Evaluation of Lymph Node Metastases in Men Undergoing Treatment With Sipuleucel-T for Metastatic Castrate-resistant Prostate Cancer
Overview
- Phase
- Phase 1
- Intervention
- Sipuleucel-T
- Conditions
- Prostate Cancer
- Sponsor
- Duke University
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- anti-PA2024 immune response in lymph node-derived leukocytes
- Status
- Completed
- Last Updated
- 6 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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:
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
Arms & Interventions
Arm A
Pre-treatment control group will be randomized to immediate lymph node biopsy followed by sipuleucel-T immunotherapy.
Intervention: Sipuleucel-T
Arm A
Pre-treatment control group will be randomized to immediate lymph node biopsy followed by sipuleucel-T immunotherapy.
Intervention: Lymph Node Biopsy
Arm B
Post-treatment experimental group will be randomized to immediate sipuleucel-T immunotherapy followed by lymph node biopsy.
Intervention: Sipuleucel-T
Arm B
Post-treatment experimental group will be randomized to immediate sipuleucel-T immunotherapy followed by lymph node biopsy.
Intervention: Lymph Node Biopsy
Outcomes
Primary Outcomes
anti-PA2024 immune response in lymph node-derived leukocytes
Time Frame: Lymph node biopsy, approximately 10 weeks
Proportion of patients with lymph node-derived leukocytes showing anti-PA2024 activity as measured by IFNγ ELISPOT
anti-PAP immune response in lymph node-derived leukocytes
Time Frame: Lymph node biopsy, approximately 10 weeks
Proportion of patients with lymph node-derived leukocytes showing anti-PAP activity as measured by IFNγ ELISPOT
anti-PAP immune response in PBMCs
Time Frame: 6 months post-treatment
Proportion of patients with PBMC samples showing anti-PAP activity as measured by IFNγ ELISPOT at each time point
anti-PA2024 immune response in PBMCs
Time Frame: 6 months post-treatment
Proportion of patients with PBMC samples showing anti-PA2024 activity as measured by IFNγ ELISPOT at each time point
Secondary Outcomes
- Serum anti-PA2024 antibody level(Baseline, up to 6 months post-treatment)
- serum anti-PAP antibody level(Baseline, up to 6 months post-treatment)