dose of study medication:

               -  Sodium

               -  Potassium

               -  Magnesium

               -  Total calcium (corrected for serum albumin)

               -  Phosphorous

          -  Serum creatinine < 1.5 mg/dL or creatinine clearance >= 50 mL/min, at screening

          -  In the absence of liver metastases, alanine aminotransferase (ALT) and aspartate
             aminotransferase (AST) < 2.5 x upper limit of normal (ULN); if the patient has liver
             metastases, ALT and AST < 5 x ULN, at screening

          -  Total bilirubin < ULN; or total bilirubin =< 3.0 x ULN or direct bilirubin =< 1.5 x
             ULN in patients with well-documented Gilbert's syndrome, at screening

          -  Patient with available standard 12-lead electrocardiogram (ECG) with the following
             parameters at screening (defined as the mean of the triplicate ECGs):

               -  Fridericia's corrected QT (QTcF) interval at screening < 450msec (using
                  Fridericia's correction)

               -  Resting heart rate 50-90 beats per minute (bpm)

        Exclusion Criteria:

          -  Patient received prior treatment with any CDK4/6 inhibitor

          -  Patient has a known hypersensitivity to any of the excipients of ribociclib

          -  Patients with a prior malignancy diagnosed within 2 years AND with evidence of disease
             (except adequately treated, basal or squamous cell carcinoma, non-melanomatous skin
             cancer or curatively resected cervical cancer)

          -  Patient with concurrent malignancy that is not clinically stable AND needs
             tumor-directed therapy

          -  Patients with central nervous system (CNS) involvement unless they meet ALL the
             following criteria:

               -  Untreated brain metastases (e.g., lesions < 1cm) not needing immediate local
                  therapy

               -  Previously treated brain metastases not needing immediate local therapy

                    -  At least 4 weeks from prior therapy completion (including radiation and/or
                       surgery) to starting the study treatment

                    -  Clinically stable CNS tumor at the time of screening and not receiving
                       steroids and/or enzyme-inducing anti-epileptic medications for brain
                       metastases

          -  Clinically significant, uncontrolled heart disease and/or cardiac repolarization
             abnormalities, including any of the following:

               -  History of acute coronary syndromes (including myocardial infarction, unstable
                  angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or
                  symptomatic pericarditis within 6 months prior to screening

               -  Documented cardiomyopathy

               -  Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia),
                  complete left bundle branch block, high-grade AV block (e.g. bifascicular block,
                  Mobitz type II and third-degree AV block).

               -  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 Pointe (TdP) including uncorrected hypokalemia
                       or hypomagnesemia, history of cardiac failure, or history of clinically
                       significant/symptomatic bradycardia

                    -  Concomitant use of medication(s) with a known risk to prolong the QT
                       interval and/or known to cause Torsades de Pointe that cannot be
                       discontinued (within 5 half-lives or 7 days prior to starting study drug) or
                       replaced by safe alternative medication

                    -  Inability to determine the QT interval on screening (QTcF, using
                       Fridericia's correction)

               -  Systolic blood pressure (SBP) > 160 mmHg or < 90 mmHg at screening

          -  Patient is currently receiving any of the following medications and cannot be
             discontinued 7 days prior to starting study drug:

               -  Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit
                  hybrids, pummelos, star-fruit, and Seville oranges

               -  That have a narrow therapeutic window and are predominantly metabolized through
                  CYP3A4/5

               -  Herbal preparations/medications, dietary supplements

               -  Warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis or
                  otherwise. Therapy with heparin, low molecular weight heparin (LMWH), newer
                  anticoagulation agents such as direct factor Xa inhibitors, or fondaparinux is
                  allowed

          -  Patient is currently receiving or has received systemic corticosteroids =< 2 weeks
             prior to starting study drug, or who have not fully recovered from side effects of
             such treatment

             * The following uses of corticosteroids are permitted: single doses, topical
             applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways
             diseases), eye drops or local injections (e.g., intra-articular)

          -  Patient has impairment of gastrointestinal (GI) function or GI disease that may
             significantly alter the absorption of the study drugs (e.g., ulcerative diseases,
             uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel
             resection)

          -  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 study or compromise compliance with the protocol
             (e.g. chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled
             fungal, bacterial or viral infections, etc.)

          -  Participation in a prior investigational study within 30 days prior to enrollment or
             within 5 half-lives of the investigational product, whichever is longer

          -  Patient has had major surgery and/or radiotherapy within 14 days prior to starting
             study drug or has not recovered from major side effects (tumor biopsy is not
             considered as major surgery)

          -  Patient with a Child-Pugh score B or C

          -  Patient has not recovered from the acute effects of prior systemic therapy (until the
             toxicity resolves to either baseline or at least grade 1) except for residual alopecia
             or peripheral neuropathy

          -  Patient has a history of non-compliance to medical regimen or inability to grant
             consent

          -  Sexually active males unless they use a condom during intercourse while taking the
             drug and for 21 days after stopping treatment and should not father a child in this
             period; a condom is required to be used also by vasectomized men in order to prevent
             delivery of the drug via seminal fluid