Dendreon Lymph Node Biopsy in Metastatic Castrate-Resistant Prostate Cancer

Study Overview
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Brief Summary
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This study aims to evaluate patients with metastatic castrate-resistant prostate cancer (mCRPC) undergoing treatment with sipuleucel-T for evidence of treatment-associated immune activation in lymph nodes and peripheral blood.

Detailed Description
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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.

Official Title
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Evaluation of Lymph Node Metastases in Men Undergoing Treatment With Sipuleucel-T for Metastatic Castrate-resistant Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Sipuleucel-T
* Procedure: Lymph Node Biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Pre-treatment control group will be randomized to immediate lymph node biopsy followed by sipuleucel-T immunotherapy. | Drug: Sipuleucel-T<br> <br> * Other names: Provenge;Procedure: Lymph Node Biopsy<br> <br> * Other names: excisional lymph node biopsy;|
| Experimental: Arm B<br>Post-treatment experimental group will be randomized to immediate sipuleucel-T immunotherapy followed by lymph node biopsy. | Drug: Sipuleucel-T<br> <br> * Other names: Provenge;Procedure: Lymph Node Biopsy<br> <br> * Other names: excisional lymph node biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| anti-PA2024 immune response in lymph node-derived leukocytes | Proportion of patients with lymph node-derived leukocytes showing anti-PA2024 activity as measured by IFNγ ELISPOT | Lymph node biopsy, approximately 10 weeks | 
| anti-PAP immune response in lymph node-derived leukocytes | Proportion of patients with lymph node-derived leukocytes showing anti-PAP activity as measured by IFNγ ELISPOT | Lymph node biopsy, approximately 10 weeks | 
| anti-PA2024 immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PA2024 activity as measured by IFNγ ELISPOT at each time point | Baseline | 
| anti-PAP immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PAP activity as measured by IFNγ ELISPOT at each time point | Baseline | 
| anti-PA2024 immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PA2024 activity as measured by IFNγ ELISPOT at each time point | Prior to sipuleucel-T infusion 2, approximately 6 weeks | 
| anti-PAP immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PAP activity as measured by IFNγ ELISPOT at each time point | Prior to sipuleucel-T infusion 2, approximately 6 weeks | 
| anti-PA2024 immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PA2024 activity as measured by IFNγ ELISPOT at each time point | Prior to sipuleucel-T infusion 3, approximately 8 weeks | 
| anti-PAP immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PAP activity as measured by IFNγ ELISPOT at each time point | Prior to sipuleucel-T infusion 3, approximately 8 weeks | 
| anti-PA2024 immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PA2024 activity as measured by IFNγ ELISPOT at each time point | 2 weeks after the last sipuleucel-T infusion | 
| anti-PAP immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PAP activity as measured by IFNγ ELISPOT at each time point | 2 weeks after the last sipuleucel-T infusion | 
| anti-PA2024 immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PA2024 activity as measured by IFNγ ELISPOT at each time point | 3 months post-treatment | 
| anti-PAP immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PAP activity as measured by IFNγ ELISPOT at each time point | 3 months post-treatment | 
| anti-PA2024 immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PA2024 activity as measured by IFNγ ELISPOT at each time point | 6 months post-treatment | 
| anti-PAP immune response in PBMCs | Proportion of patients with PBMC samples showing anti-PAP activity as measured by IFNγ ELISPOT at each time point | 6 months post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum anti-PA2024 antibody level | Describe any relationship between the magnitude of sipuleucel-T induced leukocyte activation observed in tumor-bearing lymph nodes with systemic (i.e. peripheral blood) studies of sipuleucel-T-induced immune activation | Baseline, up to 6 months post-treatment | 
| serum anti-PAP antibody level | Describe any relationship between the magnitude of sipuleucel-T induced leukocyte activation observed in tumor-bearing lymph nodes with systemic (i.e. peripheral blood) studies of sipuleucel-T-induced immune activation | Baseline, up to 6 months post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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castrate resistant prostate cancer, metastatic, sipuleucel-T, lymphadenectomy, Excisional lymph node biopsy