LEE011 (Ribociclib) in Combination With Docetaxel Plus Prednisone in mCRPC

Inclusion Criteria: * Histologically confirmed prostate cancer. Small cell/neuroendocrine differentiated allowed but not required for study participation. * Progressive metastatic prostate cancer (as defined below in Item #5) despite castrate levels of testosterone (\< 50 ng/dL). * Patients may have either non-measurable disease OR measurable disease * Progressive disease during (or within 4 weeks of completion) with abiraterone, enzalutamide, and/or ARN-509 based on any one of the following: 1. For patients with measurable disease, progression by the RECIST criteria. 2. PSA evidence for progressive prostate cancer consists of a PSA level of at least 2 ng/ml which has risen on at least 2 successive occasions, at least one week apart. If the confirmatory PSA (#3) value is less (i.e., #3b) than the screening PSA (#2) value, then an additional test for rising PSA (#4) will be required to document progression for the purposes of eligibility. 3. Radionuclide bone scan: At least two new foci consistent with metastatic lesions * Testosterone \< 50 ng/dL. Patients must continue primary androgen deprivation with a luteinizing hormone-releasing hormone (LHRH) analogue if they have not undergone orchiectomy. * Patients treated with first generation anti-androgen as most recent systemic therapy (bicalutamide, nilutamide) must have at least 4 weeks elapsed from treatment discontinuation to start of protocol therapy with evidence of disease progression by Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria following discontinuation of prior anti-androgen. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1. * Patient has adequate bone marrow and organ function as defined by the following laboratory values: * Absolute neutrophil count ≥ 1.5 × 109/L. * Platelets ≥ 100 × 109/L. * Hemoglobin ≥ 9 g/dl. * Potassium, total calcium (corrected for serum albumin) and magnesium within normal limits for the institution or corrected to within normal limits before first dose of study medication. * International normalized ratio (INR) ≤ 1.5 unless on direct thrombin inhibitor at time of study entry. * Serum creatinine ≤ 1.5mg/dL or estimated creatinine clearance ≥ 50 ml/min * 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 * 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. * No other systemic therapies for prostate cancer within 28 days or 5 half-lives, whichever is shorter, prior to day 1 of study therapy. * Sexually active males must use a condom during intercourse while taking the drug and for 30 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. Fertile males must use a condom with spermicide (double barrier method). * Age ≥ 18 years * Written informed consent must be obtained prior to any screening procedures and according to local guidelines. Exclusion Criteria: * Patient has a known hypersensitivity to ribociclib or any of its excipients, or prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitor. * Prior chemotherapy for metastatic castration-resistant prostate cancer. Chemotherapy administered in the castration-sensitive setting is allowed provided last dose of chemotherapy was greater than 6 months prior to study entry * Patient has a concurrent malignancy or malignancy within 3 years of randomization, with the exception of adequately treated, basal cell skin cancer, squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer. * Patients with central nervous system (CNS) involvement unless they meet all of the following criteria: * 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. * Baseline screening for CNS metastases is not required unless presence of signs and/or symptoms of involvement * Patient is not able to swallow oral medication and/or 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 significant small bowel resection). * Clinically significant, uncontrolled heart disease and/or recent events 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 12 months prior to screening * History of documented congestive heart failure (New York Heart Association functional classification III-IV) * Patient has a left ventricular ejection fraction (LVEF) \< 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) obtained during Screening. * History of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months of screening. Patients with rate-controlled atrial fibrillation or flutter are permitted. * Bradycardia (heart rate \< 50 bpm at rest), by ECG or pulse, at screening * Congenital long QT syndrome or family history of long QT syndrome * Any of the following abnormalities on screening 12-lead ECG: * QT interval with Fridericia's correction (QTcF) \> 450 msec * Bradycardia (heart rate \< 50 bpm at rest) * Tachycardia (heart rate \> 100 bpm at rest) * P-R interval \> 220msec, * QRS interval \>109 msec * Documented cardiomyopathy * Systolic blood pressure \>160 mmHg or \<90 mmHg at screening * AST and/or ALT \> 1.5 x ULN with concomitant alkaline phosphatase \> 2.5 x ULN * Patient receiving any of the following medications within 7 days of day 1 of study treatment. * 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. * That have a known risk to prolong the QT interval or induce Torsades de Pointes. * Herbal preparations/medications * Patient is currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting study drug at a dose greater than the equivalent of 10 mg prednisone/day, or who have not fully recovered from the side effects of such treatment * The following uses of corticosteroids are permitted: 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). * Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, direct thrombin inhibitors, low molecular weight heparin (LMWH) or fondaparinux is allowed. * Participation in a prior investigational study within 30 days prior to enrollment or within 5 half-lives of the investigational product, whichever is longer * Major surgery 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 who has received radiotherapy ≤4 weeks or limited field radiation for palliation ≤2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia), and/or in whom ≥25% of the bone marrow was irradiated. * Patient has a known history of HIV infection (testing not required) * Patient has not recovered from all toxicities related to prior anticancer therapies to NCI-CTCAE version 4.03 to less than or equal to Grade 1 (Exception to this criterion: patients with grade 1 taxane-induced neuropathy, any grade of alopecia, amenorrhea or other toxicities not considered a safety risk for the patient as per investigator's discretion, are allowed to enter the study). * Patients with chronic liver disease with a Child-Pugh score B or C. * Patients with serious intercurrent infections, or nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this therapy. * Patients with severe psychiatric illness/social situations that would limit compliance with study requirements in the judgment of study investigator. * History of bleeding diathesis. Patients receiving anti-coagulation must be able safely interrupt treatment for tumor biopsy (Phase 2 only) * Patient has a history of non-compliance to medical regimen or inability to grant consent