PROSTVAC (PSA-TRICOM) in Preventing Disease Progression in Patients With Localized Prostate Cancer Undergoing Active Surveillance

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02326805
• Collaborator: (none)
• Enrollment: 154
• Locations: 7
• Arms: 2
• Anticipated Duration (Months): 90.9
• Patients Per Site: 22
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well PROSTVAC (prostate-specific antigen [PSA]-TRICOM) works in preventing disease progression in patients with prostate cancer undergoing active surveillance. Vaccines made from a person's tumor cells may help the body build an effective immune response to kill tumor cells that express PSA.

Condition or Disease	Intervention/Treatment	Phase
Stage I Prostate Adenocarcinoma AJCC v7; Stage II Prostate Adenocarcinoma AJCC v7	Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Biological: Rilimogene Galvacirepvec	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the effect of rilimogene-galvacirepvec (PROSTVAC) on the change (from pre to post-intervention) in CD8+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.

2. To determine the effect of PROSTVAC on the change in CD4+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.

SECONDARY OBJECTIVES:

1. To assess the effect of PROSTVAC on PD-L1 positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.

2. To assess the correlation between the change in CD8+ and the change in PSA. III. To assess the effect of PROSTVAC on CD8+, CD4+, and PD-L1 positive cells in the benign portion of the prostate biopsies.

3. To assess the effect of PROSTVAC on the change in PSA. V. To assess the effect of PROSTVAC on tumor grade (Gleason score). VI. To assess the effect of PROSTVAC on tumor extent (percent of positive random biopsy cores).

4. To compare the proportion of men on the two study arms with no cancer on post-intervention biopsy.

5. To assess the effect of PROSTVAC on the size of the dominant lesion on magnetic resonance imaging (MRI) (largest histopathologically confirmed lesion) in the subgroup of patients with MRIs pre and postintervention.

6. To assess the effect of PROSTVAC on circulating 15-Mer PSA-specific, MUC-1 and Brachyury-specific T cells.

7. To assess the effect of PROSTVAC on soluble antibodies to tumor-associated antigens.

8. To assess the immunologic effects of PROSTVAC in prostate tissue using multiplex immunofluorescence.

9. To assess the safety and feasibility of PROSTVAC in the active surveillance population.

10. To assess the effect of PROSTVAC on lower urinary tract symptoms (LUTS) in the active surveillance population.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive rilimogene-galvacirepvec subcutaneously (SC) at baseline and on days 14, 28, 56, 84, 112, and 140.

ARM II: Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140.

After completion of study treatment, patients are followed up for 30 days and then at 6 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 154 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Phase II Randomized, Placebo-Controlled Trial of PROSTVAC (PSA-TRICOM) in Patients With Clinically Localized Prostate Cancer Undergoing Active Surveillance
• Actual Study Start Date: Jun 3, 2015
• Actual Primary Completion Date: Nov 30, 2018
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (rilimogene-galvacirepvec) Patients receive rilimogene-galvacirepvec SC at baseline and on days 14, 28, 56, 84, 112, and 140.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Rilimogene Galvacirepvec; Given SC; Other Names: PROSTVAC Prostvac-V Recombinant Vaccinia-PSA(L155)-TRICOM Vaccine Recombinant Vaccinia-PSA(L155)/TRICOM Recombinant Vaccinia-PSA(L155)/TRICOM Vaccine rVaccinia-Prostate-Specific Antigen/TRICOM Vaccine rVaccinia-PSA(L155)-TRICOM Vaccine
Placebo Comparator: Arm II (placebo) Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140.	Other: Laboratory Biomarker Analysis; Correlative studies; Other: Placebo Administration; Given SC

Outcome Measures

Primary Outcome Measures

1. Change in CD8+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies [Baseline to up to 14 days after the last dose]

   change (pre to post-intervention) in CD8+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.

2. Change in CD4+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies [Baseline to up to 14 days after the last dose]

   change (pre to post-intervention) in CD4+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.

Secondary Outcome Measures

1. Change in PD-L1 Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies [Baseline to 6 months post-intervention]

   A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups. A subgroup analysis will be performed to compare the change in PD-L1 positive cells between study groups in specimens collected by targeted biopsy.

2. Change in Prostate-specific Antigen (PSA) [Baseline to 6 months post-intervention]

   Pearson correlation coefficient will be derived to evaluate the correlation between the change in CD8+ and the change in PSA for participants treated with rilimogene-galvacirepvec.

