SHIP (Selinexor in Hormone Insensitive Prostate Cancer)

Inclusion Criteria:

* Histologically proven adenocarcinoma of the prostate with evidence for skeletal metastases on bone scan and/or CT scan.
* Must have received at least one agent known to impact survival (abiraterone, enzalutamide, etc.).
* Eastern Cooperative Oncology Group (ECOG) less than or equal to (≤ 2) or a Karnofsky Performance Status (KPS) ≥ 60%.
* Serum testosterone levels less than (\<) 50 ng/ml.
* Ongoing gonadal androgen deprivation therapy with luteinising hormone-releasing hormone (LHRH) analogues or orchiectomy. Participants, who have not had an orchiectomy, must be maintained on standard dosing of LHRH analogue therapy at appropriate frequency for the duration of the study.
* Progression of disease despite androgen ablation shown by objective, documented evidence of disease progression (excluding prostate-specific antigen \[PSA\]), defined as one or both of the following:

  1. Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  2. Bone disease progression defined by modified Prostate Cancer Clinical Trials Working Group 2 (PCWG2) with two or more new lesions or bone scan
* Discontinuation of all glucocorticoids prescribed to specifically treat prostate cancer (e.g., as a secondary hormonal manipulation) greater than (\>) 4 weeks prior to receiving first dose of study drug. Glucocorticoids prescribed for a chronic non-cancer-related illness (e.g., asthma or chronic obstructive pulmonary disease \[COPD\]) that is well controlled with medical management are permissible to an equivalent of ≤ 10 milligrams (mg) prednisone daily.
* Laboratory requirements:

  1. White blood cell (WBC) count \> 3,000/microliter (μL)
  2. Absolute neutrophil count (ANC) \> 1,500/μL
  3. Hemoglobin ≥8.0 gram per deciliter (g/dL)
  4. Platelet count ≥150,000/μL
  5. Serum albumin ≥3.0 g/dL
  6. Calculated or measured creatinine clearance \> 30 milliliter per minute (mL/min)
* A biopsy documenting prostate cancer in a target lesion (e.g., lymph node, bone lesion, or soft tissue lesion) within 3 months prior to study entry.
* No evidence of chronic or acute disseminated intravascular coagulation or bleeding tendency.
* Participant must be willing and able to comply with protocol requirements. All participants must sign an informed consent indicating that they are aware of the investigational nature of this study.
* Participant must be willing and able to sign an authorization for the release of their protected health information for study purposes.

Exclusion Criteria:

* Histologic variants other than adenocarcinoma in the primary tumor.
* Participants who require or may be expected to require urgent treatment with docetaxel during the study (e.g., participants with visceral metastases).
* Abnormal hepatic function:

  1. Bilirubin \> 2 times the upper limit of normal (2 x ULN) (except participants with Gilbert's syndrome \[hereditary indirect hyperbilirubinemia\] who must not have a total bilirubin of \> 3 x ULN)
  2. Aspartate transaminase (AST) and alanine transaminase (ALT) \> 2.5 x ULN (except participants with known liver involvement of their mCRPC who must not have an AST and ALT \> 5 x ULN)
* Therapy with other hormonal therapy, including any herbal product known to decrease PSA levels (e.g., Saw Palmetto and PC-SPES) within 4 weeks prior to receiving first dose of study drug.
* Therapy with samarium-153, strontium-89, or radium-223 within 8 weeks prior to first dose of study drug.
* Uncontrolled infection or concomitant illness that is not controlled with medical management.
* Prior external beam radiation therapy completed \< 3 weeks or single fraction of palliative radiotherapy within 14 days prior to first dose of study drug.
* Any "currently active" second malignancy, other than non-melanoma skin cancer. Participants are not considered to have a "currently active" malignancy, if they have completed therapy and are considered by their physician to be at least less than 30% risk of relapse over next 3 months.
* Active psychiatric illnesses/social situations that would limit compliance with protocol requirements.
* Active or uncontrolled autoimmune disease that may require corticosteroid therapy during study.
* Severely compromised immunological state, including known human immunodeficiency virus (HIV).
* Known acute or chronic hepatitis B or C.
* Chemotherapy and other investigational therapies (targeted or immunotherapy) will require a 3-week washout period before treatment initiation.
* Initiation of bisphosphonate therapy within 4 weeks prior to first dose of study treatment. Participants receiving ongoing bisphosphonate or denosumab therapy must have been on stable doses for at least 4 weeks prior to receiving first dose of study treatment. Participants on stable doses of bisphosphonates who show subsequent tumor progression may continue on this medication.
* Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

  1. History or presence of serious uncontrolled ventricular arrhythmias or presence of uncontrolled atrial fibrillation.
  2. Clinically significant resting bradycardia (\< 50 beats per minute).
  3. Any of the following within 3 months prior to study entry: myocardial infarction severe/unstable angina, Coronary Artery Bypass Graft, Grade 3 or 4 Congestive Heart Failure, Cerebrovascular Accident, Transient Ischemic Attack, or Pulmonary Embolism.
  4. Uncontrolled hypertension, as defined by a systolic blood pressure \> 160 mm Hg and/or a diastolic blood pressure \> 90 mm Hg with or without anti-hypertensive medication.
  5. Previous pericarditis; clinically significant pleural effusion in the previous 12 months or current ascites requiring 2 or more interventions per month.
  6. Angina at rest.
* Any acute toxicities due to prior chemotherapy and/or radiotherapy that have not resolved to a National Cancer Institute (NCI) common terminology criteria for adverse events (CTCAE), version 4.03 Grade of ≤ 1. Chemotherapy induced alopecia or Grade 2 neuropathy is allowed.
* Any condition or situation, which in the Investigator's opinion, may put the participant at significant risk, confound the study results, or interfere significantly with the participant's participation in the study.
* Men with a female partner of child-bearing potential, (defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months), who as a couple are unable or unwilling to employ two forms of highly effective contraception (e.g., male condom with spermicide, diaphragm with spermicide, intra-uterine device). Two methods of contraception must be used by participants and their partners through the study and for 3 months after the end of study treatment.
* Body mass index (BMI) \< 1.2 m\^2, in order to prevent a participant from receiving a dose of selinexor \> 70 mg/m\^2.