Stage I Prostate Adenocarcinoma AJCC v7, Stage II Prostate Adenocarcinoma AJCC v7
Conditions
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.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERPlacebo Administration
Given SC
BIOLOGICALRilimogene Galvacirepvec
Given SC
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 (from 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 | Baseline to up to 14 days after the last dose | change (from pre to post-intervention) in CD4+ positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in CD8+ Positive Cells in the Benign Portion of the Prostate Biopsies | Baseline to up to 14 days after the last dose | Change (from pre to post-intervention) in CD8+ positive cells in the benign portion of the prostate biopsies |
| Change in CD4+ Positive Cells in the Benign Portion of the Prostate Biopsies | Baseline to up to 14 days after the last dose | Change (from pre to post-intervention) in CD4+ positive cells in the benign portion of the prostate biopsies |
| Change in PD-L1 Positive Cells in the Benign Portion of the Prostate Biopsies | Baseline to up to 14 days after the last dose | Change (from pre to post-intervention) in PD-L1 positive cells in the benign portion of the prostate biopsies |
| Tumor Grade Progression | Baseline to up to 14 days after the last dose | Assessed by the proportion of men with an increase in Gleason score to \>= 4+3 from baseline to post-intervention biopsy. The Gleason score is determined by adding the two most common grades. The Gleason score usually ranges from 6 to 10. Higher numbers indicate a faster growing cancer that is more likely to spread. |
| Change in Tumor Extent | Baseline to up to 14 days after the last dose | Assessed by change (from pre to post-intervention) in percent positive random cores |
| 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 | Change (from pre to post-intervention) in PD-L1 positive cells in the stroma adjacent to tumor and within the malignant portion of the prostate biopsies |
| Size of Dominant MRI Lesion | Up to 14 days after the last dose | The size of dominant MRI lesion. |
| Change in Circulating 15-Mer PSA-specific T Cells | Baseline to up to 14 days after the last dose | Change (from pre to post-intervention) in circulating 15-Mer PSA-specific T cells |
| Change in Soluble Antibodies to Tumor-associated Antigens | Baseline to up to 14 days after the last dose | Change (from pre to post-intervention) in soluble antibodies to tumor-associated antigens |
| Immunologic Effects on the Target Organ Using Multiplex Immunofluorescence | Up to 14 days after the last dose | — |
| Change in International Prostate Symptom Score | Baseline to up to 6 months post-intervention | Change (from baseline to 6 months post-intervention) in International Prostate Symptom Score (IPSS). The IPSS score ranges from 0-35. Higher scores mean a worse symptom. |
| Proportion of Men With no Cancer in the Post-intervention Biopsy | Up to 14 days after the last dose | Assessed by the proportion of patients with no cancer on the post-intervention biopsy |
| Change in Prostate-specific Antigen (PSA) | Baseline to 6 months post-intervention | Change (from baseline to 6 months post-intervention) in prostate-specific antigen (PSA) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Rilimogene-galvacirepvec) 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 | 106 |
| Arm II (Placebo) 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 | 48 |
| Total | 154 |
Baseline characteristics
| Characteristic | Arm I (Rilimogene-galvacirepvec) | Total | Arm II (Placebo) |
|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 7 | 64 years STANDARD_DEVIATION 8 | 64 years STANDARD_DEVIATION 8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants | 5 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 98 Participants | 143 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants | 12 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) White | 91 Participants | 134 Participants | 43 Participants |
| Region of Enrollment United States | 106 participants | 154 participants | 48 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 106 Participants | 154 Participants | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 106 | 0 / 48 |
| other Total, other adverse events | 103 / 106 | 48 / 48 |
| serious Total, serious adverse events | 1 / 106 | 0 / 48 |
Outcome results
Primary
Change in CD4+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies
change (from 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
Population: Participants with tumor present on the tissue sections from both the pre and post-intervention biopsies were included in the analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Rilimogene-galvacirepvec) | Change in CD4+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies | 4.6 number of positive cells per mm^2 | Standard Deviation 166.7 |
| Arm II (Placebo) | Change in CD4+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies | 5.8 number of positive cells per mm^2 | Standard Deviation 261.1 |
Primary
Change in CD8+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies
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.