3. Change in CD8+ Positive Cells in the Benign Portion of the Prostate Biopsies [Baseline to up to 14 days after the last dose]

   A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.

4. Change in CD4+ Positive Cells in the Benign Portion of the Prostate Biopsies [Baseline to up to 14 days after the last dose]

   A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.

5. Change in PD-L1 Positive Cells in the Benign Portion of the Prostate Biopsies [Baseline to up to 14 days after the last dose]

   A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.

6. Tumor Grade Progression [Baseline to up to 30 days after the last dose]

   Assessed by Gleason score. A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups. Fisher's exact test will be performed to compare the proportion of patients with no cancer on the post-intervention biopsy and the proportion of men with an increase in Gleason score to >= 4+3 from baseline to post-intervention biopsy between the two groups. Will be evaluated in the subgroup of patients in whom magnetic resonance imaging (MRI)-targeted biopsies were obtained pre- and post-intervention

7. Change in Tumor Extent [Baseline to up to 30 days after the last dose]

   A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups. Fisher's exact test will be performed to compare the change in tumor extent and the proportion of men with an increase in Gleason score to >/= 4+3 between the two groups.

8. Proportion of Men With no Cancer in the Post-intervention Biopsy Between Participants Treated With Rilimogene-galvacirepvec and Those Treated With Placebo [Up to 14 days after the last dose]

   This analysis will utilize all biopsy data, i.e., from random and target biopsy cores. Fisher's exact test will be performed to compare the proportion of patients with no cancer on the post-intervention biopsy and the proportion of men with an increase in Gleason score to >= 4+3 between the two groups.

9. Size of Dominant MRI Lesion [Up to 6 months post-intervention]

   A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups. Fisher's exact test will be performed to compare the size of dominant MRI lesion and the proportion of men with an increase in Gleason score to >/= 4+3 between the two groups.

10. Incidence of Adverse Events Identified Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [Up to 30 days after the last dose]

    Descriptive statistics of the type and frequency of all adverse events will be generated, including 95% confidence intervals. For each type of the adverse events, a Fisher's exact test will be performed to compare the frequency of the adverse event between the two groups.

11. Change in Circulating 15-Mer PSA-specific T Cells [Baseline to up to 14 days after the last dose]

    A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.

12. Change in Soluble Antibodies to Tumor-associated Antigens [Baseline to up to 14 days after the last dose]

    A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.

13. Immunologic Effects of Rilimogene-galvacirepvec on the Target Organ Using Multiplex Immunofluorescence [Up to 14 days after the last dose]

    A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.

14. Change in International Prostate Symptom Score [Baseline to up to 6 months post-intervention]

    A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Biopsy-proven (consisting of >= 10 tissue cores) adenocarcinoma of the prostate with cancer present in at least one biopsy core, either random or targeted, in the most recent biopsy

• All prior biopsies must meet the following: =< 50% of the total number of random biopsy cores positive for cancer

• Gleason score =< (3+4)

• Clinical stage =< T2a by digital rectal exam (DRE)

• Biopsies performed at outside institutions should have Gleason score confirmed at the study site by a genitourinary (GU) pathologist to ensure eligibility

• Pre-intervention biopsy tissue (most proximal to enrollment) with sufficient tumor tissue to cut 5-10 unstained slides confirmed to be available upon request

• Screening serum PSA < 20 ng/mL; for men treated with 5-alpha-reductase inhibitors (e.g., finasteride, dutasteride), PSA needs to be < 10 ng/mL

• Neutrophil count >= 1,200/mm^3 (>= 1.2 k/uL)

• Stable platelet count >= 75,000/mm^3 (>= 75 k/uL)

• Bilirubin =< 1.5 mg/dL (or =< 3.0 mg/dL for patients with Gilbert's syndrome)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x upper limit of normal (ULN)

• Serum creatinine =< 1.5 x ULN

• Karnofsky >= 70%

• Must agree to use medically acceptable barrier and/or chemical method of contraception while on study and for at least one month following the last vaccine injection; should a participant's partner become pregnant or suspect she is pregnant while the participant is participating in this study, the study physician should be informed immediately; in the event a participant's partner becomes pregnant, the study sponsor may request additional information regarding the course of the pregnancy and if the pregnancy is carried to term, the birth of the child (i.e., the outcome of the pregnancy)

