metastatic castration-resistant prostate cancer MedDRA version: 21.1 Level: PT Classification code 10036909 Term: Prostate cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10036920 Term: Prostate cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10076506 Term:
Conditions
Interventions
Trade Name: Opdivo
Product Name: Nivolumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Nivolumab
Other descriptive name: NIVOLUMAB
Concentration unit: mg/ml millig
Sponsors
Department of Oncology, Herlev & Gentofte Hospital
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Have a signed Independent Ethics Committee (IEC)-approved informed consent form prior to any study-specific evaluation. Subjects must be willing and able to comply with scheduled visits, treatment schedule, lab testing and other requirements of the study. 2. Male =18 years of age at the time consent form is signed 3. Have a histologically or cytologically confirmed adenocarcinoma or poorly differentiated carcinoma of the prostate (pure small-cell histology or pure high-grade neuroendocrine histology are excluded; neuroendocrine differentiation is allowed) 4. If possible, metastases accessible for image-guided percutaneous biopsies will be acquired, if assessed as safe for the patient 5. Surgically or medically castrated, with serum testosterone levels 100 x 109/L iii. Hemoglobin=9 g/dL (5.6 mmol/L) independent of transfusion within 14 days b. Hepatic function: i. Asparatate aminotransferase (AST) and alanine aminotransferase (ALT) =65 years) yes F.1.3.1 Number of
Exclusion criteria
Exclusion criteria: 1.Active malignancy, with the exception of curatively treated non-melanoma skin cancer, carcinoma in situ, or superficial bladder cancer - Patients with a history of malignancy that has been completely treated, and currently with no evidence of that cancer, are permitted to be enrolled in the trial provided all chemotherapy was completed > 6 months prior and/or bone marrow transplant >2years prior to first dose of ipilimumab and nivolumab 2.Prior therapy with an anti-PD1, anti-PD-L1, anti-CD137 or anti-CTLA4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. 3. Symptomatic and/or untreated central nervous system (CNS) metastases. Patients with asymptomatic, previously treated CNS metastases are eligible provided they have been clinically stable, ie not requiring steroids for at least 4 weeks prior to first dose of ipilimumab and nivolumab and have had appropriate scans screening assessments 4. Symptomatic or impending spinal cord compression unless appropriately treated, clinically stable and asymptomatic 5. If patient have an active known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type 1 diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment or conditions not expected to recur in the absence of an external trigger 6. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness or history of chronic hepatitis B or C. 7. Received treatment with chemotherapy, hormonal therapy (with the exception of LHRH analog), radiation, antibody therapy or immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors or experimental drugs within 4 weeks prior to first dose of ipilimumab and nivolumab 8. Adverse effect of prior therapy not resolved to CTCAE Grade 1 or below with the exception of alopecia. Ongoing Grade 2 non-hematologic toxicity related to most recent treatment regimen may be permitted with prior advanced approval from the sponsor 9. Initiated denosumab or bisphosphonate therapy or adjusted denosumab or bisphosphonate dose/regimen within 4 weeks prior to first dose of ipilimumab and nivolumab. Patients on stable denosumab or bisphosphonate regimen are eligible and may continue treatment 10. Non-study related minor surgery procedure 10mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses>10mg daily prednisone equivalents are permitted in the absence of active autoimmune disease 14. As there is a potential risk for hepatic toxicity with nivolumab/ipilimumab combinations, drugs with a predisposition to hepatotoxicity should be used with caution in patients treated with nivolumab/ipilimumab cont
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the response rate of immune checkpoint inhibition, ipilimumab and nivolumab in combination with SBRT and compare to combination immunotherapy with ipilimumab and nivolumab.;Secondary Objective: Secondary objective: Study safety, quality of life (QoL), and efficacy defined as CBR, rPFS and OS. Exploratory objective: To describe changes in tumor tissue and blood before, during and after immunotherapy and investigate immune related biomarkers. Investigate the association between biomarkers in blood and tumor tissue and outcomes ;Primary end point(s): Coprimary endpoints: -Objective response-rate according to RECIST1.1 per PCWG3 criteria (for patients with measurable disease) -Prostate-specific antigen (PSA) response-rate of = 50% decline from baseline at any time from treatment start (confirmed after = 3 weeks, all patients with measurable and non-measurable disease);Timepoint(s) of evaluation of this end point: Due to the two-stage design of trial, the first analysis of CBR is done after first 40 patients (20 in each arm) are randomised and at least 6 months have elapsed since randomisation. Final analysis will be done at least 6 months have elapsed from the completion of enrollment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety per CTCAE v5.0, radiographic progression-free survival (rPFS) defined as per PCWG3 and clinical progression (all patients), rPFS per iRECIST, CBR as defined by RECIST 1.1 and iRECIST (stable disease (SD) for ? 6 months, partial response (PR), complete response (CR), ORR by iRECIST, duration of response (DoR), PSA-PFS beyond 12 weeks per PCWG3, rPFS rate and OS rate at 6 months and 1 year, OS, quality of life using EORTC QLQ-C30;Timepoint(s) of evaluation of this end point: Secondary endpoints will be analysed after LVLS. However, safety will be evaluated continously during the trial. | — |
Countries
Denmark
Contacts
Public ContactPI Rikke Løvendahl Eefsen
Department of Oncology, Herlev & Gentofte Hospital
Outcome results
None listed