Imperial Prostate 7 - Prostate Assessment Using Comparative Interventions - Fast Mri and Image-fusion for Cancer (IP7-PACIFIC)

• ClinicalTrials.gov Identifier: NCT05574647
• Recruitment Status: Not yet recruiting
• First Posted: October 10, 2022
• Last Update Posted: October 10, 2022
• Sponsor: Imperial College London
• Collaborators: Cancer Research UK; National Institute for Health Research, United Kingdom
• Information provided by (Responsible Party): Imperial College London

Study Description

Brief Summary:

To evaluate the role of biparametric MRI and image-fusion targeted biopsies for the detection of prostate cancer.

To determine whether biparametric MRI (bpMRI) could be recommended as an alternative to multiparametric MRI (mpMRI) for the detection of clinically significant prostate cancers in patients at risk.

To determine whether image-fusion targeted biopsy is better than visual-registration (cognitive) targeted biopsy at detecting clinically significant prostate cancers in patients requiring prostate biopsy due to a suspicious MRI.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer; Adenocarcinoma; Prostatic Neoplasms; Prostatic Diseases; Neoplasms	Diagnostic Test: bpMRI; Diagnostic Test: Image-Fusion targeted and systematic Biopsy	Not Applicable

Detailed Description:

Background and study aims:

The aim of this study is to improve the way prostate cancer is diagnosed by looking at two different types of MRI scans and two different types of prostate biopsy (tissue samples). A large study such as this is required to help the NHS decide how to diagnose prostate cancer in the future. If a person is suspected of having prostate cancer, then they are referred by their GP. At the hospital clinic, the participant will then have an MRI scan. If this scan shows that cancer might be present, then the doctor will usually suggest that the patient has a biopsy. There are two ways of doing a prostate MRI. One takes 30-40 minutes and requires a contrast injection called gadolinium (like a dye). This is called long MRI and is most commonly used in the NHS. Gadolinium is safe as it rarely causes any bad reaction but using it means that the scan takes more time. Another type of MRI takes 15-20 minutes and does not use gadolinium contrast. This is called a short MRI. Many studies over the last 5 years have shown that the long and short MRIs are similar in their accuracy in diagnosing important prostate cancer. These studies have not been of high quality or large enough to change NHS practice. Patients with suspicious areas on the MRI are usually advised to have a prostate biopsy. This involves taking tissue samples using a needle. The samples are then looked at under the microscope by a pathologist to see if cancer cells are present. There are two ways of doing a prostate biopsy. One is where the person doing the biopsy decides where to put the biopsy needle by looking at the MRI scans that have been already taken on a computer screen. The needle is guided to the prostate using live ultrasound scans that are shown on a different screen near the patient. The biopsy operator makes a judgement about where to place the biopsy needles. This is called visual registration. Tissue samples from other areas of the prostate that look normal on the MRI scans are also taken to ensure cancer is not missed. The other type of biopsy is called image fusion. During image fusion biopsy, the biopsy operator uses the MRI scans that have been taken beforehand but laid on top of the live ultrasound images during the biopsy. This uses software and takes a few minutes longer to perform. Once the MRI images and ultrasound images are 'fused', the actual biopsies are taken as normal. Studies over the last 5 years have shown mixed results. Some have shown that image fusion biopsy is no better than visual registration biopsy, whilst a few have shown it might make a difference in improving cancer detection. As a result, it is not known for certain which way is better. A large study is needed to show whether the investigators need to do image fusion or not, in order for the NHS to decide whether or not to use it in all hospitals doing prostate biopsies.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 3600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: two linked RCTs which will test whether bpMRI and image-fusion make a difference if used in clinical practice, across multiple centres, without the incorporation bias inherent in paired-cohort studies
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Evaluating the Role of Biparametric MRI and Image-fusion Targeted Biopsies for Detection of Prostate Cancer
• Estimated Study Start Date: October 1, 2022
• Estimated Primary Completion Date: October 31, 2025
• Estimated Study Completion Date: January 31, 2026

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Standard: mpMRI; Participants will undergo mpMRI. Blinding will not be possible. Once the MRI report is issued, the local clinical team will make a decision about advising whether a biopsy is necessary or not.
Active Comparator: Intervention 1: bpMRI; Participants will undergo bpMRI. Blinding will not be possible. Once the MRI report is issued, the local clinical team will make a decision about advising whether a biopsy is necessary or not.	Diagnostic Test: bpMRI; biparametric MRI takes 30-40 minutes and requires a contrast injection called gadolinium (like a dye). This is also called long MRI and is most commonly used in the NHS.; Other Name: biparametric MRI
No Intervention: Standard: Visual estimation targeted and systematic biopsy; Randomisation 2 will only be relevant if participants are advised by their clinical team to have a biopsy based on their MRI and other clinical factors. Participants advised to have a biopsy will undergo a visual estimation targeted biopsy
Active Comparator: Intervention 2: Image-fusion targeted and systematic biopsy; Randomisation 2 will only be relevant if participants are advised by their clinical team to have a biopsy based on their MRI and other clinical factors. Participants advised to have a biopsy will undergo an image fusion targeted biopsy.	Diagnostic Test: Image-Fusion targeted and systematic Biopsy; During image fusion targeted biopsy, the biopsy operator uses the MRI scans that were taken beforehand but laid on top of the live ultrasound images during the biopsy. This uses software and takes a few minutes longer to perform. Once the MRI images and ultrasound images are 'fused', the actual biopsies are taken as normal.

