Whole Body Magnetic Resonance Imaging Study (WISE)

In prostate cancer bone is the most common site for cancer spread, causing pain, fractures, nerve compression and death.

New therapies are available for treating bone disease from cancer and this means that by maintaining patients on drugs that are effective and switching patients to other drugs when current treatment becomes ineffective, patients can be maintained 'better for longer'. However, to do this, it is necessary to accurately tell whether a given treatment is working or not.

In this study, the investigators will perform whole body MRI scans, which include a special scan called diffusion-weighted MRI (DWI MRI) that can provide more information about the participants extent of disease. The investigators aim to show that this test is better than the standard tests of CT and bone scan currently used in the NHS to monitor bone disease. The information from this study will be used to test a special software so that the test may more widely benefit patients across the NHS in the future.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Prostate Cancer
• Intervention / Treatment: Diagnostic test: WB-MRI

Detailed Description

In patients with prostate cancer the current methods to assess treatment response of bone disease such as computer tomography (CT) and bone scan (BS)are unreliable, insensitive to bone disease and have limited criteria to assess disease response confined to bones. Blood tests are inaccurate although some newer tests (e.g. circulating tumour cells tests) show promise but are still under investigation and nuclear medicine investigations such as PET/CT imaging have higher sensitivity, meaning they can detect more sites of disease who are indeed disease than CT or BS but they are more costly and less widely available compared with MRI within the NHS.

For this study the Whole body MRI (WB-MRI) includes a measurement called diffusion-weighted imaging (DWI) which is relatively new and has a high sensitivity for bone metastases. This technique can be used to measure total bone disease volume (TDV) and the disease apparent diffusion coefficient (ADC) which reflects the tumour tissue cell density. Previous studies have shown good reproducibility of both these measurements and a significant increase in the mean tumour ADC is observed in patients who are responding to effective treatment.

However WB-MRI application across the NHS is ad-hoc, CT and BS techniques are entrenched within clinical practice despite their known limitations. Another factor that limits wider adoption of WB-MRI is the lack of sophisticated analysis software to enable disease across the body to be quickly evaluated.

This multi-centre imaging study will provide the opportunity to evaluate the performance of WB-MRI with a novel software diagnostics for evaluating the treatment response of advanced prostate cancer patients.

This prototype can used to evaluate WB-MRI data from different scanners and address a current major unmet need for the treatment and follow-up of patients with bone disease from cancers, so that the test may more widely benefit patients across the NHS in the future.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

Study Locations

• United Kingdom
  • Surrey
    • Sutton, Surrey, United Kingdom, SM2 5PT
      • The Royal Marsden NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Non-Probability Sample

Study Population

Advanced prostate cancer patients with bone predominant metastases and no RECIST-measurable disease (lymph nodes <1.5cm in short axis in the pelvis are allowed) who have an indication for systemic treatment (taxane chemotherapy or AR targeted agents).

Description

Inclusion Criteria:

1. Written informed consent
2. Age ≥18 years
3. Patients with APC with predominantly bone disease confirmed by bone scan (within 6 weeks) or CT (within 6 weeks), of starting treatment (Cycle 1 Day 1). Patients with local recurrence and bone metastases with an associated soft tissue component, will be allowed into the trial. Pelvic lymphadenopathy <1.5cm in short axis is not an exclusion.
4. Systemic therapy indicated for disease progression, as clinically indicated.

Exclusion Criteria:

1. Patient is claustrophobic.
2. Contraindications to MRI examination (e.g. cardiac pacemakers, cochlear implants).
3. Measurable soft tissue or lymph node metastases or any metastatic disease outside the bone that is RECIST measurable will be an exclusion (unless it is pelvic nodal disease <1.5cm in short axis). Bone metastases with associated soft tissue components will also not be an exclusion.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic performance of WB MRI at post treatment by quantification of bone disease	To establish the diagnostic performance of whole body MRI (WB MRI) using total bone disease volume (TDV) and disease apparent diffusion coefficient (ADC) at Cycle 3 (within 2 weeks before treatment on C4 Day1, each cycle being 28 days or 21 days depending on the type of standard therapy) using new software diagnostics for assessing treatment response to standard therapy (taxane chemotherapy or AR targeted agents)) in patients with bone predominant metastatic disease in prostate cancer using a construct reference standard.	End of Cycle 3 of treatment (each cycle being 28 days or 21 days depending on the type of standard therapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare diagnostic performance of WB-MRI at Cycle 3 versus standard imaging CT and bone scan by quantification of bone disease	Compare the diagnostic performance of WB-MRI using TDV and ADC at Cycle 3 (within 2 weeks before treatment on C4 Day1, each cycle being 28 or 21 days depending on the type of standard therapy) with the diagnostic performance of standard imaging CT and BS (when available).	End of Cycle 3 of treatment (each cycle being 28 days or 21 days depending on the type of standard therapy)
Time to progression of responders and non-responders	Determine the time to progression of responders and non-responders to therapy as defined by WB MRI, versus CT and BS.	6 months
Intra-observer and inter-observer agreement of ADC and TDV	Assess the intra-observer and inter-observer agreement of the apparent diffusion coefficient (ADC) and total diffusion volume (TDV) of bone disease assessed by WB-MRI.	1 year
Assess the cost-effectiveness of replacing CT and BS with WB-MRI derived measurements TDV and ADC	Determine the cost-effectiveness of replacing CT and BS with WB-MRI derived TDV and ADC measurements for disease management in patients with prostate bone disease using QALYs.	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histogram parameters of ADC	Explore histogram parameters of ADC in responders and non-responders to treatment.	6 months
Histogram parameters of TDV	Explore histogram parameters of TDV in responders and non-responders to treatment.	6 months
Histogram parameters of fat fractions	Explore histogram parameters of fat fractions in responders and non-responders to treatment.	6 months
Cost and cost-effectiveness to the NHS of replacing the standard practice conventional tests	Assess the cost and cost-effectiveness to the NHS of replacing the standard practice conventional tests CT and BS with WB-MRI-derived TDV and ADC measurements for disease management in patients with prostate bone disease using the advanced computer diagnostics software in development using QALYs and obtained from survival data and health-related quality of life.	1 year

Collaborators and Investigators

• Sponsor: Royal Marsden NHS Foundation Trust
• Collaborators: Institute of Cancer Research, United Kingdom; National Institute for Health Research, United Kingdom

Study record dates

Study Major Dates

• Study Start (Actual): October 9, 2019
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): June 1, 2021

Study Registration Dates

• First Submitted: September 26, 2019
• First Submitted That Met QC Criteria: October 4, 2019
• First Posted (Actual): October 7, 2019

Study Record Updates

• Last Update Posted (Actual): May 19, 2021
• Last Update Submitted That Met QC Criteria: May 18, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Prostate cancer; Bone disease; WB-MRI
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms
• Other Study ID Numbers: CCR 5035

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Fully anonymised trial data will be made available
• IPD Sharing Time Frame: Data will be available within 1 year of study completion.
• IPD Sharing Supporting Information Type: CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No