Time frame: Baseline to up to 14 days after the last dose
Population: Participants with tumor present in tissue sections from both the pre and post-intervention biopsies
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Rilimogene-galvacirepvec) | Change in CD8+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies | 12.2 number of positive cells per mm^2 | Standard Deviation 151.4 |
| Arm II (Placebo) | Change in CD8+ Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies | -6.9 number of positive cells per mm^2 | Standard Deviation 154 |
Secondary
Change in CD4+ Positive Cells in the Benign Portion of the Prostate Biopsies
Change (from pre to post-intervention) in CD4+ positive cells in the benign portion of the prostate biopsies
Time frame: Baseline to up to 14 days after the last dose
Population: Participants with benign tissue present in tissue sections from both the pre and post-intervention biopsies were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Rilimogene-galvacirepvec) | Change in CD4+ Positive Cells in the Benign Portion of the Prostate Biopsies | 73.41 number of positive cells per mm^2 | Standard Deviation 287.74 |
| Arm II (Placebo) | Change in CD4+ Positive Cells in the Benign Portion of the Prostate Biopsies | -19.75 number of positive cells per mm^2 | Standard Deviation 206.59 |
Secondary
Change in CD8+ Positive Cells in the Benign Portion of the Prostate Biopsies
Change (from pre to post-intervention) in CD8+ positive cells in the benign portion of the prostate biopsies
Time frame: Baseline to up to 14 days after the last dose
Population: Participants with benign tissue present in tissue sections from both the pre and post-intervention biopsies were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Rilimogene-galvacirepvec) | Change in CD8+ Positive Cells in the Benign Portion of the Prostate Biopsies | 7.22 number of positive cells per mm^2 | Standard Deviation 202.94 |
| Arm II (Placebo) | Change in CD8+ Positive Cells in the Benign Portion of the Prostate Biopsies | 45.25 number of positive cells per mm^2 | Standard Deviation 198.25 |
Secondary
Change in Circulating 15-Mer PSA-specific T Cells
Change (from pre to post-intervention) in circulating 15-Mer PSA-specific T cells
Time frame: Baseline to up to 14 days after the last dose
Population: Data were not collected.
Secondary
Change in International Prostate Symptom Score
Change (from baseline to 6 months post-intervention) in International Prostate Symptom Score (IPSS). The IPSS score ranges from 0-35. Higher scores mean a worse symptom.
Time frame: Baseline to up to 6 months post-intervention
Population: The initial protocol did not include participant follow-up at 6 months post-intervention. Participants with available IPSS data at baseline and at 6 months post-intervention were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Rilimogene-galvacirepvec) | Change in International Prostate Symptom Score | -0.12 score on a scale | Standard Deviation 4.67 |
| Arm II (Placebo) | Change in International Prostate Symptom Score | 0.87 score on a scale | Standard Deviation 3.57 |
Secondary
Change in PD-L1 Positive Cells in the Benign Portion of the Prostate Biopsies
Change (from pre to post-intervention) 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
Population: Data were not obtained.
Secondary
Change in PD-L1 Positive Cells in the Stroma Adjacent to Tumor and Within the Malignant Portion of the Prostate Biopsies
Change (from pre to post-intervention) 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
Population: Data were not obtained.
Secondary
Change in Prostate-specific Antigen (PSA)
Change (from baseline to 6 months post-intervention) in prostate-specific antigen (PSA)
Time frame: Baseline to 6 months post-intervention
Population: The initial protocol did not include participant follow-up at 6 months post-intervention. Participants with available PSA data at baseline and at 6 months post-intervention were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Rilimogene-galvacirepvec) | Change in Prostate-specific Antigen (PSA) | 0.26 ng/ml | Standard Deviation 2.36 |
| Arm II (Placebo) | Change in Prostate-specific Antigen (PSA) | -0.66 ng/ml | Standard Deviation 3.49 |
Secondary
Change in Soluble Antibodies to Tumor-associated Antigens
Change (from pre to post-intervention) in soluble antibodies to tumor-associated antigens
Time frame: Baseline to up to 14 days after the last dose
Population: Data were not collected.
Secondary
Change in Tumor Extent
Assessed by change (from pre to post-intervention) in percent positive random cores
Time frame: Baseline to up to 14 days after the last dose
Population: The number of participants analyzed is different from the numbers provided in the Participant Flow Module because 2 participants in the placebo arm did not undergo the post-intervention biopsy to provide the data for the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I (Rilimogene-galvacirepvec) | Change in Tumor Extent | -1.7 percentage of total cores | Standard Deviation 16.1 |
| Arm II (Placebo) | Change in Tumor Extent | 1.6 percentage of total cores | Standard Deviation 15.2 |
Secondary
Immunologic Effects on the Target Organ Using Multiplex Immunofluorescence
Time frame: Up to 14 days after the last dose
Population: Data were not collected.
Secondary
Proportion of Men With no Cancer in the Post-intervention Biopsy
Assessed by the proportion of patients with no cancer on the post-intervention biopsy
Time frame: Up to 14 days after the last dose
Population: The number of participants analyzed is different from the numbers provided in the Participant Flow Module because 2 participants in the placebo arm did not undergo the post-intervention biopsy to provide the data for the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Rilimogene-galvacirepvec) | Proportion of Men With no Cancer in the Post-intervention Biopsy | 25 Participants |
| Arm II (Placebo) | Proportion of Men With no Cancer in the Post-intervention Biopsy | 8 Participants |
Secondary
Size of Dominant MRI Lesion
The size of dominant MRI lesion.
Time frame: Up to 14 days after the last dose
Population: Data were not collected.
Secondary
Tumor Grade Progression
Assessed by the proportion of men with an increase in Gleason score to \>= 4+3 from baseline to post-intervention biopsy. The Gleason score is determined by adding the two most common grades. The Gleason score usually ranges from 6 to 10. Higher numbers indicate a faster growing cancer that is more likely to spread.
Time frame: Baseline to up to 14 days after the last dose
Population: The number of participants analyzed is different from the numbers provided in the Participant Flow Module because 2 participants in the placebo arm did not undergo the post-intervention biopsy to provide the data for the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I (Rilimogene-galvacirepvec) | Tumor Grade Progression | 8 Participants |
| Arm II (Placebo) | Tumor Grade Progression | 6 Participants |