Outcome Measures

Primary Outcome Measures :

1. Randomisation 1: Proportion of clinically significant cancers detected in the randomised population of patients at risk. [ Time Frame: maximum 12 weeks following enrolment ]
   Proportion of clinically significant cancers, defined as any amount of Gleason ≥3+4 (ISUP Grade Group ≥2) on biopsy, detected in the randomised population of patients at risk.
2. Randomisation 2: Proportion of clinically significant cancers detected in the randomised population of patients biopsied for a suspicious MRI. [ Time Frame: maximum 12 weeks following enrolment ]
   Proportion of clinically significant cancers, defined as any amount of Gleason ≥3+4 (ISUP Grade Group ≥2) on biopsy, detected in the randomised population of patients biopsied for a suspicious MRI.

Secondary Outcome Measures :

1. MRI related adverse events [ Time Frame: maximum 12 weeks following enrolment ]
   MRI related adverse events measured using documentation
2. MRI related serious adverse events [ Time Frame: maximum 12 weeks following enrolment ]
   MRI related serious adverse events measured using documentation
3. Biopsy related adverse events [ Time Frame: maximum 12 weeks following enrolment ]
   biopsy-related adverse events measured using documentation
4. Biopsy related serious adverse events [ Time Frame: maximum 12 weeks following enrolment ]
   biopsy-related serious adverse events measured using documentation
5. The proportion of patients advised to undergo a needle biopsy after MRI [ Time Frame: maximum 12 weeks following enrolment ]
   The proportion of patients advised to undergo a needle biopsy. The researchers will document common reasons for patients who are advised to undergo a biopsy or advised against a needle biopsy and still choose to have a biopsy.
6. The proportion of patients advised to undergo a prostrate biopsy after MRI [ Time Frame: maximum 12 weeks following enrolment ]
   The proportion of patients undergoing a prostate biopsy after MRI. The researchers will document common reasons for patients who are advised to undergo prostrate biopsy after MRI.
7. The proportion of patients diagnosed with clinically significant prostates cancers on needle biopsy [ Time Frame: maximum 12 weeks following enrolment ]
   The proportion of patients diagnosed with clinically significant prostates cancers defined as any Gleason 3+3=6 on needle biopsy carried out after MRI.
8. The proportion of patients diagnosed with clinically significant prostate cancers on prostate biopsy carried out after MRI [ Time Frame: maximum 12 weeks following enrolment ]

   The proportion of patients diagnosed with clinically significant prostate cancers using other histological thresholds on prostate biopsy carried out after MRI.

   The researchers will evaluate these proportions by MRI score at patient and lesion level (on a scale of 1 to 5) and by the presence or absence of clinical risk parameters.

9. The proportion of patients diagnosed with clinically significant prostate cancers with targeted biopsy using four targeted cores [ Time Frame: maximum 12 weeks following enrolment ]
   The proportion of patients diagnosed with clinically significant prostate cancers using all histological thresholds on targeted biopsy using four targeted cores
10. The proportion of patients diagnosed with clinically significant prostate cancers with targeted biopsy using six targeted cores [ Time Frame: maximum 12 weeks following enrolment ]
    The proportion of patients diagnosed with clinically significant prostate cancers using all histological thresholds on targeted biopsy using six targeted cores
11. Detection rates for each randomised group of known prognostic risk categories [ Time Frame: maximum 12 weeks following enrolment ]
    Detection rates for each randomised group of known prognostic risk categories. These are D' Amico, National Comprehensive Cancer Network (NCCN) and Cambridge Prognostic Groups (CPG).
12. Use Likert MRI scoring system to analyse the proportion of patients biopsied [ Time Frame: maximum 12 weeks following enrolment ]
    A comparison of the two MRI scoring systems, Likert and PIRADS (the latest version as defined in MRI Reporting SOP), in terms of the proportion of patients biopsied and subsequently diagnosed with clinically significant and clinically insignificant prostate cancer, using each of the histological thresholds, on a prostate biopsy.
13. Use Prostate Imaging Reporting and Data System (PIRADS) MRI scoring system to analyse the proportion of patients biopsied [ Time Frame: maximum 12 weeks following enrolment ]
    A comparison of the two MRI scoring systems, Likert and PIRADS (the latest version as defined in MRI Reporting SOP), in terms of the proportion of patients biopsied and subsequently diagnosed with clinically significant and clinically insignificant prostate cancer, using each of the histological thresholds, on a prostate biopsy.
14. Characteristics of cancer in targeted systematic biopsies [ Time Frame: maximum 12 weeks following enrolment ]
    Characteristics of cancer in targeted versus systematic biopsies by MRI score, PSA, PSA density, age, ethnicity, family history and history of prior prostate biopsy with a multivariable evaluation to determine whether patients might avoid systematic sampling in the future.
15. Characteristics of cancer in targeted biopsies [ Time Frame: maximum 12 weeks following enrolment ]
    Characteristics of cancer in targeted versus systematic biopsies by MRI score, PSA, PSA density, age, ethnicity, family history and history of prior prostate biopsy with a multivariable evaluation to determine whether patients might avoid systematic sampling in the future.
16. External validation of the Imperial Rapid Access to Prostate Imaging and Diagnosis (RAPID) Risk Score (MRI+) [ Time Frame: maximum 12 weeks following enrolment ]
    External validation of the Imperial RAPID Risk Score (MRI+) within each randomised group of the IP7-PACIFIC study, external validation
17. External validation of the Imperial Rapid Access to Prostate Imaging and Diagnosis (RAPID) Risk Score in (Systematic+) [ Time Frame: maximum 12 weeks following enrolment ]
    External validation of Imperial Rapid Access to Prostate Imaging and Diagnosis(RAPID) Risk Score (Systematic+) within each randomised group of the IP7-PACIFIC study, external validation
18. Impact of prostate biopsy in first randomised group (bpMRI) on patient-reported outcomes [ Time Frame: maximum 12 weeks following enrolment ]
    Impact of prostate biopsy in each randomised group on patient-reported outcomes using a survey that includes EQ-5D-5L health-related quality of life questionnaire
19. Impact of prostate biopsy in second randomised group (mpMRI)on patient-reported outcomes [ Time Frame: maximum 12 weeks following enrolment ]
    Impact of prostate biopsy in each randomised group on patient-reported outcomes using a survey that includes EQ-5D-5L health-related quality of life questionnaire
20. Impact of prostate biopsy in first randomised group (bpMRI) on patient-reported experience measures [ Time Frame: maximum 12 weeks following enrolment ]
    Impact of prostate biopsy in each randomised group on patient-reported experience measures using version of the Prospective cohort study (Prostate Biopsy Effects: ProBE) questionnaire.
21. Impact of prostate biopsy in second randomised group (mpMRI) on patient-reported experience measures [ Time Frame: maximum 12 weeks following enrolment ]
    Impact of prostate biopsy in each randomised group on patient-reported experience measures using version of the Prospective cohort study (Prostate Biopsy Effects: ProBE) questionnaire.
22. Analysis of biopsy rate in cancer detection (by all histological thresholds) during the time of study [ Time Frame: maximum 12 weeks following enrolment ]

    Analysis of biopsy rates in cancer detection (by all histological thresholds) in the randomised group will be conducted by centre using centre size.

    MRI scanner type (1.5 Tesla vs. 3.0 Tesla), type of biopsy route used (transrectal vs trans perineal), number of systematic biopsies taken (limited systematic vs extended systematic biopsy), type of analgesia/anaesthetic (local anaesthetic, sedation or general anaesthetic) as additional stratification factors

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Patients with a prostate (either cis-male gender or trans-female gender with no prior androgen deprivation hormone use at all)
• Accepts Healthy Volunteers: No

Criteria

Randomisation 1

Inclusion Criteria:

• Age 18 years or above (no upper limit)
• Patients with a prostate (either cis-male gender or trans-female gender with no prior androgen deprivation hormone use at all).
• Referred to hospital and advised to undergo a prostate MRI because of an abnormal digital rectal examination (regardless of PSA level) and/or an elevated PSA (within 6 months of screening visit) PSA >/=3.0ng/ml for age 50-69 years PSA >/=5.0ng/ml for age >/=70 years If family or ethnic risk for prostate cancer, PSA >/=2.5ng/ml for age 45-49 years

Exclusion Criteria:

• PSA >50ng/ml
• Prior prostate MRI or prostate biopsy in the two years prior to screening visit
• Prior diagnosis of prostate cancer
• Contraindication to MRI or gadolinium contrast
• Previous hip replacement to both hips
• Contraindication to performing a biopsy guided by a transrectal ultrasound probe

Randomisation 2

Inclusion Criteria:

• Visible suspicious finding on mpMRI or bpMRI from randomisation 1 requiring a targeted biopsy (MRI score 3, 4, 5 on either Likert or PIRADS schema)

Exclusion Criteria:

• As above for randomisation 1
• Patient refusal for biopsy

Contacts and Locations

Contacts

Contact: Hashim Ahmed; 0203 311 1673; hashim.ahmed@imperial.ac.uk

Contact: Thiagarajah Sasikaran; 0207 594 6017; t.sasikaran@imperial.ac.uk

Sponsors and Collaborators

Imperial College London

Cancer Research UK

National Institute for Health Research, United Kingdom

More Information

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT05574647
• Other Study ID Numbers: 22CX7488
• First Posted: October 10, 2022
• Last Update Posted: October 10, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Imperial College London:

Prostate Cancer; Prostate-Specific Antigen; bpMRI; mpMRI; Prostate biopsy; Multi-parametric MRI; Biparametric MRI

Additional relevant MeSH terms:

Prostatic Neoplasms; Neoplasms; Prostatic Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases