Ignite Creation Date:
2024-05-06 @ 7:14 AM
Last Modification Date:
2024-10-26 @ 11:46 AM
Study NCT ID:
NCT02499835
Status:
COMPLETED
Last Update Posted:
2023-08-01
First Post:
2015-07-14
Brief Title:
Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant Metastatic Prostate Cancer
Sponsor:
University of Wisconsin Madison
Organization:
University of Wisconsin Madison
Study Overview
Official Title:
Pilot Trial of pTVG-HP DNA Vaccine and Pembrolizumab in Patients With Castration-Resistant Metastatic Prostate Cancer
Status:
COMPLETED
Status Verified Date:
2023-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
Detailed 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 eg hepatitis A virus cellular receptor 2 TIM3 B and T lymphocyte associated BTLA and lymphocyte-activation gene 3 LAG3 or tumor cells eg 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 PETcomputed 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 PETCT
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
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 eg hepatitis A virus cellular receptor 2 TIM3 B and T lymphocyte associated BTLA and lymphocyte-activation gene 3 LAG3 or tumor cells eg 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 PETcomputed 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 PETCT
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| Protocol Version 3192018 | OTHER | UW Madison | None |
| 2015-0453 | OTHER | None | None |
| NCI-2015-01154 | REGISTRY | None | None |
| A534260 | OTHER | None | None |
| SMPHMEDICINEHEM-ONC | OTHER | None | None |