Effect of Ruxolitinib on Tumor Infiltrating Myeloid Cells

Study Overview
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Brief Summary
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Ruxolitinib will be dispensed to patients candidate to prostatectomy immediately after histological diagnosis of prostate adenocarcinoma. The treatment will be given for 28 days followed by a prostatectomy thereafter. Tumor material and blood samples will be analysed before, during and after the treatment with Ruxolitinib.

Detailed Description
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Patients with suspected localized prostate cancer will undergo biopsies spotting different prostate sites, as per standard clinical practice. Patients with histologically confirmed prostate adenocarcinoma and candidate for prostatectomy, after signing the Informed Consent Form, will receive Ruxolitinib for 4 weeks (the time normally elapsing between histological diagnosis and surgery) and will thereafter undergo prostatectomy. Remaining biological material from the diagnosis and the prostatectomy will be sent to the Molecular Oncology Laboratory for molecular analysis. In addition, blood samples will be drawn before, during Ruxolitinib treatment (Week 2), at the end of treatment (Week 4), and after prostatectomy (Week 5), to assess the frequency and subtype of immune subsets and the circulating levels of cytokines and secreted. Patients will be monitored for occurrence of adverse events/surgical complications during treatment and up to 4 weeks after the intervention.

Official Title
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An Exploratory proof-of Mechanism Study to Assess the Effect of Ruxolitinib on Tumor Infiltrating Myeloid Cells and Additional Immune Subsets in Prostate Cancer Patients

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Ruxolitinib 20 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years Histological diagnosis of prostate adenocarcinoma Stage ≥T2b for which surgery is indicated No distant metastasis (M0) NLR ≥3 in the blood or NLR ≥3 in the tumor biopsies or a percentage of MDSCs ≥ 30% in the tumour biopsies PS (ECOG scale) 0-1 Adequate hepatic function: ALT and ASAT ≤ 2.5 x ULN, Bilirubin ≤ 1.5 ULN (exception if Gilbert's syndrome ≤ 2.5 x ULN) Adequate renal function: calculated creatinine clearance ≥ 50 ml/min according to the formula of Cockcroft-Gault Hemoglobin ≥ 10 g/dl, leukocyte count ≥ 4.0 x 103/µl, platelet count ≥ 200 x 103/µl Informed Consent as documented by the patient's signature Exclusion Criteria: No history of coagulation disorders and normal INR Significant cardiovascular disorders in the last 12 months Other clinically significant concomitant disease states which in the opinion of the Investigator may represent contraindications to study participation Known or suspected non-compliance Participation in another study with investigational drug within the 30 days preceding and during the present study Ongoing treatment with strong CYP3A4 inhibitors or dual CYP2C9 and CYP3A4 inhibitors

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruxolitinib<br>Oral administration of Ruxolitinib 20mg BID for 28 consecutive days | Drug: Ruxolitinib 20 MG<br>* tablets<br>* Other names: Jakavi;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor immune response | Tumor immune response modification induced by Ruxolitinib | 9 wks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pSTAT3 | Decrease of pSTAT3 | 5 wks | 
| Cytokines | Reduction of cytokines associated to myeloid cells recruitment and tumor-promoting factors (e.g. IL8, IL6, TGF) | 6 wks | 
| KI-67 | Reduction by 50% of KI-67 | 9 wks | 
| biomarkers | Increase of senescence and apoptosis markers (p16, p21, Beta-galactosidase, Caspase-3, Caspase-8) | 5 wks |