Clinical trial NCT03886493: Neoadjuvant Dupilumab in Men With Localized High-Risk Prostate Cancer
Official title: Neoadjuvant Dupilumab in Men With Localized High-Risk Prostate Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: high-risk prostate cancer
localized prostate cancer
prior to prostatectomy
neoadjuvant
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2019-03-22
Enrollment: 7
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in M2-TAM Infiltration From Baseline
timeFrame: change from baseline to up to 59 days post-intervention
Secondary outcomes:
measure: Safety as Assessed by Number of Participants Experiencing Adverse Events
timeFrame: up to 59 days post-intervention
measure: Feasibility as Assessed by Number of Participants Who Have an Average Blood Loss in Excess of 2500 mL During Prostatectomy
timeFrame: up to 59 days post-intervention
measure: Feasibility as Assessed by Number of Participants With Average Prostatectomy Operative Time in Excess of 3.5 Hours
timeFrame: up to 59 days post-intervention
measure: Feasibility as Assessed by Number of Participants With Average Hospital Stay in Excess of 4 Days Post-prostatectomy
timeFrame: up to 59 days post-intervention
measure: CD8+ T-cell Infiltration in Post-treatment Prostate Glands
timeFrame: up to 59 days post-intervention
measure: CD4+ T-cell and Treg Infiltration in Post-treatment Prostate Glands
timeFrame: up to 59 days post-intervention
measure: Expression of Apoptosis Marker (Annexin V) in Post-treatment Prostate Tumor Specimen as Measured by Mean Staining Percentage in Tumor Tissue
timeFrame: up to 59 days post-intervention
measure: Expression of Cell Proliferation in Post-treatment Prostate Tumor Specimen as Measured by Mean Staining Percentage of Ki-67 in Tumor Tissue
timeFrame: up to 59 days post-intervention
measure: Proportion of Participants With Pathological Complete Response
timeFrame: 1 month post-prostatectomy
measure: Proportion of Participants Who Achieve an Undetectable PSA at 2 Months Post-prostatectomy
timeFrame: 2 months post-prostatectomy
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Kenneth Pienta, MD
role: PRINCIPAL_INVESTIGATOR
References: