Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Neoadjuvant Dupilumab in Men With Localized High-Risk Prostate Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03886493
Recruitment Status : Not yet recruiting
First Posted : March 22, 2019
Last Update Posted : April 25, 2019
Sponsor:
Collaborator:
Regeneron Pharmaceuticals
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Dupilumab Phase 2

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Dupilumab in Men With Localized High-Risk Prostate Cancer
Estimated Study Start Date : May 2019
Estimated Primary Completion Date : February 15, 2020
Estimated Study Completion Date : February 15, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
Drug Information available for: Dupilumab

Arm Intervention/treatment
Experimental: 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.
Drug: Dupilumab
dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43.
Other Name: Dupixent




Primary Outcome Measures :
  1. Change in M2-TAM infiltration from baseline [ Time Frame: 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 Outcome Measures :
  1. Safety as assessed by number of participants experiencing adverse events [ Time Frame: up to 59 days post-intervention ]
    Adverse events defined by NCI Common Toxicity Criteria version 4.0 (NCI CTCAE v4.0)

  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. CD8+ T-cell infiltration in post-treatment prostate glands [ Time Frame: up to 59 days post-intervention ]
    mean CD4+ T-cell staining percentage and CD4+/Treg ratio in harvested tumor tissue collected from prostatectomy specimen

  6. CD4+ T-cell and Treg infiltration in post-treatment prostate glands [ Time Frame: up to 59 days post-intervention ]
    mean CD4+ T-cell staining percentage and CD4+/Treg ratio in harvested tumor tissue collected from prostatectomy specimen

  7. 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 ]
    Mean staining percentage of Annexin V in tumor tissue, using TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) staining.

  8. 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 ]
  9. Proportion of participants with pathological complete response [ Time Frame: 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.

  10. Proportion of participants who achieve an undetectable PSA at 2 months post-prostatectomy [ Time Frame: 2 months post-prostatectomy ]
    Proportion of participants with PSA <0.1ng/mL by 2 months after prostatectomy



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Subjects must have a prostate in order to be eligible for this trial.
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03886493


Contacts
Layout table for location contacts
Contact: Carolyn Chapman, RN 443-287-7841 cchapma7@jhmi.edu
Contact: Alice Jordan, MS 410-955-1239 ajorda30@jhmi.edu

Locations
Layout table for location information
United States, Maryland
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center Not yet recruiting
Baltimore, Maryland, United States, 21228
Contact: Carolyn Chapman, RN    443-287-7841    cchapma7@jhmi.edu   
Principal Investigator: Kenneth Pienta, MD         
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Regeneron Pharmaceuticals
Investigators
Layout table for investigator information
Principal Investigator: Kenneth Pienta, MD Johns Hopkins University

Layout table for additonal information
Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT03886493     History of Changes
Other Study ID Numbers: J18116
IRB00182718 ( Other Identifier: JHM IRB )
First Posted: March 22, 2019    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: April 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
high-risk prostate cancer
localized prostate cancer
prior to prostatectomy
neoadjuvant

Additional relevant MeSH terms:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs