Selinexor in Treating Patients With Abiraterone Acetate and/or Enzalutamide Refractory Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria

• •Histologically confirmed adenocarcinoma of the prostate
• •Patients must have castrate levels of testosterone (\< 50 ng/dL) on gonadotropin-releasing hormone (GnRH) analogues or have had prior orchiectomy; GnRH analogues must be continued while on study
• •Tumor tissue submitted for molecular and genetic analysis through the companion Stand-up 2 Cancer (SU2C) radiologically guided biopsy of abiraterone and/or enzalutamide refractory mCRPC protocol
• •* Patients who consent to participate in the companion biopsy protocol and are subsequently determined to be ineligible for biopsy are eligible to participate in the current protocol
• •Progressive disease as demonstrated by a rising PSA (at least two determinations) prior to study entry, and/or radiographic evidence of tumor progression in soft tissue according to modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria or identification of new lesions by bone scan (i.e., \>= 2 new lesions)
• •Primary resistance or acquired resistance (i.e., acquired resistance will be defined as disease progression following a period of response defined as \>= 50% decline in PSA within 12 weeks of starting therapy and not otherwise meeting criteria for primary resistance) to any of the following agents/combinations of therapy:
• •Abiraterone acetate; primary resistance to abiraterone will be defined as:
• •* No PSA decline
• •* PSA decline less than 50% after 12 weeks of abiraterone therapy
• •* PSA progression within 12 weeks of abiraterone acetate (AA) treatment (by Prostate Cancer Working Group-2 \[PCWG2\] criteria), after initial response to therapy
• •* Objective progression, by RECIST criteria for soft tissue lesions and by modified PCWG2 criteria for bone lesions within 12 weeks of starting abiraterone treatment
• •* Unequivocal clinical progression (per the treating provider's discretion) within 12 weeks of starting abiraterone treatment
• •Enzalutamide; primary resistance to enzalutamide will be defined as:
• •* No PSA decline
• •* PSA decline less than 50% after 12 weeks of enzalutamide therapy
• •* PSA progression within 12 weeks of enzalutamide treatment (by PCWG2 criteria), after initial response to therapy
• •* Objective progression, by RECIST criteria for soft tissue lesions and by modified PCWG2 criteria for bone lesions within 12 weeks of starting enzalutamide treatment
• •* Unequivocal clinical progression (per the treating provider's discretion) within 12 weeks of starting enzalutamide treatment
• •Other second-generation investigational anti-androgen/androgen-receptor targeted therapies, including apalutamide (ARN-509); primary resistance will be defined as:
• •* No PSA decline
• •* PSA decline less than 50% after 12 weeks of enzalutamide therapy
• •* PSA progression within 12 weeks of enzalutamide treatment (by PCWG2 criteria), after initial response to therapy
• •* Objective progression, by RECIST criteria for soft tissue lesions and by modified PCWG2 criteria for bone lesions within 12 weeks of starting enzalutamide treatment
• •* Unequivocal clinical progression (per the treating provider's discretion) within 12 weeks of starting enzalutamide treatment
• •Combination therapy with abiraterone, enzalutamide and/or other second- generation investigational anti-androgen/androgen-receptor targeted therapies, including ARN-509; primary resistance to combination therapy will be defined as:
• •* No PSA decline
• •* PSA decline less than 50% after 12 weeks of abiraterone and enzalutamide therapy
• •* PSA progression within 12 weeks of abiraterone and enzalutamide treatment (by PCWG2 criteria), after initial response to therapy
• •* Objective progression, by RECIST criteria for soft tissue lesions and by modified PCWG2 criteria for bone lesions within 12 weeks of starting abiraterone and enzalutamide treatment
• •* Unequivocal clinical progression (per the treating provider?s discretion) within 12 weeks of starting abiraterone and enzalutamide treatment
• •Sequenced therapy, including any of the following:
• •* Abiraterone acetate followed by enzalutamide
• •* Primary resistance will be defined per criteria for abiraterone monotherapy primary resistance
• •* Enzalutamide followed by abiraterone acetate
• •* Primary resistance will be defined per criteria for enzalutamide monotherapy primary resistance
• •* Other second-generation investigational anti-androgen/androgen- receptor targeted therapies, including ARN-509
• •* Primary resistance will be defined per criteria for other investigational anti-androgen monotherapy primary resistance
• •Presence of 1 or more bone metastasis
• •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• •Prior and ongoing zoledronic acid or denosumab therapy is allowed
• •Prior therapy with radium-223 is allowed
• •Discontinuation of prior therapy for mCRPC: a washout period of 28 days for the following therapies is required: abiraterone, enzalutamide, fluconazole, itraconazole, flutamide, bicalutamide, nilutamide, and other experimental hormonal agents (ARN509, orteronel \[TAK-700\], etc.), sipuleucel-T (Provenge), other experimental vaccines (PROSTVAC-V/F, etc.), strontium-89, samarium, and radium-223 chloride
• •Leukocytes \> 3,000/mcL
• •Absolute neutrophil count \> 1,500/mcL
• •Platelets \> 125,000/mcL
• •Hemoglobin \>= 5.59 mmol/L or 9 g/dL; up to 5% deviation is tolerated; transfusions and growth factors are allowed
• •Total bilirubin within normal institutional limits
• •Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\]) \< 3 X institutional upper limit of normal
• •Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase \[SGPT\]) \< 3 X institutional upper limit of normal
• •Creatinine within normal institutional limits OR creatinine clearance \> 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• •Ability to understand a written informed consent document, and the willingness to sign it
• •Life expectancy of at least 12 weeks
• •Able to swallow and retain oral medication