Windows Trial of INsulin-like Growth Factor Neutralising Antibody Xentuzumab in MEN Scheduled for Radical Prostatectomy (WINGMEN)

Study Overview
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Brief Summary
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The WINGMEN trial aims to understand how a hormone-like protein called insulin-like growth factor (IGF) helps prostate cancers grow and become aggressive. IGF is required for normal development, and also helps cancers grow and spread. Men with high blood IGF are at increased risk of developing prostate cancer, and tall men are more likely to get aggressive prostate cancer. The WINGMEN trial will recruit 30 men with prostate cancer who have been offered an operation to remove the prostate. Most men have to wait 4-5 weeks between a decision to have prostate removal surgery, and actually having the operation. In this 4-5 week window we will offer treatment with a new IGF-blocker drug called xentuzumab. The drug is provided by Boehringer Ingelheim and the trial is funded by Prostate Cancer UK. Xentuzumab will be given as an outpatient by once weekly intravenous infusion (drip) in the Early Phase Clinical Trials Unit, Oxford Cancer Centre, Churchill Hospital. In other trials, xentuzumab is being tested in patients with advanced cancer, and is proving to be well-tolerated. After the 4-week treatment, WINGMEN trial patients will have routine prostate removal surgery. Samples of blood and prostate cancer that are surplus to diagnostic need will be taken from the diagnostic prostate biopsy (pre-xentuzumab) and the cancer removed at surgery (after xentuzumab) for research tests. These samples will be compared to measure how effectively xentuzumab reduces signs of tumour growth, and identify which genes and proteins are switched on or off by xentuzumab, and which may therefore be important in helping IGF promote prostate cancer growth. The information we get from the WINGMEN trial may help us to improve treatment of men with prostate cancer, with the long-term aim of reducing the risk of aggressive prostate cancer

Official Title
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Windows Trial of INsulin-like Growth Factor Neutralising Antibody Xentuzumab in MEN Scheduled for Radical Prostatectomy (WINGMEN)

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Xentuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A patient will be eligible for inclusion in this study if all of the following criteria apply. Men with prostate adenocarcinoma confirmed on prostate biopsy and with sufficient cancer-containing biopsy tissue surplus to diagnostic need to provide 2 sections for primary endpoint analysis. Scheduled for open or robotic radical prostatectomy Age ≥ 18 years Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 (Appendix 1) The patient is willing and able to comply with the protocol scheduled follow-up visits and examinations for the duration of the study Participant is willing and able to give informed consent. Participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the trial and for 70 days thereafter. Adequate hematologic, renal and hepatic function, defined as follows: Laboratory Test Value required Hemoglobin (Hb) ≥90g/L White Blood Count (WBC) >2.5 x 10*9/L Absolute Neutrophil Count (ANC) ≥ 1.5 x10*9/L Platelet count ≥ 100 x 10*9/L AST, ALT, and alkaline phosphatase ≤ 2.5 x upper limit of normal eGFR* ≥30ml/min *eGFR calculated by Cockcroft & Gault formula, Exclusion Criteria: A patient will not be eligible for the trial if any of the following apply: Treated with systemic corticosteroids, insulin, metformin, other oral hypoglycemic agent, or anti-androgens in the 28 days prior to first dose of study drug Diabetes mellitus Previous prostate radiotherapy Current or previous treatment with xentuzumab or other IGF or GH -modifying therapy Patients who are known to be serologically positive for Hepatitis B, Hepatitis C or HIV Treatment with any other investigational agent, or treatment in another interventional clinical trial within 28 days prior to enrolment Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: This is a phase 0 'window of opportunity' study testing whether xentuzumab blocks IGF signalling and markers of growth in men with localised prostate cancer scheduled for radical prostatectomy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xentuzumab<br>All patients will be allocated to receive Xentuzumab | Drug: Xentuzumab<br>* The study IMP is xentuzumab, a humanised IgG1 monoclonal antibody that neutralises the IGF ligands to inhibit activation of IGF-1R and INSR-A, suppressing IGF-mediated proliferation, invasion and therapy resistance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the amount of IGF pathway blockade induced by xentuzumab | Phospho-IGF-1R and phospho-AKT (or downstream target) immunohistochemistry | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess feasibility of treatment in the pre-prostatectomy setting | Number of patients whose radical prostatectomy is performed on schedule after 4 doses of xentuzumab. | Up to 24 weeks | 
| Incidence of Treatment-Emergent Adverse Events | Treatment-related adverse events scored using CTCAE v4.03 | Up to 24 weeks |