Enzalutamide With Ribociclib in Treating Patients With Metastatic Castrate-Resistant, Chemotherapy Naive Prostate Cancer That Retains Retinoblastoma Expression

Prior exposure to abiraterone acetate or other specific cytochrome P450 (CYP)-17 inhibitors; abiraterone acetate given in the castration-sensitive setting is permissible if stopped at least 6 months prior to initial protocol treatment

Prior exposure to enzalutamide, apalutamide, or other investigational AR directed therapy

Prior chemotherapy for castration resistant disease; chemotherapy given in the castration-sensitive setting is permissible if stopped at least 4 weeks prior to treatment start

Prior isotope therapy with strontium-89, samarium or radium-223 within 12 weeks of treatment start

Administration of antifungal agents (itraconazole, fluconazole, etc) within 4 weeks of treatment start or unrecovered adverse events (AEs) due to agents administered more than 4 weeks of treatment start

History of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis or chronic liver disease

Known symptomatic brain metastases

Use of any prohibited concomitant medications: immunotherapy, 5 alpha reductase inhibitors, spironolactone, diethystilbestrol (DES), ketoconazole, newer medications targeting ARs; NOTE: the concurrent use of all other drugs, over-the-counter medications, or alternative therapies must be documented; the principal investigator should be alerted if the patient is taking any agent that interacts with CYP450 system

Treatment-related toxicity from prior therapy \> grade 2

Peripheral neuropathy \>= 2

History of hypersensitivity to ribociclib or compounds of similar chemical or biologic composition to ribociclib including to peanut and soy or other drugs formulated with polysorbate 80; or enzalutamide

Currently taking any herbal, alternative or food supplements (i.e., prostate cancer \[PC\]-Spes, saw palmetto, St John wort, etc.); all herbal, alternative and food supplements must be discontinued prior to treatment start; patients may continue on a daily multi-vitamin, calcium and vitamin D

Planned surgery or radiation therapy during protocol treatment

Hormonal-acting agents (including DES, aldosterone, and spironolactone but not including gonadotropin-releasing hormone \[GnRH\] agonists or antagonists) are forbidden during the trial and must be stopped prior to treatment start; no washout period will be required for any of these agents

Initiation of bisphosphonate/denosumab therapy during protocol treatment; patients on stable doses of bisphosphonates or denosumab which have been started no less than 4 weeks prior to treatment start may continue on this medication; NOTE: initiation of bisphosphonate/denosumab therapy will be allowed for the treatment of osteoporosis or prevention of skeletal-related events (SRE) during protocol treatment

Patient has a concurrent malignancy or malignancy within 3 years of treatment start, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer

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 a known history of human immunodeficiency virus (HIV) infection (testing not mandatory)

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.)

Patient has 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 treatment start

* 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) at screening

* History of any cardiac arrhythmias, eg., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality within 12 months prior to treatment start

* Family history of corrected QT interval (QTc) prolongation or of unexplainable sudden death at \< 50 years of age

* On screening 12 lead electrocardiogram (ECG), 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 Fridericia corrected QT (QTcF) \> 450 msec; congenital long QT syndrome or family history of long QT syndrome

* Systolic blood pressure (SBP) \> 160 mmHg or \< 90 mmHg

* Bradycardia (heart rate \< 50 at rest), by ECG or pulse, at screening

On screening, inability to determine the QTcF interval on the ECG (i.e.: unreadable or not interpretable) or QTcF \> 450 msec (using Fridericia's correction); all as determined by screening ECG (mean of triplicate ECGs)

Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to treatment start:

* Known strong inducers or inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)/cytochrome P450, family 3, subfamily A, polypeptide 4 (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, dietary supplements

Patient is currently receiving or has received systemic corticosteroids within \< 2 weeks prior to treatment start, or who have not fully recovered from side effects of such treatment

\* 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)

Patient is currently receiving warfarin or other coumarin-derived anticoagulant for treatment, prophylaxis or otherwise; therapy with heparin, low molecular weight heparin (LMWH) or fondaparinux is allowed

PatientParticipation in other studies involving investigational drug(s) within 30 days prior to randomization or within 5 half-lives of the investigational product (whichever is longer) or participation in any other type of medical research judged not to be scientifically or medically compatible with this study. If the patient is enrolled or planned to be enrolled in another study that does not involve an investigational drug, the agreement of the Novartis study medical lead is required to establish eligibility

Patient who has received radiotherapy =\< 4 weeks or limited field radiation for palliation =\< 2 weeks prior to treatment start, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom \>= 30% of the bone marrow was irradiated

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 treatment start

* Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases

Patient has had major surgery within 14 days prior to treatment start or has not recovered from major side effects (tumor biopsy is not considered as major surgery)

Patient has not recovered from all toxicities related to prior anticancer therapies to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 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)

Patient with a Child-Pugh score B or C

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 30 days after stopping treatment and should not father a child in this period; a condom is required to be used by vasectomized men in order to prevent delivery of the drug via seminal fluid

What this study is about