Dendreon Lymph Node Biopsy in Metastatic Castrate-Resistant Prostate Cancer

This is a pilot study of mCRPC patients planning to undergo therapy with sipuleucel-T immunotherapy. Consenting patients will be randomized 3:1 between immediate sipuleucel-T immunotherapy followed by lymph node biopsy (the post-treatment experimental group) or immediate lymph node biopsy followed by sipuleucel-T immunotherapy (the pre-treatment control group). Peripheral blood will be collected before, during, and after treatment with sipuleucel-T and evaluated for evidence of sipuleucel-T induced immune activation. Lymph nodes collected at biopsy will also be evaluated for evidence of sipuleucel-T induced immune activation. Patients will be followed for 3 months for safety and 6 months for disease progression.

Inclusion criteria

• Age ≥ 18 years
• ECOG performance status 0 or 1
• Life expectancy of ≥ 6 months
• 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 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 one of the following:

• 2 consecutive PSA levels that are ≥ 50% above the PSA nadir achieved on ADT and obtained at least 1 week apart
• CT or MRI based evidence of disease progression (soft tissue or nodal) according to PCWG2 criteria or 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 PET/CT)
• Adequate laboratory parameters
• A minimum of 4 weeks from any major surgery prior to registration. Coincident standard of care surgery with the research biopsy is permitted during the study.

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
• 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 registration
• Any condition which, in the opinion of the investigator, would preclude participation in this trial