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.
Clinical Trials /
Neoadjuvant Dupilumab in Men With Localized High-Risk Prostate Cancer
NCT03886493
Related Conditions:
- Prostate Adenocarcinoma
Recruiting Status:
Terminated
Phase:
Phase 2
Trial Eligibility
Document
Title
- Brief Title: Neoadjuvant Dupilumab in Men With Localized High-Risk Prostate Cancer
- Official Title: Neoadjuvant Dupilumab in Men With Localized High-Risk Prostate Cancer
Clinical Trial IDs
- ORG STUDY ID: J18116
- SECONDARY ID: IRB00182718
- NCT ID: NCT03886493
Conditions
- Prostate Cancer
Interventions
| Drug | Synonyms | Arms |
|---|---|---|
| Dupilumab | Dupixent | Dupixent Subcutaneous (SQ) Injection |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|---|---|---|
| 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. |
|
Eligibility Criteria
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Male |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Change in M2-TAM infiltration from baseline |
| Time Frame: | change from baseline to up to 59 days post-intervention |
| Safety Issue: | |
| Description: | 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 Outcome Measures
| Measure: | Safety as assessed by number of participants experiencing adverse events |
| Time Frame: | up to 59 days post-intervention |
| Safety Issue: | |
| Description: | Adverse events defined by NCI Common Toxicity Criteria version 4.0 (NCI CTCAE v4.0) |
| Measure: | 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 |
| Safety Issue: | |
| Description: |
| Measure: | 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 |
| Safety Issue: | |
| Description: |
| Measure: | 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 |
| Safety Issue: | |
| Description: |
| Measure: | CD8+ T-cell infiltration in post-treatment prostate glands |
| Time Frame: | up to 59 days post-intervention |
| Safety Issue: | |
| Description: | mean CD4+ T-cell staining percentage and CD4+/Treg ratio in harvested tumor tissue collected from prostatectomy specimen |
| Measure: | CD4+ T-cell and Treg infiltration in post-treatment prostate glands |
| Time Frame: | up to 59 days post-intervention |
| Safety Issue: | |
| Description: | mean CD4+ T-cell staining percentage and CD4+/Treg ratio in harvested tumor tissue collected from prostatectomy specimen |
| Measure: | Expression of apoptosis marker (Annexin V) in post-treatment prostate tumor specimen as measured by mean staining percentage in tumor tissue |
| Time Frame: | up to 59 days post-intervention |
| Safety Issue: | |
| Description: | Mean staining percentage of Annexin V in tumor tissue, using TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) staining. |
| Measure: | 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 |
| Safety Issue: | |
| Description: |
| Measure: | Proportion of participants with pathological complete response |
| Time Frame: | 1 month post-prostatectomy |
| Safety Issue: | |
| Description: | Pathological response is defined as the absence of tumor identification by study pathologist on standard histological analysis of resected prostate specimens. |
| Measure: | Proportion of participants who achieve an undetectable PSA at 2 months post-prostatectomy |
| Time Frame: | 2 months post-prostatectomy |
| Safety Issue: | |
| Description: | Proportion of participants with PSA <0.1ng/mL by 2 months after prostatectomy |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins |
Trial Keywords
- high-risk prostate cancer
- localized prostate cancer
- prior to prostatectomy
- neoadjuvant
Last Updated
October 14, 2020