• Ability to understand and the willingness to sign a written informed consent document

• No planned prostate biopsies during the intervention until after the post-intervention biopsy

• Men on stable doses of 5-alpha reductase inhibitors are eligible as long as there is no planned dose change while on study

Exclusion Criteria:

• Have had prior treatment for prostate cancer by surgery, irradiation, local ablative (i.e., cryosurgery or high-intensity focused ultrasound), or androgen-deprivation therapy

• Patients who have prostate cancer with distant metastases

• Have undergone treatment of hormone therapy, immunotherapy, chemotherapy and/or radiation for any malignancies within the past 2 years

• Uncontrolled intermittent illnesses or medical conditions which, in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient; such illnesses/conditions may include, but are not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic or unstable cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Positive for human immunodeficiency virus (HIV) or active infections for hepatitis B, and/or hepatitis C, based on medical history

• Prior solid organ or bone marrow transplant

• Immunodeficiency or splenectomy

• Chronic immunosuppressive therapy within 30 days of screening

• Inflammatory eye disease requiring steroid treatment within 28 days of screening

• Chronic administration (defined as daily or every other day for continued use > 14 days) of systemic corticosteroids within 28 days of the first planned dose of PROSTVAC-V/F; use of inhaled steroids, nasal sprays, and topical creams for small body areas is allowed

• History of or active autoimmune disease including but not limited to autoimmune neutropenia, thrombocytopenia, or hemolytic anemia, systemic lupus erythematosus, Sjogren's syndrome, scleroderma, myasthenia gravis, Goodpasture's syndrome; persons with vitiligo are not excluded; Persons with well-controlled autoimmune endocrinopathies, e.g., diabetes mellitus, Graves' disease, Hashimoto's thyroiditis, Addison's disease are not excluded; persons with well-controlled rheumatoid arthritis, psoriatic arthritis and polymyalgia rheumatica are not excluded

• Known allergy to eggs, egg products

• Prior or concurrent eczema or other eczemoid skin disorders or active skin condition (acute, chronic, or exfoliative) that disrupts the epidermis; persons with psoriasis are not excluded except in cases of:

• any active lesion

• any active lesion in the previous 6 months that required treatment, either systemic or topical

• any prior episode, at any time, extensive enough or severe enough as to require systemic treatment

• Previous adverse reactions to smallpox vaccination

• Unable to avoid close contact or household contact with the following high-risk individuals for three weeks after the day 1 vaccination or until the vaccination site heals completely: (a) children =< 3 years of age, (b) pregnant or nursing women, (c) individuals with prior or concurrent extensive eczema or other eczemoid skin disorders, (d) individuals with other acute, chronic, or exfoliative skin condition, or (e) immunocompromised or immunosuppressed persons (by disease or therapy)

• Participants may not be receiving any other investigational agents

• History of allergic reactions attributed to compounds of similar chemical or biologic composition of PROSTVAC

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
2	Cedars Sinai Medical Center	Los Angeles	California	United States	90048
3	Hoag Memorial Hospital	Newport Beach	California	United States	92663
4	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
5	University of California San Diego	San Diego	California	United States	92103
6	Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224
7	NCI - Center for Cancer Research	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: John K Parsons, The University of Arizona Medical Center-University Campus

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Sep 26, 2018

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02326805
• Other Study ID Numbers: NCI-2014-02556; NCI-2014-02556; AZ027; HHSN2612012000311; N01-CN-2012-00031; 1410547210; UAZ2014-03-01; N01CN00031; P30CA023074
• First Posted: Dec 30, 2014
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Additional relevant MeSH terms: Prostatic Neoplasms; Adenocarcinoma; Metronidazole; Vaccines

