Clinical Trials /

Neoadjuvant Dupilumab in Men With Localized High-Risk Prostate Cancer

NCT03886493

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.

Related Conditions:
  • Prostate Adenocarcinoma
Recruiting Status:

Recruiting

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

DrugSynonymsArms
DupilumabDupixentDupixent 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

NameTypeDescriptionInterventions
Dupixent Subcutaneous (SQ) InjectionExperimentalParticipants 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

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:Recruiting
Lead Sponsor:Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Trial Keywords

  • high-risk prostate cancer
  • localized prostate cancer
  • prior to prostatectomy
  • neoadjuvant

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