Prostate Cancer
Conditions
Keywords
high-risk prostate cancer, localized prostate cancer, prior to prostatectomy, neoadjuvant
Brief summary
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.
Detailed description
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.
Interventions
DRUGDupilumab
dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43.
Sponsors
Regeneron Pharmaceuticals
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
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.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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: * WBC \>3,000 cells/mm3 * ANC \>1,500 cells/mm3 * Hemoglobin \>9.0 g/dL * Platelet count \>100,000 cells/mm3 * Serum creatinine \<3 × upper limit of normal (ULN) * Serum bilirubin \<3 × ULN * ALT \<5 × ULN * AST \<5 × ULN * Alkaline phosphatase \<5 × ULN * 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: * Presence of known lymph node involvement or distant metastases * Other histologic types of prostate cancers such as ductal, sarcomatous, lymphoma, small cell, and neuroendocrine tumors * Prior radiation therapy, hormonal therapy, biologic therapy, or chemotherapy for prostate cancer * Prior immunotherapy/vaccine therapy for prostate cancer * Concomitant treatment with other hormonal therapy or 5α-reductase inhibitors * Current use of systemic corticosteroids or use of corticosteroids within 4 weeks of enrollment (inhaled corticosteroids for asthma or COPD are permitted) * Use of experimental agents for prostate cancer within the past 3 months from time of screening * History or presence of autoimmune disease requiring systemic immunosuppression (including but not limited to: inflammatory bowel disease, systemic lupus erythematosus, vasculitis, rheumatoid arthritis, scleroderma, multiple sclerosis, hemolytic anemia, Sjögren syndrome, and sarcoidosis) * History of malignancy within the last 3 years, with the exception of non-melanoma skin cancers and superficial bladder cancer * Uncontrolled major active infectious, cardiovascular, pulmonary, hematologic, or psychiatric illnesses that would make the patient a poor study candidate * Known prior or current history of HIV and/or hepatitis B/C * Significant eye disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in M2-TAM Infiltration From Baseline | change from baseline to up to 59 days post-intervention | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility as Assessed by Number of Participants Who Have an Average Blood Loss in Excess of 2500 mL During Prostatectomy | 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 | up to 59 days post-intervention | mean CD4+ T-cell staining percentage and CD4+/Treg ratio in harvested tumor tissue collected from prostatectomy specimen |
| Safety as Assessed by Number of Participants Experiencing Adverse Events | up to 59 days post-intervention | Adverse events defined by NCI Common Toxicity Criteria version 4.0 (NCI CTCAE v4.0) |
| Expression of Apoptosis Marker (Annexin V) in Post-treatment Prostate Tumor Specimen as Measured by Mean Staining Percentage in Tumor Tissue | up to 59 days post-intervention | Mean staining percentage of Annexin V in tumor tissue, using TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) staining. |
| 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 | 1 month post-prostatectomy | Pathological response is defined as the absence of tumor identification by study pathologist on standard histological analysis of resected prostate specimens. |
| Proportion of Participants Who Achieve an Undetectable PSA at 2 Months Post-prostatectomy | 2 months post-prostatectomy | Proportion of participants with PSA \<0.1ng/mL by 2 months after prostatectomy |
| CD4+ T-cell and Treg Infiltration in Post-treatment Prostate Glands | up to 59 days post-intervention | mean CD4+ T-cell staining percentage and CD4+/Treg ratio in harvested tumor tissue collected from prostatectomy specimen |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Dupixent Subcutaneous (SQ) Injection |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Region of Enrollment United States | 7 Participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
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.
Time frame: change from baseline to up to 59 days post-intervention
Population: Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions.
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
Time frame: up to 59 days post-intervention
Population: Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions.
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
Time frame: up to 59 days post-intervention
Population: Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions.
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.
Time frame: up to 59 days post-intervention
Population: Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions.
Secondary
Expression of Cell Proliferation in Post-treatment Prostate Tumor Specimen as Measured by Mean Staining Percentage of Ki-67 in Tumor Tissue
Time frame: up to 59 days post-intervention
Population: Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions.
Secondary
Feasibility as Assessed by Number of Participants Who Have an Average Blood Loss in Excess of 2500 mL During Prostatectomy
Time frame: up to 59 days post-intervention
Population: Only 6/7 participants had a prostatectomy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dupixent Subcutaneous (SQ) Injection | Feasibility as Assessed by Number of Participants Who Have an Average Blood Loss in Excess of 2500 mL During Prostatectomy | 0 Participants |
Secondary
Feasibility as Assessed by Number of Participants With Average Hospital Stay in Excess of 4 Days Post-prostatectomy
Time frame: up to 59 days post-intervention
Population: Only 6/7 participants had a prostatectomy
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dupixent Subcutaneous (SQ) Injection | Feasibility as Assessed by Number of Participants With Average Hospital Stay in Excess of 4 Days Post-prostatectomy | 0 Participants |
Secondary
Feasibility as Assessed by Number of Participants With Average Prostatectomy Operative Time in Excess of 3.5 Hours
Time frame: up to 59 days post-intervention
Population: Only 6/7 participants had a prostatectomy.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dupixent Subcutaneous (SQ) Injection | Feasibility as Assessed by Number of Participants With Average Prostatectomy Operative Time in Excess of 3.5 Hours | 2 Participants |
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
Time frame: 2 months post-prostatectomy
Population: Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions.
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.
Time frame: 1 month post-prostatectomy
Population: Data could not be collected for this outcome measure due to COVID-19 pandemic restrictions.
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)
Time frame: up to 59 days post-intervention
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Dupixent Subcutaneous (SQ) Injection | Safety as Assessed by Number of Participants Experiencing Adverse Events | 7 Participants |