Study Results

Participant Flow

Arm/Group Title	Arm I (Rilimogene-galvacirepvec)	Arm II (Placebo)
Arm/Group Description	Patients receive rilimogene-galvacirepvec SC at baseline and on days 14, 28, 56, 84, 112, and 140. Laboratory Biomarker Analysis: Correlative studies Rilimogene Galvacirepvec: Given SC	Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given SC
Period Title: Overall Study
STARTED	106	48
COMPLETED	103	47
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Arm I (Rilimogene-galvacirepvec)	Arm II (Placebo)	Total
Arm/Group Description	Patients receive rilimogene-galvacirepvec SC at baseline and on days 14, 28, 56, 84, 112, and 140. Laboratory Biomarker Analysis: Correlative studies Rilimogene Galvacirepvec: Given SC	Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given SC	Total of all reporting groups
Overall Participants	106	48	154
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65 (7)	64 (8)	64 (8)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	106 100%	48 100%	154 100%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 3.8%	1 2.1%	5 3.2%
Not Hispanic or Latino	98 92.5%	45 93.8%	143 92.9%
Unknown or Not Reported	4 3.8%	2 4.2%	6 3.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	3 2.8%	0 0%	3 1.9%
Native Hawaiian or Other Pacific Islander	1 0.9%	0 0%	1 0.6%
Black or African American	7 6.6%	5 10.4%	12 7.8%
White	91 85.8%	43 89.6%	134 87%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	4 3.8%	0 0%	4 2.6%
Region of Enrollment (participants) [Number]
United States	106 100%	48 100%	154 100%

Outcome Measures

1. Primary Outcome

Title	Change in CD8+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies
Description	change (pre to post-intervention) in CD8+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.
Time Frame	Baseline to up to 14 days after the last dose

Outcome Measure Data

Analysis Population Description

Participants with tumor present in tissue sections from both the pre and post-intervention biopsies

Arm/Group Title	Arm I (Rilimogene-galvacirepvec)	Arm II (Placebo)
Arm/Group Description	Patients receive rilimogene-galvacirepvec SC at baseline and on days 14, 28, 56, 84, 112, and 140. Laboratory Biomarker Analysis: Correlative studies Rilimogene Galvacirepvec: Given SC	Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given SC
Measure Participants	72	28
Mean (Standard Deviation) [number of positive cells per mm^2]	12.2 (151.4)	-6.9 (154)

2. Primary Outcome

Title	Change in CD4+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies
Description	change (pre to post-intervention) in CD4+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.
Time Frame	Baseline to up to 14 days after the last dose

Outcome Measure Data

Analysis Population Description

Participants with tumor present on the tissue sections from both the pre and post-intervention biopsies were included in the analysis

Arm/Group Title	Arm I (Rilimogene-galvacirepvec)	Arm II (Placebo)
Arm/Group Description	Patients receive rilimogene-galvacirepvec SC at baseline and on days 14, 28, 56, 84, 112, and 140. Laboratory Biomarker Analysis: Correlative studies Rilimogene Galvacirepvec: Given SC	Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given SC
Measure Participants	69	28
Mean (Standard Deviation) [number of positive cells per mm^2]	4.6 (166.7)	5.8 (261.1)

3. Secondary Outcome

Title	Change in PD-L1 Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies
Description	A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups. A subgroup analysis will be performed to compare the change in PD-L1 positive cells between study groups in specimens collected by targeted biopsy.
Time Frame	Baseline to 6 months post-intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Change in Prostate-specific Antigen (PSA)
Description	Pearson correlation coefficient will be derived to evaluate the correlation between the change in CD8+ and the change in PSA for participants treated with rilimogene-galvacirepvec.
Time Frame	Baseline to 6 months post-intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Change in CD8+ Positive Cells in the Benign Portion of the Prostate Biopsies
Description	A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.
Time Frame	Baseline to up to 14 days after the last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Change in CD4+ Positive Cells in the Benign Portion of the Prostate Biopsies
Description	A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.
Time Frame	Baseline to up to 14 days after the last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Change in PD-L1 Positive Cells in the Benign Portion of the Prostate Biopsies
Description	A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.
Time Frame	Baseline to up to 14 days after the last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Tumor Grade Progression
Description	Assessed by Gleason score. A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups. Fisher's exact test will be performed to compare the proportion of patients with no cancer on the post-intervention biopsy and the proportion of men with an increase in Gleason score to >= 4+3 from baseline to post-intervention biopsy between the two groups. Will be evaluated in the subgroup of patients in whom magnetic resonance imaging (MRI)-targeted biopsies were obtained pre- and post-intervention
Time Frame	Baseline to up to 30 days after the last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	Change in Tumor Extent
Description	A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups. Fisher's exact test will be performed to compare the change in tumor extent and the proportion of men with an increase in Gleason score to >/= 4+3 between the two groups.
Time Frame	Baseline to up to 30 days after the last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	Proportion of Men With no Cancer in the Post-intervention Biopsy Between Participants Treated With Rilimogene-galvacirepvec and Those Treated With Placebo
Description	This analysis will utilize all biopsy data, i.e., from random and target biopsy cores. Fisher's exact test will be performed to compare the proportion of patients with no cancer on the post-intervention biopsy and the proportion of men with an increase in Gleason score to >= 4+3 between the two groups.
Time Frame	Up to 14 days after the last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	Size of Dominant MRI Lesion
Description	A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups. Fisher's exact test will be performed to compare the size of dominant MRI lesion and the proportion of men with an increase in Gleason score to >/= 4+3 between the two groups.
Time Frame	Up to 6 months post-intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	Incidence of Adverse Events Identified Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Description	Descriptive statistics of the type and frequency of all adverse events will be generated, including 95% confidence intervals. For each type of the adverse events, a Fisher's exact test will be performed to compare the frequency of the adverse event between the two groups.
Time Frame	Up to 30 days after the last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Secondary Outcome

