Dendreon Lymph Node Biopsy in Metastatic Castrate-Resistant Prostate Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Sipuleucel-T; Procedure: Lymph Node Biopsy

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.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Arm A; Pre-treatment control group will be randomized to immediate lymph node biopsy followed by sipuleucel-T immunotherapy.	Drug: Sipuleucel-T; Other Names: Provenge; Procedure: Lymph Node Biopsy; Other Names: lymph node dissection; lymphadenectomy; excisional lymph node biopsy
EXPERIMENTAL: Arm B; Post-treatment experimental group will be randomized to immediate sipuleucel-T immunotherapy followed by lymph node biopsy.	Drug: Sipuleucel-T; Other Names: Provenge; Procedure: Lymph Node Biopsy; Other Names: lymph node dissection; lymphadenectomy; excisional lymph node biopsy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Brant Inman, MD, Duke University

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (ACTUAL): February 6, 2019
• Study Completion (ACTUAL): February 6, 2019

Study Registration Dates

• First Submitted: January 13, 2014
• First Submitted That Met QC Criteria: January 13, 2014
• First Posted (ESTIMATE): January 15, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 31, 2020
• Last Update Submitted That Met QC Criteria: March 30, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: metastatic; lymphadenectomy; sipuleucel-T; castrate resistant prostate cancer; Excisional lymph node biopsy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: Pro00047231