Dupilumab before Surgery in Treating Men with Localized High-Risk Prostate Cancer
This phase II trial studies how well dupilumab, when given before surgery, works in treating men with high risk prostate cancer that has not spread to other parts of the body (localized). Immunotherapy with monoclonal antibodies, such as dupilumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Inclusion 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
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1, or Karnofsky score >= 70%
- White blood cell count (WBC) > 3,000 cells/mm^3
- Absolute neutrophil count (ANC) > 1,500 cells/mm^3
- Hemoglobin > 9.0 g/dL
- Platelet count > 100,000 cells/mm^3
- Serum creatinine < 3 x upper limit of normal (ULN)
- Serum bilirubin < 3 x ULN
- Alanine aminotransferase (ALT) < 5 x ULN
- Aspartate Aminotransferase (AST) < 5 x ULN
- Alkaline phosphatase < 5 x ULN
- Willingness to provide written informed consent and Health Insurance Portability and Accountability Act (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
- 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 5 alpha-reductase inhibitors
- Current use of systemic corticosteroids or use of corticosteroids within 4 weeks of enrollment (inhaled corticosteroids for asthma or chronic obstructive pulmonary disease [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, Sjogren 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 human immunodeficiency virus (HIV) and/or hepatitis B/C
- Significant eye disease
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT03886493.
PRIMARY OBJECTIVE:
I. Evaluate the ability of dupilumab to inhibit M2-tumor-associated macrophages (TAMs) infiltration or prostate cancer by comparison of pre-dupilumab M2-TAM infiltration in the biopsy versus (vs.) post-dupilumab M2-TAM infiltration in the radical prostatectomy (RP) specimen.
SECONDARY OBJECTIVES:
I. To evaluate the safety and tolerability of dupilumab administered 600 mg subcutaneously (s.q.) on day 1, and then 300 mg s.q. on days 8,15, 22, 29, 36, 43.
II. To evaluate the feasibility of administering dupilumab administered 600 mg s.q. on day 1, and then 300 mg s.q. on days 8,15, 22, 29, 36, 43.
III. Quantify the extent of CD8+ T cell infiltration into the prostate from harvested prostate glands of treated patients.
IV. Quantify the extent of CD4+ T cell and T-regulator lymphocyte (Treg) infiltration into the prostate in prostate specimens of treated patients.
V. Quantify markers of apoptosis in prostate tumor specimens of treated patients using TdT-mediated deoxy uridine triphosphate (UTP) nick end-labeling assay (TUNEL) staining and expressed as the mean staining percentage in tumor tissue.
VI. Quantify markers of cell proliferation in prostate tumor specimens of treated patients using Ki-67 staining and expressed by the mean staining percentage in tumor.
VII. Evaluate the proportion of pathological complete responses in prostate tumor specimens of treated patients.
VIII. Evaluate prostate specific antigen (PSA) response rates defined as the proportion of patients who achieve an undetectable PSA (< 0.1 ng/mL) by 2 months after prostatectomy.
OUTLINE:
Patients receive dupilumab subcutaneously (SC) once daily (QD) on days 1, 8, 15, 22, 29, 36, and 43 in the absence of disease progression or unacceptable toxicity. Patients then undergo radical prostatectomy on day 57.
After completion of study treatment, patients are followed up at 30 and 60 days, every 3 months for 1 year, and every 6 months for up to 2 years.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationJohns Hopkins University/Sidney Kimmel Cancer Center
Principal InvestigatorKenneth James Pienta
- Primary IDJ18116
- Secondary IDsNCI-2019-04692, CRMS-69849, IRB00182718
- ClinicalTrials.gov IDNCT03886493