Title	Change in Circulating 15-Mer PSA-specific T Cells
Description	A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.
Time Frame	Baseline to up to 14 days after the last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Secondary Outcome

Title	Change in Soluble Antibodies to Tumor-associated Antigens
Description	A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.
Time Frame	Baseline to up to 14 days after the last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Secondary Outcome

Title	Immunologic Effects of Rilimogene-galvacirepvec on the Target Organ Using Multiplex Immunofluorescence
Description	A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.
Time Frame	Up to 14 days after the last dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Secondary Outcome

Title	Change in International Prostate Symptom Score
Description	A two-sided two-sample t test at a significance level of 5% will be performed to compare the rilimogene-galvacirepvec and placebo groups.
Time Frame	Baseline to up to 6 months post-intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	30 days after the last study dose was given
Arm/Group Title	Arm I (Rilimogene-galvacirepvec)		Arm II (Placebo)
Arm/Group Description	Patients receive rilimogene-galvacirepvec SC at baseline and on days 14, 28, 56, 84, 112, and 140. Laboratory Biomarker Analysis: Correlative studies Rilimogene Galvacirepvec: Given SC		Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140. Laboratory Biomarker Analysis: Correlative studies Placebo Administration: Given SC
All Cause Mortality
	Arm I (Rilimogene-galvacirepvec)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/106 (0.9%)		0/48 (0%)
Serious Adverse Events
	Arm I (Rilimogene-galvacirepvec)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/106 (0.9%)		0/48 (0%)
Injury, poisoning and procedural complications
Fall	1/106 (0.9%)		0/48 (0%)
Other (Not Including Serious) Adverse Events
	Arm I (Rilimogene-galvacirepvec)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	103/106 (97.2%)		48/48 (100%)
Gastrointestinal disorders
Diarrhea	10/106 (9.4%)		6/48 (12.5%)
Nausea	9/106 (8.5%)		2/48 (4.2%)
General disorders
Fatigue	43/106 (40.6%)		14/48 (29.2%)
Fever	17/106 (16%)		6/48 (12.5%)
Injection site reaction	95/106 (89.6%)		45/48 (93.8%)
Hepatobiliary disorders
Flu like syndromes	63/106 (59.4%)		30/48 (62.5%)
Infections and infestations
Upper respiratory infection	10/106 (9.4%)		4/48 (8.3%)
Injury, poisoning and procedural complications
Bruising	6/106 (5.7%)		3/48 (6.3%)
Investigations
White blood cell decreased	1/106 (0.9%)		4/48 (8.3%)
Musculoskeletal and connective tissue disorders
Back pain	7/106 (6.6%)		4/48 (8.3%)
Myalgia	8/106 (7.5%)		2/48 (4.2%)
Nervous system disorders
Dizziness	10/106 (9.4%)		0/48 (0%)
Headache	23/106 (21.7%)		9/48 (18.8%)
Renal and urinary disorders
Renal and urinary disorders - others	2/106 (1.9%)		4/48 (8.3%)
Respiratory, thoracic and mediastinal disorders
Sore throat	5/106 (4.7%)		3/48 (6.3%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	2/106 (1.9%)		4/48 (8.3%)
Skin and subcutaneous tissue disorders - other	3/106 (2.8%)		4/48 (8.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.