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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02326805
Recruitment Status : Active, not recruiting
First Posted : December 30, 2014
Results First Posted : November 2, 2021
Last Update Posted : November 2, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE December 24, 2014
First Posted Date  ICMJE December 30, 2014
Results First Submitted Date  ICMJE September 9, 2021
Results First Posted Date  ICMJE November 2, 2021
Last Update Posted Date November 2, 2021
Actual Study Start Date  ICMJE June 3, 2015
Actual Primary Completion Date November 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 6, 2021)
  • Change 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 ]
    change (pre to post-intervention) in CD8+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.
  • Change 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 ]
    change (pre to post-intervention) in CD4+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies.
Original Primary Outcome Measures  ICMJE
 (submitted: December 24, 2014)
  • Change 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 ]
    A two-sided two-sample t test will be used to compare the change in CD8+ positive cells in tumor tissue between the treatment and placebo groups. A subgroup analysis will be performed to compare the change in CD8+ positive cells between study groups in specimens collected by targeted biopsy.
  • Change 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 ]
    A two-sided two-sample t test will be used to compare the change in CD4+ positive cells in tumor tissue between the treatment and placebo groups. A subgroup analysis will be performed to compare the change in CD4+ positive cells between study groups in specimens collected by targeted biopsy.
  • Change in PSA [ Time Frame: Baseline to up to 14 days after last dose ]
    Pearson correlation coefficient will be derived to evaluate the correlation between the change in CD8+ and the change in PSA for participants treated with PROSTVAC.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 6, 2021)
  • Change in PD-L1 Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies [ Time Frame: 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.
  • Change in Prostate-specific Antigen (PSA) [ Time Frame: 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.
  • Change in CD8+ Positive Cells in the Benign Portion of the Prostate Biopsies [ Time Frame: 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.
  • Change in CD4+ Positive Cells in the Benign Portion of the Prostate Biopsies [ Time Frame: 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.
  • Change in PD-L1 Positive Cells in the Benign Portion of the Prostate Biopsies [ Time Frame: 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.
  • Tumor Grade Progression [ Time Frame: 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
  • Change in Tumor Extent [ Time Frame: 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.
  • Proportion of Men With no Cancer in the Post-intervention Biopsy Between Participants Treated With Rilimogene-galvacirepvec and Those Treated With Placebo [ Time Frame: 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.
  • Size of Dominant MRI Lesion [ Time Frame: 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.
  • Incidence of Adverse Events Identified Using the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [ Time Frame: 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.
  • Change in Circulating 15-Mer PSA-specific T Cells [ Time Frame: 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.
  • Change in Soluble Antibodies to Tumor-associated Antigens [ Time Frame: 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.
  • Immunologic Effects of Rilimogene-galvacirepvec on the Target Organ Using Multiplex Immunofluorescence [ Time Frame: 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.
  • Change in International Prostate Symptom Score [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 24, 2014)
  • Change in PD-L1 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 ]
    A two-sided two-sample t test at a significance level of 5% will be performed to compare the PROSTVAC 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.
  • Change in CD8+ positive cells in the benign portion of the prostate biopsies [ Time Frame: 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 PROSTVAC and placebo groups.
  • Change in CD4+ positive cells in the benign portion of the prostate biopsies [ Time Frame: 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 PROSTVAC and placebo groups.
  • Change in PD-L1 positive cells in the benign portion of the prostate biopsies [ Time Frame: 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 PROSTVAC and placebo groups.
  • PSA doubling time [ Time Frame: 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 PROSTVAC and placebo groups.
  • Change in tumor grade [ Time Frame: Baseline to up to 30 days after the last dose ]
    Tumor grade will be assessed by Gleason score. A two-sided two-sample t test at a significance level of 5% will be performed to compare the PROSTVAC and placebo groups. A subgroup analysis will be performed to compare the change in tumor grade between study groups in specimens collected by targeted biopsy.
  • Change in tumor extent [ Time Frame: Baseline to up to 30 days after the last dose ]
    Tumor extent will be assessed by the average percent core involvement from all cores. A two-sided two-sample t test at a significance level of 5% will be performed to compare the PROSTVAC and placebo groups. The primary analysis of changes in tumor extent will be based on random biopsies, the magnetic resonance imaging directed biopsies should not be included. A subgroup analysis will be performed to compare the change in tumor extent between study groups in specimens collected by targeted biopsy.
  • Incidence of adverse events identified using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: 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.
  • Change in circulating immune cell subsets [ Time Frame: 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 PROSTVAC and placebo groups. Pearson correlation coefficients will be derived to evaluate the correlation between the change in circulating immune cell subsets and the change in CD8+, CD4+ and PD-L1 positive cells in PROSTVAC treated subjects.
  • Change in circulating 15-Mer PSA-specific T cells [ Time Frame: 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 PROSTVAC and placebo groups.
  • Change in soluble antibodies to tumor-specific antigens [ Time Frame: 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 PROSTVAC and placebo groups.
  • Immunologic effects of PROSTVAC on the target organ using multiplex immunofluorescence [ Time Frame: 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 PROSTVAC and placebo groups.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE PROSTVAC (PSA-TRICOM) in Preventing Disease Progression in Patients With Localized Prostate Cancer Undergoing Active Surveillance
Official Title  ICMJE Phase II Randomized, Placebo-Controlled Trial of PROSTVAC (PSA-TRICOM) in Patients With Clinically Localized Prostate Cancer Undergoing Active Surveillance
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.
Detailed Description

