Neoadjuvant Dupilumab in Men With Localized High-Risk Prostate Cancer

NCT03886493 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: J18116IRB00182718
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Prostate Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  change from baseline to up to 59 days post-intervention

Secondary Outcomes (10)

• Safety as Assessed by Number of Participants Experiencing Adverse Events

  up to 59 days post-intervention

• 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

Study Arms (1)

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.

Drug: Dupilumab

Interventions

Dupilumab DRUG

dupilumab 600 mg SQ on day 1, and then 300 mg SQ on days 8,15, 22, 29, 36, 43.

Also known as: Dupixent

Dupixent Subcutaneous (SQ) Injection

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: Subjects must have a prostate in order to be eligible for this trial.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (1)

Johns Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21228, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

dupilumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Kenneth Pienta, M.D.
• Organization: Johns Hopkins University School of Medicine

kpienta1@jhmi.edu

410-502-3137

Study Officials

• Kenneth Pienta, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 20, 2019
• First Posted: March 22, 2019
• Study Start: August 28, 2019
• Primary Completion: October 6, 2020
• Study Completion: October 6, 2020
• Last Updated: October 15, 2021
• Results First Posted: October 15, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)