Immune Activation in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Sipuleucel-T Immunotherapy

Inclusion Criteria

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy of >= 6 months (as determined by treating physician)
• Minimally-symptomatic or asymptomatic, castrate-resistant metastatic prostate cancer, as evidenced by all of the following: * Histologically-confirmed diagnosis of adenocarcinoma of the prostate * Evidence of adequate androgen deprivation, as evidence by one of the following: ** Bilateral orchiectomy ** Ongoing luteinizing hormone-releasing hormone (LHRH) agonist (e.g. leuprolide, goserelin) and serum testosterone =< 50 ng/dl ** Ongoing LHRH antagonist (e.g. degarelix) and serum testosterone =< 50 ng/dl * Evidence of prostate cancer resistance to castration, as evidenced by at least one of the following: ** 2 consecutive prostate-specific antigen (PSA) levels that are >= 50% above the PSA nadir achieved on androgen deprivation therapy (ADT) and obtained at least 1 week apart ** Computed tomography (CT) or magnetic resonance imaging (MRI) based evidence of disease progression (soft tissue or nodal) according to Prostate Cancer Working Group 2 (PCWG2) criteria or Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria, or at least 1 new bone scan lesion as compared to the most immediate prior radiologic studies * Presence of non-visceral metastases on imaging * Absence of major symptoms directly attributable to prostate cancer, with the following permissible exceptions: ** Ureteral obstruction secondary to pelvic or retroperitoneal lymphadenopathy ** Bladder outlet obstruction secondary to locally recurrent prostate cancer
• Radiographic evidence of lymphadenopathy, defined as a lymph node greater than 1 cm in diameter on axial imaging (CT or MRI or positron emission tomography [PET]/CT)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
• Platelets >= 100 x 10^9/L
• Hemoglobin (Hb) > 9 g/dL
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase [ALT]/serum glutamate pyruvate (SGPT) =< 2.5 x institutional upper limit of normal (ULN)
• Serum bilirubin =< 1.5 x institutional ULN
• Serum creatinine =< 1.5 x institutional ULN or calculated or measured 24-hour clearance >= 50 mL/min
• A minimum of 4 weeks from any major surgery prior to enrollment; coincident standard of care surgery with the research biopsy is permitted during the study
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Prior treatment with sipuleucel-T
• Allergy to any component of sipuleucel-T
• Inability to undergo leukapheresis
• History of neuroendocrine variants of prostate cancer, including small cell carcinoma of the prostate
• Extensive prior surgery/radiation present that would render the biopsy highly complex and the risk of intraoperative injury high
• Any chronic medical condition requiring daily corticosteroids or other immunosuppressants (e.g. tacrolimus, sirolimus, cyclosporine, azathioprine, mycophenolate mofetil, etc.)
• Solid organ transplantation requiring immunosuppression
• Visceral (e.g. lung, liver) metastases
• Known brain metastases
• History of spinal cord compression
• Untreated/unstabilized pathologic long bone fractures
• Other malignancy, except non-melanoma skin cancer, with a >= 30% probability of recurrence within 24 months
• Administration of any investigational therapeutic within 30 days of enrollment
• Any condition which, in the opinion of the investigator, would preclude participation in this trial