History of hypersensitivity to ribociclib or compounds of similar chemical or biologic composition to ribociclib or other drugs formulated with polysorbate ; or enzalutamide; all herbal, alternative and food supplements (i.e., prostate cancer [PC]-Spes, saw palmetto, St John wort, etc.); they must be discontinued prior to treatment start; patients may continue on a daily multi-vitamin, calcium and vitamin D Patients taking vitamin E supplements while on study Patients currently receiving and unable to stop high doses of supplemental vitamin E All herbal, alternative and food supplements (i.e. PC-Spes, saw palmetto, St. John's wort, etc.) must be discontinued before registration; subjects may continue on a daily multi-vitamin, calcium and vitamin D Supplementation with vitamin E greater than % of the daily recommended dose Vitamin D supplementation at > , IU daily Patient must discontinue any and all use of multivitamin and/or vitamin c medication hours before first dose of ascorbic acid Has a serum vitamin D level of ? ng/mL No supplementation with vitamin E is permitted because the selumetinib capsules contain vitamin E Patients taking Vitamin A supplements (>, IU/d) unless discontinued prior to first dose of study drug, or having hypervitaminosis A. Patients may continue on a daily multi-vitamin, calcium and vitamin D, but all other herbal, alternative and food supplements (i.e. prostate cancer [PC]- hope [spes (Latin)], saw palmetto, St Johns wort, etc.) must be discontinued before starting protocol treatment; hormonal-acting agents such as diethylstilbestrol (DES) are forbidden during the trial and must be stopped starting protocol treatment; no washout period will be required; patients on megestrol acetate for hot flashes are allowed to continue therapy Concomitant use of warfarin or other vitamin K antagonists; Note: Subjects receiving antiplatelet agents in conjunction with ibrutinib should be observed closely for any signs of bleeding or bruising, and ibrutinib should be withheld in the event of any bleeding events; supplements such as fish oil and vitamin E preparations should be avoided No supplementation with vitamin E is permitted The ability to take folic acid, vitamin B, and dexamethasone according to protocol The ability to take folic acid, vitamin B, and dexamethasone according to protocol Ability to take folic acid, vitamin B, and dexamethasone according to the protocol instructions Baseline serum vitamin D total -hydroxy level below ng/ml Willing to stop current supplemental vitamin D (multivitamin with vitamin D component is acceptable) Patients taking high-dose vitamin D supplementation (, IU weekly) prior to enrollment Patients with vitamin D total -hydroxy level above ng/ml at baseline testing Patients must have serum -hydroxyvitamin D ([OH]D) drawn at time of enrollment; (NOTE: subjects currently taking vitamin D supplements are eligible for screening) A history of hypersensitivity to selumetinib, or any excipient agents (e.g. Captisol or TPGS- a water soluble form of Vitamin E) Baseline vitamin D level greater than ng/mL Not willing to discontinue use of supplemental vitamin E Patients cannot take any additional vitamin D supplementation during study treatment; patients taking > IU per day prior to treatment will be ineligible or more doses of a vitamin K antagonist before randomization; Able to tolerate daily supplementation of calcium and vitamin D Must have a vitamin D level >= ng/mL after repletion Known hypoparathyroidism, pseudohypoparathyroidism, or vitamin D deficiency, or\n clinical evidence of other conditions known to associated with hypocalcemia,\n including:, hypoalbuminemia, hyperphosphatemia, hypomagnesemia Requires anti-coagulation with warfarin or a vitamin K antagonist Is unable or unwilling to take folic acid or vitamin B supplementation. The use of concomitant antioxidants, such as vitamin C or E, is not allowed Subjects must be off any curcumin, tumeric, or vitamin D supplements for days prior to the initiation of treatment Patients may not have received warfarin or another vitamin K antagonist in the preceding days Concurrent use of any vitamin, herb, or mineral supplements for at least days prior to start of therapy Use of any non-protocol vitamin D supplementation Intolerance of vitamin B, folic acid or dexamethasone Have a history of vitamin B deficiency Patients on vitamin K antagonist warfarin Patients may continue on a daily multi-vitamin, calcium and vitamin D, but all other herbal, alternative and food supplements (i.e. PC-Spes, saw palmetto, St Johns wort, etc.) must be discontinued before registration; patients must not be planning to receive any concurrent cytotoxic chemotherapy, surgery, or radiation therapy during protocol treatment; hormonal-acting agents (including diethylstilbestrol/DES, aldosterone, and spironolactone) are forbidden during the trial and must be stopped prior to registration; no washout period will be required for any of these agents; patients on megestrol acetate for hot flashes are allowed to continue therapy The ability to take folic acid, vitamin B, and dexamethasone according to protocol for all pemetrexed arms Regular use of vitamin D supplements >= , IU per day in the past year; use of supplemental vitamin D or supplements containing vitamin D beyond the protocol-prescribed study treatment is not allowed while enrolled on this clinical trial \r\n* In order to maintain blinding, vitamin D levels should not be routinely checked at screening or during the study by the treating investigator; vitamin D levels will be assayed only as part of the research blood samples collected during the study; if there are concerns related to a participants vitamin D status, the lead principal investigator should be contacted for further discussion Patients who are currently taking vitamin supplements including lycopene and beta-carotene are eligible Inability or unwillingness to take folic acid, vitamin B supplementation or corticosteroids Unable or unwilling to take folic acid or vitamin B Inability or unwillingness to take folic acid or vitamin B or dexamethasone Unwillingness to stop calcium supplementation (during the first cycle of treatment) or vitamin D supplementation throughout the study During time of study period, subjects must agree not to take any new vitamin supplementation or herbal remedy Vitamin K antagonist therapy and an international normalized ratio >. on the day of surgery. Requires anti-coagulation with warfarin or a vitamin K antagonist. No dietary supplements allowed during the study period, except multivitamins, vitamin D and calcium. Supplementation with vitamin E greater than % of the daily recommended dose; any multivitamin containing vitamin E must be stopped prior to initiation of therapy The participant is unwilling or unable to take premedications (folic acid, vitamin B, or corticosteroids) required by the pemetrexed label. Patients taking antioxidant therapy will be excluded from enrollment due to potential interaction with the potential oxidative mechanism of action of Photofrin, including:\r\n* Beta-carotene\r\n* Lutein\r\n* Lycopene\r\n* Selenium\r\n* Vitamin A\r\n* Vitamin C\r\n* Vitamin E Serum vitamin D , hydroxy (OH) < ng/mL Vitamin D insufficiency, defined as (OH)D =< ng/ml Patients with a confirmed history of calcium oxalate nephrolithiasis are excluded; patients with a significant history of malabsorption (e.g. celiac sprue, short bowel syndrome, inflammatory bowel disease [IBD] or other, as determined by the treating physician) are excluded; patients will not be eligible if actively receiving treatment for vitamin D deficiency and have had recent ( month) history of vitamin D supplementation (> IU) Able to obtain and take an acceptable form of vitamin B. Subjects are currently taking vitamin supplementation which includes vitamin B at doses > mg. Current or planned use of cyclosporine, anticoagulants, insulin, oral or injectable vitamin D doses over , IU/day, or tamoxifen Plasma iPTH ? pg/mL if taking < IU vitamin D Subjects receiving ? IU/day vitamin D (ergocalciferol or cholecalciferol) therapy must remain on a stable dose during the study. If taking more than IU/day of vitamin D (ergocalciferol or cholecalciferol), must be willing and able to reduce use to ? IU/day and remain on a stable dose for the duration of the study Serum vitamin D level >= ng/ml Severe vitamin D deficiency with serum -OH vitamin D < ng/ml ( nmol/l) \r\n* Patients with vitamin D levels < ng/ml may be treated with vitamin D and reconsidered for enrollment when levels are sufficient Patients who are currently on stable prescription medications or dietary supplements for CIPN and still symptomatic as defined above will be allowed to participate in the study; related medications are: gabapentin, pregabalin, nortriptyline, amitriptyline, duloxetine, venlafaxine; lidocaine, opioid tramadol and other narcotics; NSAIDs; glutamine, glutathione, vitamin E and vitamin B Patients on vitamin K antagonist (i.e., warfarin) Patients receiving vitamin K antagonist (warfarin) Patients on vitamin K antagonist warfarin Currently consuming IU or more of vitamin D a day Willingness to avoid alternative/additional vitamin D supplementation for the duration of the trial Use of anti-seizure medications phenobarbital or phenytoin, which can disrupt vitamin D metabolism Vitamin D supplementation > , IU/day of vitamin D within days prior to enrollment in step Dietary vitamin A intake >= , IU/day (as determined by dietary supplementation) Participants must be willing to take supplemental oral calcium mg and vitamin D IU daily for six months (which will be supplied by the research study) after receiving denosumab treatment or no treatment Patients on a stable (>= week duration) dose of > IU/day (or equivalent) of vitamin D supplementation Patients may continue on a daily multi-vitamin, calcium and vitamin D, but all other herbal, alternate and food supplements (i.e. PC-Spes, saw palmetto, St John wort, etc.) must be discontinued before treatment start; patients must not be planning to receive any concurrent cytotoxic chemotherapy, surgery for their prostate cancer, or radiation therapy during protocol treatment Vitamin D level ( hydroxy D + hydroxyl D) confirmed by central laboratory review -hydroxy vitamin D ([OH]D) level less than ng/mL prior to study initiation Willingness to avoid alternative/additional vitamin D supplementation for the duration of the trial Use of anti-seizure medications phenobarbital or phenytoin, which can disrupt vitamin D metabolism Vitamin D supplementation > , IU/day of vitamin D within days prior to enrollment Patients taking Vitamin D supplements during the study, unless they have been taking Vitamin D supplements for days or more prior to the start of the study and that the dose of the Vitamin D supplement remain the same throughout the study. Vitamin B, folate or vitamin A deficiency. Rescreening following repletion therapy is acceptable. Regular use of supplemental vitamin D totaling >= , IU/day in the past year\r\n* Use of supplemental vitamin D or supplements containing vitamin D beyond the protocol-prescribed study treatment is not allowed during the treatment period of this clinical trial\r\n* In order to maintain blinding, vitamin D levels should not be routinely checked at screening or during the study by the treating investigator; vitamin D levels will be assayed only as part of the research blood samples collected during the study; if there are concerns related to a participants vitamin D status, the lead principal investigator should be contacted for further discussion