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Effect of Ruxolitinib on Tumor Infiltrating Myeloid Cells

Primary Purpose

Prostate Cancer

Status

Withdrawn

Phase

Not Applicable

Locations

Switzerland

Study Type

Interventional

Intervention

Ruxolitinib 20 MG

About this trial

This is an interventional treatment trial for Prostate Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

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

Sites / Locations

Istituto Oncologico della Svizzera Italiana (IOSI)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Ruxolitinib

Arm Description

Oral administration of Ruxolitinib 20mg BID for 28 consecutive days

Outcomes

Primary Outcome Measures

Tumor immune response

Tumor immune response modification induced by Ruxolitinib

Secondary Outcome Measures

pSTAT3

Decrease of pSTAT3

Cytokines

Reduction of cytokines associated to myeloid cells recruitment and tumor-promoting factors (e.g. IL8, IL6, TGF)

KI-67

Reduction by 50% of KI-67

biomarkers

Increase of senescence and apoptosis markers (p16, p21, Beta-galactosidase, Caspase-3, Caspase-8)

Full Information

NCT ID

NCT03274778

First Posted

September 5, 2017

Last Updated

March 24, 2020

Sponsor

Oncology Institute of Southern Switzerland

1. Study Identification

Unique Protocol Identification Number

NCT03274778

Brief Title

Effect of Ruxolitinib on Tumor Infiltrating Myeloid Cells

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Withdrawn

Why Stopped

Recruitment difficulty due to eligibility criteria.

Study Start Date

September 1, 2017 (Actual)

Primary Completion Date

March 24, 2020 (Actual)

Study Completion Date

March 24, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Oncology Institute of Southern Switzerland

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Prostate Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Ruxolitinib

Arm Type

Experimental

Arm Description

Oral administration of Ruxolitinib 20mg BID for 28 consecutive days

Intervention Type

Drug

Intervention Name(s)

Ruxolitinib 20 MG

Other Intervention Name(s)

Jakavi

Intervention Description

tablets

Primary Outcome Measure Information:

Title

Tumor immune response

Description

Tumor immune response modification induced by Ruxolitinib

Time Frame

9 wks

Secondary Outcome Measure Information:

Title

pSTAT3

Description

Decrease of pSTAT3

Time Frame

5 wks

Title

Cytokines

Description

Reduction of cytokines associated to myeloid cells recruitment and tumor-promoting factors (e.g. IL8, IL6, TGF)

Time Frame

6 wks

Title

KI-67

Description

Reduction by 50% of KI-67

Time Frame

9 wks

Title

biomarkers

Description

Increase of senescence and apoptosis markers (p16, p21, Beta-galactosidase, Caspase-3, Caspase-8)

Time Frame

5 wks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andrea Alimonti, Prof.

Organizational Affiliation

Institute of Oncology Research (IOR)

Official's Role

Study Director

Facility Information:

Facility Name

Istituto Oncologico della Svizzera Italiana (IOSI)

City

Bellinzona

ZIP/Postal Code

6500

Country

Switzerland

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Effect of Ruxolitinib on Tumor Infiltrating Myeloid Cells

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