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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT02326805
First received: December 24, 2014
Last updated: July 11, 2016
Last verified: July 2016
  Purpose
This randomized phase II trial studies how well PROSTVAC (prostate-specific antigen [PSA]-TRICOM) works 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 Intervention Phase
Stage I Prostate Adenocarcinoma
Stage II Prostate Adenocarcinoma
Other: Laboratory Biomarker Analysis
Other: Placebo
Biological: Rilimogene Galvacirepvec
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 CD8+ positive cells in the benign portion of the prostate biopsies [ Time Frame: Baseline to up to 14 days after the last dose ] [ Designated as safety issue: No ]
    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 circulating 15-Mer PSA-specific T cells [ Time Frame: Baseline to up to 14 days after the last dose ] [ Designated as safety issue: No ]
    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 International Prostate Symptom score [ Time Frame: Baseline to up to 6 months post-intervention ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 stroma adjacent to tumor and within the malignant portion of the prostate biopsies [ Time Frame: Baseline to 6 months post-intervention ] [ Designated as safety issue: No ]
    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 PSA [ Time Frame: Baseline to 6 months post-intervention ] [ Designated as safety issue: No ]
    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 in soluble antibodies to tumor-associated antigens [ Time Frame: Baseline to up to 14 days after the last dose ] [ Designated as safety issue: No ]
    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 extent [ Time Frame: Baseline to up to 30 days after the last dose ] [ Designated as safety issue: No ]
    A two-sided two-sample t test at a significance level of 5% will be performed to compare the PROSTVAC 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.

  • Immunologic effects of PROSTVAC on the target organ using multiplex immunofluorescence [ Time Frame: Up to 14 days after the last dose ] [ Designated as safety issue: No ]
    A two-sided two-sample t test at a significance level of 5% will be performed to compare the PROSTVAC and placebo 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 ] [ Designated as safety issue: Yes ]
    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.

  • Size of dominant MRI lesion [ Time Frame: Up to 6 months post-intervention ] [ Designated as safety issue: No ]
    A two-sided two-sample t test at a significance level of 5% will be performed to compare the PROSTVAC 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.

  • Tumor grade progression [ Time Frame: Baseline to up to 30 days after the last dose ] [ Designated as safety issue: No ]
    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. 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 MRI-targeted biopsies were obtained pre- and post-intervention


Estimated Enrollment: 150
Study Start Date: June 2015
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Given SC
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the effect of PROSTVAC (rilimogene-galvacirepvec) on the change (from pre to post-intervention) in cluster of differentiation (CD)8+ 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 programmed cell death ligand 1 (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 assess the effect of PROSTVAC on the size of the dominant magnetic resonance imaging (MRI) lesion in the subgroup of patients with MRIs pre and post-intervention. VIII. To assess the effect of PROSTVAC on circulating 15-Mer PSA-specific, MUC-1 and Brachyury-specific T cells.

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

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

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

XII. 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.

  Eligibility

Ages Eligible for Study:   Child, Adult, Senior
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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, rheumatoid arthritis, Addison's disease, Hashimoto's thyroiditis, or Graves' disease; persons with vitiligo are not excluded; diabetics are not excluded if the condition is well controlled
  • 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
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02326805

Locations
United States, California
USC / Norris Comprehensive Cancer Center Not yet recruiting
Los Angeles, California, United States, 90033
Contact: Mike M. Nguyen    323-865-3041    Mike.Nguyen@med.usc.edu   
Principal Investigator: Mike M. Nguyen         
Cedars-Sinai Medical Center Not yet recruiting
Los Angeles, California, United States, 90048
Contact: Hyung L. Kim    310-423-4700    kimhl@csmc.edu   
Principal Investigator: Hyung L. Kim         
UC Irvine Health/Chao Family Comprehensive Cancer Center Recruiting
Orange, California, United States, 92868
Contact: Edward M. Uchio    714-456-6717    euchio@uci.edu   
Principal Investigator: Edward M. Uchio         
University of California San Diego Recruiting
San Diego, California, United States, 92103
Contact: John K. Parsons    858-822-7874    K0parsons@mail.ucsd.edu   
Principal Investigator: John K. Parsons         
United States, Maryland
Johns Hopkins Bayview Medical Center Recruiting
Baltimore, Maryland, United States, 21224
Contact: Christian P. Pavlovich    410-550-0013    cpavlov2@jhmi.edu   
Principal Investigator: Christian P. Pavlovich         
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: Peter A. Pinto    301-496-6353    pintop@mail.nih.gov   
Principal Investigator: Peter A. Pinto         
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: John Parsons The University of Arizona Medical Center-University Campus
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02326805     History of Changes
Other Study ID Numbers: NCI-2014-02556  NCI-2014-02556  AZ027  N01-CN-2012-00031  HHSN2612012000311  1410547210  UAZ2014-03-01  N01CN00031  P30CA023074 
Study First Received: December 24, 2014
Last Updated: July 11, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Prostatic Neoplasms
Adenocarcinoma
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Vaccines
Metronidazole
Immunologic Factors
Physiological Effects of Drugs
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents

ClinicalTrials.gov processed this record on September 30, 2016