Clinical trial NCT02036918: Dendreon Lymph Node Biopsy in Metastatic Castrate-Resistant Prostate Cancer
Official title: Evaluation of Lymph Node Metastases in Men Undergoing Treatment With Sipuleucel-T for Metastatic Castrate-resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Prostate Cancer
Keywords: castrate resistant prostate cancer
metastatic
sipuleucel-T
lymphadenectomy
Excisional lymph node biopsy
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2014-01-15
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. ECOG performance status 0 or 1
3. Life expectancy of ≥ 6 months
4. Minimally-symptomatic or asymptomatic, castrate-resistant metastatic prostate cancer, as evidenced by all of the following:

   1. Histologically-confirmed diagnosis of adenocarcinoma of the prostate
   2. 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
   3. 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.
   4. Presence of non-visceral metastases on imaging
   5. 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
5. Radiographic evidence of lymphadenopathy, defined as a lymph node greater than 1 cm in diameter on axial imaging (CT or MRI or PET/CT)
6. Adequate laboratory parameters
7. 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:

1. Prior treatment with sipuleucel-T
2. Allergy to any component of sipuleucel-T
3. Inability to undergo leukapheresis
4. History of neuroendocrine variants of prostate cancer, including small cell carcinoma of the prostate
5. Extensive prior surgery/radiation present that would render the biopsy highly complex and the risk of intraoperative injury high
6. Any chronic medical condition requiring daily corticosteroids or other immunosuppressants
7. Solid organ transplantation requiring immunosuppression
8. Visceral (e.g. lung, liver) metastases
9. Known brain metastases
10. History of spinal cord compression
11. Untreated/unstabilized pathologic long bone fractures
12. Other malignancy, except non-melanoma skin cancer, with a ≥ 30% probability of recurrence within 24 months
13. Administration of any investigational therapeutic within 30 days of registration
14. Any condition which, in the opinion of the investigator, would preclude participation in this trial

Primary outcomes:
measure: anti-PA2024 immune response in lymph node-derived leukocytes
timeFrame: Lymph node biopsy, approximately 10 weeks
measure: anti-PAP immune response in lymph node-derived leukocytes
timeFrame: Lymph node biopsy, approximately 10 weeks
measure: anti-PA2024 immune response in PBMCs
timeFrame: Baseline
measure: anti-PAP immune response in PBMCs
timeFrame: Baseline
measure: anti-PA2024 immune response in PBMCs
timeFrame: Prior to sipuleucel-T infusion 2, approximately 6 weeks
measure: anti-PAP immune response in PBMCs
timeFrame: Prior to sipuleucel-T infusion 2, approximately 6 weeks
measure: anti-PA2024 immune response in PBMCs
timeFrame: Prior to sipuleucel-T infusion 3, approximately 8 weeks
measure: anti-PAP immune response in PBMCs
timeFrame: Prior to sipuleucel-T infusion 3, approximately 8 weeks
measure: anti-PA2024 immune response in PBMCs
timeFrame: 2 weeks after the last sipuleucel-T infusion
measure: anti-PAP immune response in PBMCs
timeFrame: 2 weeks after the last sipuleucel-T infusion
measure: anti-PA2024 immune response in PBMCs
timeFrame: 3 months post-treatment
measure: anti-PAP immune response in PBMCs
timeFrame: 3 months post-treatment
measure: anti-PA2024 immune response in PBMCs
timeFrame: 6 months post-treatment
measure: anti-PAP immune response in PBMCs
timeFrame: 6 months post-treatment
Secondary outcomes:
measure: Serum anti-PA2024 antibody level
timeFrame: Baseline, up to 6 months post-treatment
measure: serum anti-PAP antibody level
timeFrame: Baseline, up to 6 months post-treatment
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Brant Inman, MD
role: PRINCIPAL_INVESTIGATOR
References: