Effect of Ruxolitinib on Tumor Infiltrating Myeloid Cells

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

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.

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.

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