Vaccine Plus Booster Shots in Men With Prostate Cancer Undergoing Treatment With Radical Prostatectomy

Phase 2

Completed

Conditions: Prostatic Neoplasms
Prostate Cancer
Neoplasms, Prostate

Interventions: Biological: PROSTVAC-V/TRICOM
Biological: PROSTVAC-F/TRICOM

Registration Number: NCT02153918

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

- Some men with prostate cancer have their prostate glands removed. The cancer can still come back. Researchers want to know if receiving a vaccine before prostate removal surgery can lead to less recurrence.

Objective:

- To see if a vaccine and booster shots given to men with prostate cancer before surgery changes the immune cells in the prostate gland.

Eligibility:

- Men age 18 and older who have prostate cancer that has not spread, and who want to have their prostate glands removed as treatment.

Design:

* Participants will be screened by their regular cancer care. They may have a small piece of prostate removed.

* Participants must practice effective birth control before and during the study treatment and for 1 month after the last vaccine booster.

* Participants will have a medical history, physical exam, and blood and liver tests. They will be asked about how they perform daily activities.

* Participants will have a magnetic resonance imaging (MRI) scan of the prostate. The scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the scanner.

* Participants will be injected with the vaccine, most likely in the leg. They will be injected with the vaccine booster 3 times over several weeks.

* At each booster visit, participants will have a medical history, physical exam, and blood and liver tests.

* Participants will have another MRI. Then they will have surgery to remove their prostate.

* Participants will have 2 follow-up visits during the year after surgery. They will have a medical history, physical exam, and blood test.

Detailed Description: Background

* Adenocarcinoma of the prostate is the most common cancer diagnosis in American males and follows lung cancer as the leading cause of cancer death.

* Vaccine strategies represent a novel therapeutic approach in the treatment for prostate cancer. One potential target for a prostate cancer vaccine is prostatic specific antigen (PSA), due to its restricted expression on prostate cancer and normal prostatic epithelial cells.

* A neoadjuvant approach may be of potential benefit providing prolonged protection via the patient s immune system against future recurrence.

* PROSTVAC is a vaccine that induces strong immune responses, has shown promising evidence of activity in a randomized phase II study (8.5 month improvement in median overall survival) and is currently in phase III clinical testing.

* This vaccine has been tested in locally recurrent prostate cancer with substantial inflammatory infiltrates within the prostate seen following subcutaneous and intraprostatic injection.

Objectives

-The primary objective is to evaluate the post vaccine immunologic cluster of differentiation 4 (CD4) and cluster of differentiation 8 (CD8) cell infiltrate response of a neoadjuvant vaccine strategy in prostatectomy specimens in patients who plan to undergo radical prostatectomy.

Eligibility

* Patients must have biopsy proven prostate cancer and are surgical candidates for radical prostatectomy

* Must be of sufficient good health to be surgical candidates for radical prostatectomy and have elected radical prostatectomy for management of their prostate cancer

* Granulocyte count is greater than or equal to 1,500/mm(3), Platelet is greater than or equal to 50,000/mm(3), hemoglobin (Hgb) is greater than or equal to 8 g/dL, Bilirubin \< 1.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2.5x upper limit of normal (ULN), Creatinine is less than or equal to 1.5 X ULN

* Pre-intervention biopsy tissue must be available either from outside institution or repeat biopsy

Design

* This study will utilize rV-PSA(L155)-TRICOM (PROSTVAC-V) as a priming vaccination followed by monthly boosting with rF-PSA (L155)-TRICOM (PROSTVAC-F) for 3 months.

* Patients will undergo radical prostatectomy after 4 months of treatment with PROSTVAC-V/F.

* The maximum accrual to the trial will be 27 patients.

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 27

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vaccine Plus Booster Shots	PROSTVAC-V/TRICOM	PROSTVAC-V/TRICOM followed by PROSTVAC-F/ TRICOM boost monthly until radical prostatectomy or off therapy PROSTVAC
Vaccine Plus Booster Shots	PROSTVAC-F/TRICOM	PROSTVAC-V/TRICOM followed by PROSTVAC-F/ TRICOM boost monthly until radical prostatectomy or off therapy PROSTVAC

Primary Outcome Measures

Name	Time	Method
Changes From Baseline to After Surgery of Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Infiltrates	Baseline (pre vaccination) and approximately week 10	Immunologic CD4 and CD8 cell infiltrate response of a neoadjuvant prime/boost vaccine strategy in prostatectomy specimens. Prostate biopsy specimens are collected and stained for CD4 and CD8 cells. Quantification is reported as the number of stained cells per micron squared of surface area. Change will be noted by utilizing computer automated staining analysis. Density of cell infiltrate will be calculated and the pre and post vaccine values will be compared to determine response to vaccine.

Secondary Outcome Measures

Name	Time	Method
Intraprostatic Treg Cell Infiltration With Cluster of Differentiation 4 (CD4)+Forkhead Box P3 (FOX-P3) Staining	Baseline (pre vaccination) and post surgery after last dose of vaccine, approximately week 10	Prostate biopsy samples collected at baseline and at surgery after last dose of vaccine will be stained for analysis of immune cell infiltrate. Quantification will be reported as number of stained cells per micron squared of surface area.
Prostatic Specific Antigen (PSA) Changes Secondary to Vaccination	Baseline (pre vaccination) and approximately week 10	A change in PSA secondary to vaccination is defined as an increase or decrease in PSA value beyond the baseline level. PSA levels of 4.0 ng/ml and lower are considered normal.
Magnetic Resonance Imaging (MRI) Changes Secondary to Vaccination	Baseline (pre vaccination) and approximately week 10	MRI of the prostate was performed for changes in imaging characteristics of prostate cancer pre and post vaccination. MRI changes secondary to vaccination is defined as increase or decrease in the size of lesions from baseline (pre-vaccine) measurements.
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)	Date treatment consent signed to date off study, approximately 33 months and 5 days	Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Count of Participants With Change in Peripheral Prostatic Specific Antigen (PSA)-Specific T Cell Responses	Baseline (pre vaccination) and week 10	Change in peripheral prostatic specific antigen (PSA)-specific T cells will be assessed by the enzyme-linked immunospot (ELISPOT) assay. A change of \>250 cluster of differentiation 4 (CD4) or cluster of differentiation 8 (CD8) cells producing cytokine or positive for cluster of differentiation 107a (CD107a) in response to PSA post vaccination relative to baseline will be considered evidence of an immunologic response to the vaccine. The number of subjects developing positive PSA-Specific T cell responses with vaccination will be reported.