Clinical Trials Logo

Clinical Trial Summary

This randomized pilot trial studies vaccine therapy and pembrolizumab in treating patients with prostate cancer that does not respond to treatment with hormones (hormone-resistant) and has spread to other places in the body (metastatic). Vaccines made from deoxyribonucleic acid (DNA), such as pTVG-HP plasmid DNA vaccine, may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as pembrolizumab, may find tumor cells and help kill them. Giving pTVG-HP plasmid DNA vaccine and pembrolizumab may kill more tumor cells.


Clinical Trial Description

PRIMARY OBJECTIVES: I. To evaluate the safety of pembrolizumab in combination with pTVG-HP (pTVG-HP plasmid DNA vaccine) in patients with castration-resistant, metastatic prostate cancer. II. To determine the 6-month progression-free survival and median time to radiographic progression in patients with castration-resistant metastatic prostate cancer treated with pembrolizumab in combination with pTVG-HP. III. To evaluate the anti-tumor response rates (objective response rate and prostate specific antigen [PSA] response rate, using Prostate Cancer Clinical Trials Working Group 2 [PCWG2] criteria) in patients with castration-resistant metastatic prostate cancer treated with pembrolizumab in combination with pTVG-HP. SECONDARY OBJECTIVES: I. To determine whether either treatment sequence, or prostatic acid phosphatase (PAP)-specific immune response, is associated with prolonged (6-month) radiographic progression-free survival. II. To evaluate effects of schedule (concurrent versus delayed administration of pembrolizumab) on the magnitude of PAP-specific T-cell responses, programmed death receptor-1 (PD-1) expression on circulating T cells, and ligands for PD-1 (PD-L1) expression on circulating epithelial cells (CEC) and on tumor biopsies. III. To determine the median time to radiographic progression using a concurrent administration schedule TERTIARY OBJECTIVES: I. To evaluate effects of treatment on number of circulating tumor cells. II. To evaluate PAP-specific antibody responses following treatment with pembrolizumab and pTVG-HP DNA vaccine (pTVG-HP plasmid DNA vaccine). III. To determine whether either treatment sequence elicits immunologic antigen spread to other prostate-associated antigens. IV. To determine whether pre-existing or vaccine-induced PD-L1 expression on CEC or tumor biopsies is predictive of objective clinical response. V. To determine whether treatment elicits expression of other regulatory molecules on tumor-specific T cells (e.g. hepatitis A virus cellular receptor 2 [TIM3], B and T lymphocyte associated [BTLA], and lymphocyte-activation gene 3 [LAG3]) or tumor cells (e.g. tumor necrosis factor receptor superfamily, member 14 [HVEM], phosphatidyl serine, ligands for programmed death receptor-2 [PD-2] [PD-L2]). VI. To determine whether PD-1-regulated antigen-specific T cells identified by trans vivo delayed-type hypersensitivity (DTH) testing can identify patients who develop objective clinical responses with PD-1 blockade therapy in combination with pTVG-HP. VII. To determine whether changes in lymph nodes and soft tissue tumor lesions are observed by fluorothymidine F-18 (FLT) positron emission tomography (PET)/computed tomography (CT) after treatment with vaccine with or without pembrolizumab. VIII. To determine if PD-1 inhibitor therapy in combination with pTVG-HP will change number and activity (SUV) in osteoblastic metastases as measured by NaF PET/CT. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive pTVG-HP plasmid DNA vaccine intradermally (ID) every other week on days 1, 15, 29, 43, 57, and 71 and pembrolizumab intravenously (IV) over 30 minutes every 3 weeks on days 1, 22, 43, and 64. ARM II: Patients receive pTVG-HP plasmid DNA vaccine ID as in Arm I and pembrolizumab IV over 30 minutes every 3 weeks on days 85, 106, 127, and 148. After completion of study treatment, patients are followed up 3, 6, 9, and 12 months and then annually for 2 years. ARM III: Extended Treatment. Patients received pTVG-HP + Pembrolizumab Extended Treatment ARM IV: Extended Treatment. Patients receive pTVG-HP every two weeks, and Pembrolizumab every 4 weeks ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02499835
Study type Interventional
Source University of Wisconsin, Madison
Contact
Status Completed
Phase Phase 1/Phase 2
Start date July 1, 2015
Completion date July 27, 2023

See also
  Status Clinical Trial Phase
Active, not recruiting NCT03796767 - Salvage Oligometastasectomy and Radiation Therapy in Recurrent Prostate Cancer Phase 2
Completed NCT04400656 - PROState Pathway Embedded Comparative Trial
Completed NCT05735223 - A Prospective Study to Evaluate the Impact of Maximal Urethral Length Preservation Technique During Robotic Laparoscopic Prostatectomy on the Stretched Flaccid Penile Length and Continence N/A
Recruiting NCT04175431 - Prostate Specific Membrane Antigen (PSMA) or (FACBC) PET/CT Site-Directed Therapy for Treatment of Prostate Cancer, Flu-BLAST-PC Study Phase 2
Completed NCT05197257 - 68Ga-PSMA-11 PET in Patients With Prostate Cancer Phase 3
Withdrawn NCT03982173 - Basket Trial for Combination Therapy With Durvalumab (Anti-PDL1) (MEDI4736) and Tremelimumab (Anti-CTLA4) in Patients With Metastatic Solid Tumors Phase 2
Terminated NCT02491411 - Dexamethasone Prior to Re-treatment With Enzalutamide in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer Previously Treated With Enzalutamide and Docetaxel N/A
Active, not recruiting NCT02254746 - A Phase I-II Dose Escalation Study of Stereotactic Body Radiation Therapy in Patients With Localized Prostate Cancer N/A
Active, not recruiting NCT05496959 - 177-Lutetium-PSMA Before Stereotactic Body Radiotherapy for the Treatment of Oligorecurrent Prostate Cancer, The LUNAR Study Phase 2
Completed NCT02940262 - Gallium Ga 68-labeled PSMA-11 PET/CT in Detecting Recurrent Prostate Cancer in Patients After Initial Therapy Phase 3
Recruiting NCT04391556 - Interest of PET-PSMA Imaging Potentialised by Androgen Blockade in Localized Prostatic Adenocarcinoma Phase 2
Enrolling by invitation NCT03503643 - Hemi-Gland Cryoablation for Prostate Cancer at UCLA
Recruiting NCT05832086 - Intermittent Fasting Using a Fasting-Mimicking Diet to Improve Prostate Cancer Control and Metabolic Outcomes Phase 2
Suspended NCT05064111 - Utility of Adding MR Fusion to Standard US Guided Prostate Biopsy
Not yet recruiting NCT04031378 - Single Dose Radiotherapy (SDRT) With or Without Adjuvant Systemic Therapy for Oligometastatic Prostate Cancer Phase 2
Recruiting NCT02600156 - Focal Laser Ablation of Low to Intermediate Prostate Cancer Tumors N/A
Recruiting NCT05726292 - A Study of Enzalutamide Plus the Glucocorticoid Receptor Antagonist Relacorilant Versus Placebo for Patients With High-risk Localized Prostate Cancer Phase 2
Recruiting NCT04423211 - Treating Prostate Cancer That Has Come Back After Surgery With Apalutamide and Targeted Radiation Based on PET Imaging Phase 3
Terminated NCT03718338 - Mechanisms of Metabolic and Hormone Action on Plaque Formation in Brain and Carotid Vessels in Patients With Prostate Adenocarcinoma
Terminated NCT02564549 - MRI-Based Active Surveillance to Avoid the Risks of Serial Biopsies in Men With Low-Risk Prostate Ca N/A