Whole-Body Diffusion-Weighted Magnetic Resonance Imaging (MRI) as a Response Biomarker for Metastatic Prostate Cancer

Study Overview
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Brief Summary
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The skeleton is the most frequent organ of distal metastases in prostate cancer, often representing the only site of metastatic disease. Still, assessment of response and progression to therapies in bone metastases remains a major unmet need, to aid treatment switch decisions, detecting primary/secondary resistance and to optimize drug development. The currently used standard imaging techniques, computed tomography (CT) and bone scintigraphy (BS), do not depict the true extent of bone metastases and are suboptimal in capturing biological changes occurring in response to treatment. This results in treatment switch decisions too often being based on PSA changes, which is neither a surrogate of survival, nor an optimal response biomarker.Diffusion-weighted imaging (DWI) is a functional magnetic resonance imaging (MRI) technique that studies the movement of water molecules within a tissue and provides valuable information about the tissue microstructure and cellularity. Whole body MRI with DWI is highly accurate for bone metastases detection, outperforming the standard CT and BS and other imaging techniques when assessing bone metastases. The investigators hypothesise that DWI changes are a response biomarker in bone metastases from metastatic castration resistant prostate cancer (mCRPC); these DWI changes can be detected as early as after 4 weeks of systemic treatment.

Official Title
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A Study to Clinically Qualify Whole-Body Diffusion-Weighted Magnetic Resonance Imaging (MRI) in Patients With Metastatic Castration Resistant Prostate Carcinoma With Bone Metastases

Conditions
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Prostate Cancer Metastatic

Intervention / Treatment
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* Diagnostic Test: Whole-Body Diffusion Weighted MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men 18 or over years old. Patients with castration resistant prostate cancer. Evidence of bone metastases by any imaging technique. Patients due to start treatment with abiraterone or enzalutamide. In the exploratory cohorts, we will include patients due to start treatment with other systemic therapies for advanced prostate cancer (A-taxanes, B-radiopharmaceuticals, C-other therapies). Written (signed and dated) informed consent. Exclusion Criteria: Contraindications to MRI. Inability of patient to tolerate whole body MRI (e.g. claustrophobia). Patients who have received radiotherapy within the last three months and with no bone metastases outside the radiotherapy field.

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: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Metastatic prostate cancer<br>Patients will receive whole-body MRI with diffusion-weighted imaging at baseline and after 4 and 8 weeks of treatment. | Diagnostic Test: Whole-Body Diffusion Weighted MRI<br>* MRI at baseline, after four and eight weeks of treatment and at disease progression or treatment discontinuation.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in diffusion-weighted MRI as response biomarker | Apparent Diffusion Coefficient (ADC) percentage change in responders vs non-responders to systemic treatment in patients with CRPC and bone metastases | 8 weeks after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early response biomarker identification | Apparent Diffusion Coefficient (ADC) percentage change in responders vs non-responders to systemic treatment in patients with CRPC and bone metastases | 4 weeks after treatment | 
| Intra-tumor heterogenous response evaluation | To use diffusion-weighted MRI for identifying anatomic regions of subclonal resistance to systemic treatment and study tumour evolution. | 4 and 8 weeks after treatment and at disease progression by standard criteria, on average 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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response biomarker, functional imaging, MRI