PRIMARY OBJECTIVES:

I. 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.

II. 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:

I. 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.

II. 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.

IV. 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).

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

VIII. 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.

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

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

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

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

XIII. 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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Stage I Prostate Adenocarcinoma AJCC v7
  • Stage II Prostate Adenocarcinoma AJCC v7
Intervention  ICMJE
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Other: Placebo Administration
    Given SC
  • 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
Study Arms  ICMJE
  • Experimental: Arm I (rilimogene-galvacirepvec)
    Patients receive rilimogene-galvacirepvec SC at baseline and on days 14, 28, 56, 84, 112, and 140.
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Biological: Rilimogene Galvacirepvec
  • Placebo Comparator: Arm II (placebo)
    Patients receive placebo SC at baseline and on days 14, 28, 56, 84, 112, and 140.
    Interventions:
    • Other: Laboratory Biomarker Analysis
    • Other: Placebo Administration
Publications * Parsons JK, Pinto PA, Pavlovich CP, Uchio E, Kim HL, Nguyen MN, Gulley JL, Jamieson C, Hsu P, Wojtowicz M, Parnes H, Schlom J, Dahut WL, Madan RA, Donahue RN, Chow HS. A Randomized, Double-blind, Phase II Trial of PSA-TRICOM (PROSTVAC) in Patients with Localized Prostate Cancer: The Immunotherapy to Prevent Progression on Active Surveillance Study. Eur Urol Focus. 2018 Sep;4(5):636-638. doi: 10.1016/j.euf.2018.08.016. Epub 2018 Sep 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 22, 2019)
154
Original Estimated Enrollment  ICMJE
 (submitted: December 24, 2014)
150
Estimated Study Completion Date  ICMJE December 31, 2022
Actual Primary Completion Date November 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02326805
Other Study ID Numbers  ICMJE NCI-2014-02556
NCI-2014-02556 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
AZ027
HHSN2612012000311
N01-CN-2012-00031
1410547210 ( Other Identifier: Banner University Medical Center - Tucson )
UAZ2014-03-01 ( Other Identifier: DCP )
N01CN00031 ( U.S. NIH Grant/Contract )
P30CA023074 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: John K Parsons The University of Arizona Medical Center-University Campus
PRS Account National Cancer Institute (NCI)
Verification Date October 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP