Phase IB Trial of Radium-223 and Niraparib in Patients With Castrate Resistant Prostate Cancer (NiraRad)

Inclusion Criteria:

* Histologic or cytologic diagnosis of adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features
* Bone metastases
* Documented progressive metastatic CRPC based on at least one of the following criteria:

  * PSA progression defined as a miminum of 2 rising PSA levels with a minimum of a 1 week interval and a minimum PSA of 2 ng/mL

    -1.0 ng/mL is the minimal starting PSA value if confirmed rise is the only indication of progression
  * Soft-tissue progression defined as an increase \>= 20% in the sum of the longest diameter (LD) of all target lesions based on the smallest sum LD since treatment started or the appearance of one or more new lesions or the appearance of new lesions
  * Documented appearance of new lesions by bone scan
* Agree to undergo a tumor/bone marrow biopsy or submit archival tissue. Note: Tissue sample collected from primary or metastatic site is acceptable on study. Once each stratum begins enrollment at the 300mg dose level, 5 subjects from each stratum will complete a bone marrow biopsy. Due to the dose assignment method used in this study, the 10 subjects requiring a bone marrow biopsy on study will be determined on a case by case basis after consent
* Age ≥ 18 years.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
* Must have received at least 1 line of AR-targeted therapy or androgen bio-synthesis inhibitor (e.g., abiraterone acetate, enzalutamide, apalutamide) for prostate cancer
* Testosterone =\< 50 ng/dL; subjects must continue primary androgen deprivation with an luteinizing hormone-releasing hormone (LHRH) analogue (agonist or antagonist) if they have not undergone orchiectomy
* Subjects on long term (\>= 6 months) first generation anti-androgen therapy (e.g. flutamide, bicalutamide, nilutamide) will need to discontinue anti-androgen therapy for 4 weeks (wash out period) and show evidence of disease progression off the anti-androgen; subjects that have been on a first generation anti-androgen 6 months or less will need to discontinue therapy prior to registration (no wash out period required)
* Subjects on second generation anti-androgen therapy (enzalutamide) or androgen bio-synthesis inhibitor (abiraterone acetate) will need to discontinue therapy 2 weeks prior to registration (wash out period)
* Subjects on treatment with chemotherapy or any investigational therapeutic agent will need to discontinue therapy 4 weeks prior to registration (wash out period)
* Absolute neutrophil count (ANC) \>= 1,500/uL
* Hemoglobin \>= 10 g/dL
* Platelet count \>= 150,000/uL
* Creatinine =\< 1.5 x the institutional ULN
* Potassium \> 3.5 mmol/L (within institutional normal range)
* Total Bilirubin =\< 1.5 ULN (unless documented Gilbert's disease)
* Serum glutamic oxaloacetic transaminase (SGOT) aspartate aminotransferase (AST) =\< 2.5 x ULN
* Serum glutamate pyruvate transaminase (SGPT) alanine aminotransferase (ALT) =\< 2.5 x ULN
* Men must agree to use adequate contraception prior to study entry, for the duration of study participation and for at least 6 months after last radium 223 dose
* Must be able to take oral medication without crushing, dissolving or chewing capsules
* May have received prior radiation therapy or surgery; however, at least 21 days must have elapsed since completion of radiation therapy or surgery and patient must have recovered from all side effects at the time of registration
* Ability to understand and the willingness to sign a written informed consent document that is approved by the local institutional review board

Exclusion Criteria:

* Concurrent treatment with any other investigational therapeutic agents
* More than one prior line of chemotherapy
* More than one prior line of therapy with a second generation anti-androgen (enzalutamide, ARN-509, etc.) or androgen bio-synthesis inhibitor (abiraterone acetate, TAK 700, etc.); patient may have had one second generation anti-androgen or androgen bio-synthesis inhibitor but not both sequentially; subjects that have received combination therapy with second generation anti-androgen plus an androgen bio-synthesis inhibitor would be eligible (e.g., enzalutamide plus abiraterone acetate as one line of therapy on a clinical trial). Note, subjects who have had one line of therapy in a hormone-sensitive setting or one line of therapy in castrate resistant setting are eligible for study.
* Prior isotope therapy with strontium-89, samarium or RAD223
* Subjects with known symptomatic brain metastases
* 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
* Pre-planned concurrent cytotoxic chemotherapy, surgery, or radiation therapy during protocol treatment; radiation therapy is not permitted while on study
* All hormonal-acting agents (including diethylstilbestrol/DES, aldosterone, and spironolactone) must be discontinued before registration; no washout period will be required for any of these agents
* Initiation of bisphosphonate/denosumab therapy during the study; subjects on stable doses of bisphosphonates or the tumor necrosis factor receptor superfamily member 11a, subfamily L (RANK-L) inhibitor, denosumab, which have been started no less than 4 weeks prior to registration, may continue on this medication
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association class III and IV heart failure), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements or concurrent medications that alter cardiac conduction
* Subjects with a "currently active" second malignancy other than non-melanoma skin or superficial urothelial cancers are not eligible; Subjects are not considered to have a "currently active" malignancy if they have completed therapy and are now considered without evidence of disease for 2 years
* Subjects with any known history of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML)
* Subjects with known persistent (\> 4 weeks) \>= grade 2 toxicity from prior cancer therapy
* Subjects with known \>= grade 3 hematological toxicity lasting greater than 7 days with the last chemotherapy regimen
* Subjects with chronic conditions associated with non-malignant abnormal bone growth (e.g., Paget's disease of bone)
* Subjects who have used any of the following within 4 weeks prior to registration: blood or platelet transfusions, erythropoietin, and biologic response modifiers such as granulocyte macrophage colony-stimulating factor (GM-CSF) or granulocyte colony-stimulating factor (G-CSF)
* Subjects with baseline QT prolongation \> 470 msec
* Subjects receiving concomitant medications that prolong corrected QT interval (QTc)
* Subjects with bulky visceral disease defined as \> 4 cm
* Known disorder affecting gastrointestinal absorption
* Subjects with known allergies, hypersensitivity, or intolerance to niraparib or its excipients
* Subjects requiring escalating doses of prednisone or steroids for control of disease at the time of screening. Note: If subjects are receiving prednisone or steroids, they must continue on the same dose they were receiving at the time of screening while being treated on study
* HIV positive subjects with 1 or more of the following:

  * Not receiving highly active antiretroviral therapy
  * A change in antiretroviral therapy within 6 months of the start of screening (except if, after consultation with the sponsor on exclusion criterion 26c. a change is made to avoid a potential drug-drug interaction with the study drug)
  * receiving antiretroviral therapy that may interfere with the study drug (consult the sponsor for review of medication prior to enrollment)
  * CD4 cont \<350 at screening
  * An acquired autoimmunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening