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| ID | Type | Description | Link |
|---|---|---|---|
| IRB00182718 | Other Identifier | JHM IRB |
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Low accrual due to COVID-19 pandemic.
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| Name | Class |
|---|---|
| Regeneron Pharmaceuticals | INDUSTRY |
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This is a single-center, single arm, open-label phase II study evaluating the safety, anti-tumor effect, and immunogenicity of neoadjuvant Dupixent given prior to radical prostatectomy.
This is a single-center, single arm, open-label phase II study evaluating the safety, anti-tumor effect, and immunogenicity of neoadjuvant Dupixent given prior to radical prostatectomy in men with high-risk localized prostate cancer (this trial will enroll men with at least high risk prostate cancer defined by NCCN Guidelines Version 2.2017 = clinical stage ≥T3a or PSA >20 ng/mL or Gleason score ≥8).
Patients will be recruited from the outpatient Urology clinic. Men will be treated with dupilumab 600 mg subcutaneously (SQ) on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43. They will then undergo surgery on day 57. 14 days after the last dose of Dupixent, prostate glands will be harvested at the time of radical prostatectomy, and prostate tissue will be examined for the secondary endpoints.
Follow-up evaluation for adverse events will occur 30 days and 60 days after surgery. Patients will then be followed by their urologists according to standard institutional practices, but will require PSA evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dupixent Subcutaneous (SQ) Injection | Experimental | Participants will be treated with dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43. They will then undergo surgery on day 57. 14 days after the last dose of Dupixent, prostate glands will be harvested at the time of radical prostatectomy, and prostate tissue will be examined for the secondary endpoints. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dupilumab | Drug | dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in M2-TAM Infiltration From Baseline | Change in M2-TAM infiltration (number of macrophages / cell nuclei per high power field [hpf]) measured in pre- dupilumab biopsy to M2-TAM infiltration measured in post-dupilumab specimen collected at time of radical prostatectomy (up to 59 days post-intervention). Degree of TAM infiltration will be analyzed using immunohistochemical staining for CD206. It is hypothesized that a positive value will be associated with better outcome and a negative value will reflect a worse outcome. | change from baseline to up to 59 days post-intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Safety as Assessed by Number of Participants Experiencing Adverse Events | Adverse events defined by NCI Common Toxicity Criteria version 4.0 (NCI CTCAE v4.0) | up to 59 days post-intervention |
| Feasibility as Assessed by Number of Participants Who Have an Average Blood Loss in Excess of 2500 mL During Prostatectomy |
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Inclusion Criteria:
To be eligible for this study, patients must meet all of the following criteria:
Histologically confirmed adenocarcinoma of the prostate (clinical stage T1c-T3b, N0, M0) without involvement of lymph nodes, bone, or visceral organs
Initial prostate biopsy is available for central pathologic review, and is confirmed to show at least 2 positive cores and a Gleason sum of ≥7
Radical prostatectomy has been scheduled at Johns Hopkins Hospital
Age ≥18 years
Eastern Cooperative Oncology Group (ECOG) performance status 0-1, or Karnofsky score ≥ 70%
Adequate bone marrow, hepatic, and renal function:
Willingness to provide written informed consent and HIPAA authorization for the release of personal health information, and the ability to comply with the study requirements (note: HIPAA authorization will be included in the informed consent)
Willingness to use barrier contraception from the time of first dose of DUPILUMAB until the time of prostatectomy.
Exclusion Criteria:
To be eligible for this study, patients should not meet any of the following criteria:
Subjects must have a prostate in order to be eligible for this trial.
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| Name | Affiliation | Role |
|---|---|---|
| Kenneth Pienta, MD | Johns Hopkins University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Johns Hopkins Sidney Kimmel Comprehensive Cancer Center | Baltimore | Maryland | 21228 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Dupixent Subcutaneous (SQ) Injection | Participants will be treated with dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43. They will then undergo surgery on day 57. 14 days after the last dose of Dupixent, prostate glands will be harvested at the time of radical prostatectomy, and prostate tissue will be examined for the secondary endpoints. Dupilumab: dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Dupixent Subcutaneous (SQ) Injection | Participants will be treated with dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43. They will then undergo surgery on day 57. 14 days after the last dose of Dupixent, prostate glands will be harvested at the time of radical prostatectomy, and prostate tissue will be examined for the secondary endpoints. Dupilumab: dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in M2-TAM Infiltration From Baseline | Change in M2-TAM infiltration (number of macrophages / cell nuclei per high power field [hpf]) measured in pre- dupilumab biopsy to M2-TAM infiltration measured in post-dupilumab specimen collected at time of radical prostatectomy (up to 59 days post-intervention). Degree of TAM infiltration will be analyzed using immunohistochemical staining for CD206. It is hypothesized that a positive value will be associated with better outcome and a negative value will reflect a worse outcome. | Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions. | Posted | change from baseline to up to 59 days post-intervention |
|
up to 1 year
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dupixent Subcutaneous (SQ) Injection | Participants will be treated with dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43. They will then undergo surgery on day 57. 14 days after the last dose of Dupixent, prostate glands will be harvested at the time of radical prostatectomy, and prostate tissue will be examined for the secondary endpoints. Dupilumab: dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Urinary incontinence | Renal and urinary disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kenneth Pienta, M.D. | Johns Hopkins University School of Medicine | 410-502-3137 | kpienta1@jhmi.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 3, 2020 | Sep 17, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C582203 | dupilumab |
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Men will be treated with dupilumab 600 mg s.q. on day 1, and then 300 mg s.q. on days 8,15, 22, 29, 36, 43. They will then undergo surgery on day 57. Fourteen days after the last dose of Dupixent, prostate glands will be harvested at the time of radical prostatectomy, and prostate tissue will be examined for the secondary endpoints. Follow-up evaluation for adverse events will occur 30 days and 60 days after surgery. Patients will then be followed by their urologists according to standard institutional practices, but will require PSA evaluations every 3 (±1) months during year 1 and every 6 (±2) months during years 2-3.
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| up to 59 days post-intervention |
| Feasibility as Assessed by Number of Participants With Average Prostatectomy Operative Time in Excess of 3.5 Hours | up to 59 days post-intervention |
| Feasibility as Assessed by Number of Participants With Average Hospital Stay in Excess of 4 Days Post-prostatectomy | up to 59 days post-intervention |
| CD8+ T-cell Infiltration in Post-treatment Prostate Glands | mean CD4+ T-cell staining percentage and CD4+/Treg ratio in harvested tumor tissue collected from prostatectomy specimen | up to 59 days post-intervention |
| CD4+ T-cell and Treg Infiltration in Post-treatment Prostate Glands | mean CD4+ T-cell staining percentage and CD4+/Treg ratio in harvested tumor tissue collected from prostatectomy specimen | up to 59 days post-intervention |
| Expression of Apoptosis Marker (Annexin V) in Post-treatment Prostate Tumor Specimen as Measured by Mean Staining Percentage in Tumor Tissue | Mean staining percentage of Annexin V in tumor tissue, using TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) staining. | up to 59 days post-intervention |
| Expression of Cell Proliferation in Post-treatment Prostate Tumor Specimen as Measured by Mean Staining Percentage of Ki-67 in Tumor Tissue | up to 59 days post-intervention |
| Proportion of Participants With Pathological Complete Response | Pathological response is defined as the absence of tumor identification by study pathologist on standard histological analysis of resected prostate specimens. | 1 month post-prostatectomy |
| Proportion of Participants Who Achieve an Undetectable PSA at 2 Months Post-prostatectomy | Proportion of participants with PSA <0.1ng/mL by 2 months after prostatectomy | 2 months post-prostatectomy |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
| Secondary | Safety as Assessed by Number of Participants Experiencing Adverse Events | Adverse events defined by NCI Common Toxicity Criteria version 4.0 (NCI CTCAE v4.0) | Posted | Count of Participants | Participants | up to 59 days post-intervention |
|
|
|
| Secondary | Feasibility as Assessed by Number of Participants Who Have an Average Blood Loss in Excess of 2500 mL During Prostatectomy | Only 6/7 participants had a prostatectomy. | Posted | Count of Participants | Participants | up to 59 days post-intervention |
|
|
|
| Secondary | Feasibility as Assessed by Number of Participants With Average Prostatectomy Operative Time in Excess of 3.5 Hours | Only 6/7 participants had a prostatectomy. | Posted | Count of Participants | Participants | up to 59 days post-intervention |
|
|
|
| Secondary | Feasibility as Assessed by Number of Participants With Average Hospital Stay in Excess of 4 Days Post-prostatectomy | Only 6/7 participants had a prostatectomy | Posted | Count of Participants | Participants | up to 59 days post-intervention |
|
|
|
| Secondary | CD8+ T-cell Infiltration in Post-treatment Prostate Glands | mean CD4+ T-cell staining percentage and CD4+/Treg ratio in harvested tumor tissue collected from prostatectomy specimen | Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions. | Posted | up to 59 days post-intervention |
|
|
| Secondary | CD4+ T-cell and Treg Infiltration in Post-treatment Prostate Glands | mean CD4+ T-cell staining percentage and CD4+/Treg ratio in harvested tumor tissue collected from prostatectomy specimen | Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions. | Posted | up to 59 days post-intervention |
|
|
| Secondary | Expression of Apoptosis Marker (Annexin V) in Post-treatment Prostate Tumor Specimen as Measured by Mean Staining Percentage in Tumor Tissue | Mean staining percentage of Annexin V in tumor tissue, using TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) staining. | Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions. | Posted | up to 59 days post-intervention |
|
|
| Secondary | Expression of Cell Proliferation in Post-treatment Prostate Tumor Specimen as Measured by Mean Staining Percentage of Ki-67 in Tumor Tissue | Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions. | Posted | up to 59 days post-intervention |
|
|
| Secondary | Proportion of Participants With Pathological Complete Response | Pathological response is defined as the absence of tumor identification by study pathologist on standard histological analysis of resected prostate specimens. | Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions. | Posted | 1 month post-prostatectomy |
|
|
| Secondary | Proportion of Participants Who Achieve an Undetectable PSA at 2 Months Post-prostatectomy | Proportion of participants with PSA <0.1ng/mL by 2 months after prostatectomy | Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions. | Posted | 2 months post-prostatectomy |
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 7 |
| 7 |
| Headache, intermittent | General disorders | Non-systematic Assessment |
|
| Bloating | Gastrointestinal disorders | Non-systematic Assessment |
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| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
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| edema in right calf and ankle | Blood and lymphatic system disorders | Non-systematic Assessment |
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| elevated hemoglobin | Blood and lymphatic system disorders | Non-systematic Assessment |
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| eye pain | Eye disorders | Non-systematic Assessment |
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| Fatigue | General disorders | Non-systematic Assessment |
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| Vivid dreams | General disorders | Non-systematic Assessment |
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| hyperkalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| hypocalcemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| hypoglycemia | Metabolism and nutrition disorders | Non-systematic Assessment |
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| Increased creatinine | Renal and urinary disorders | Non-systematic Assessment |
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| induration at injection site on abdomen | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| laryngeal inflammation | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| loss of appetite | Metabolism and nutrition disorders | Non-systematic Assessment |
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| maculo papular rash on abdomen | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| nausea | Gastrointestinal disorders | Non-systematic Assessment |
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| pruritis at site of injection on abdomen | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| reproductive system disorder, other blood in ejaculate | Reproductive system and breast disorders | Non-systematic Assessment |
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| Right AC bruising related to blood draw | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| Skin ulceration upper lip | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| toothache | Gastrointestinal disorders | Non-systematic Assessment |
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| urinary retention | Renal and urinary disorders | Non-systematic Assessment |
|
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| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |