PSMA PET Additive Value for Prostate Cancer Diagnosis in Men With Negative/Equivocal MRI (PRIMARY2)

• ClinicalTrials.gov Identifier: NCT05154162
• Recruitment Status: Recruiting
• First Posted: December 10, 2021
• Last Update Posted: July 28, 2023
• Sponsor: Peter MacCallum Cancer Centre, Australia
• Collaborator: St Vincent's Hospital, Sydney
• Information provided by (Responsible Party): Peter MacCallum Cancer Centre, Australia

Tracking Information

• First Submitted Date: October 25, 2021
• First Posted Date: December 10, 2021
• Last Update Posted Date: July 28, 2023
• Actual Study Start Date: March 2, 2022
• Estimated Primary Completion Date: March 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2021)

• Presence of sPCa on prostate biopsy [ Time Frame: When histology results are available, at an expected average of 14 days post-biopsy ]
  sPCa defined as Gleason score 3+4(>10%)=7, Grade group 2 Patients without biopsy (negative PSMA PET) are considered not to have sPCa.
• Number of men who avoid transperineal prostate biopsy in the experimental arm [ Time Frame: When the PSMA PET result is available, at most 28 days after randomisation ]
  In the experimental arm, if PSMA PET is negative, the patient does not have biopsy

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 30, 2021)

• Presence of insignificant prostate cancer (isPCa) on prostate biopsy [ Time Frame: Within 3 months following randomisation ]
  isPCa defined as GS 3+3=6, GG 1 or GS 3+4(≤10%)=7, GG 2
• Cost per quality adjusted life year [ Time Frame: Through study completion, estimated up to 2 years ]
  cost-effectiveness analysis to assess the cost per quality adjusted life year (QALY) gained associated with the use of PSMA PET in addition to MRI compared with MRI alone for the diagnosis of sPCa. Importantly, this analysis will take into consideration the impact on costs and QoL associated with the hypothesised reduction in unnecessary biopsies arising from the improved accuracy of PSMA+MRI and the comparative interventions).
• Health-related quality of life as measured by the EORTC QLQ-C30. [ Time Frame: Within 7 days of randomisation and every 6 months ± 30 days after randomisation ]
  Quality of life (QoL) will be assessed using QLQ-C30, which contains 30 items across five functional scales, three symptom scales, global health status, and six single items. Participant responses are collected using a four-point response scale ranging from 'Not at all' to "Very much". Higher scores indicate better QoL and function, while high scores for the symptom scale represent a high level of symptoms.
• Anxiety as measured by the GAD7 in the diagnosis of PCa. [ Time Frame: Within 7 days following randomisation and every 6 months ± 30 days after randomisation ]
  The generalized anxiety disorder Scale (GAD-7)14 is a 7-item, patient-rated questionnaire for screening and severity measuring of generalised anxiety disorder. The GAD-7 score is calculated by assigning scores of 0, 1, 2, and 3, to the response categories of 'not at all', 'several days', 'more than half the days', and 'nearly every day', respectively, and adding together the scores for the seven questions. Scores of 5, 10, and 15 are taken as the cut-off points for mild, moderate and severe anxiety, respectively.
• Cancer worry in the diagnosis of PCa. [ Time Frame: Within 7 days following randomisation and every 6 months ± 30 days after randomisation ]
  The modified Cancer Worry Scale adaptation of Cancer Worry Scale is a 3-item questionnaire used in context of cancer worry in abnormal PSA levels in men participating in community screening program. The score is calculated by assigning scores of 1, 2, 3, and 4, to the categories 'not at all or rarely', 'sometimes', 'often', and 'a lot', respectively, and adding together the scores for the 3 questions. A final question asks about feelings of distress related to cancer risk.
• Number of biopsy cores [ Time Frame: Within 3 months following randomisation ]
  Experimental arm: For patients with a positive PSMA PET, the images, the report and a simplified template will be made available to the treating urologist. Up to four identified lesions on PSMA PET and/or MRI will be targeted with each lesion having a minimum 5 cores. Control arm: Transperineal template prostate biopsies will be performed as per treating urologist's usual practice. No specific template for biopsy is prescribed for the purposes of the study. However, template sampling of the prostate is required, with a minimum of 12 cores,dependent on prostate volume.
• Incidence of complications following transperineal prostate biopsy. [ Time Frame: Within 7 days following randomisation and at 3 and 6 months after randomisation ]
  Complications following biopsy will be assessed with a modified questionnaire validated in the PRECISION trial. Part 1 following randomisation is a 9 item questionnaire. Part 2 is a 23 item questionnaire administered at 3 and 6 months to assess complications from transperineal prostate biopsy. The following complications will be assessed via these forms: fever, blood in urine, blood in semen, blood in stool, acute urinary retention, erectile dysfunction, urinary incontinence, urinary tract infection and pain in the perineum.
• Incidence of erectile dysfunction following transperineal prostate biopsy [ Time Frame: Within 7 days following randomisation and at 3 and 6 months after randomisation ]
  The Sexual Health Inventory for Men (SHIM) is an adapted version of the 5 item International Index of Erectile Function (IIEF-5) score, developed to diagnose the presence and severity of erectile dysfunction. This validated questionnaire has a range of scores from 1 to 25, grading erectile dysfunction into 5 categories (none, mild, mild to moderate, moderate and severe).
• Number of men who have sPCa detected only with PSMA PET (MRI PI-RADS 2) [ Time Frame: Within 28 days following randomisation ]
  Measured in the experimental arm in patients with positive PSMA PET and negative MRI (PIRADS 2). sPCa defined as Gleason score 3+4(>10%)=7, Grade group 2

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: PSMA PET Additive Value for Prostate Cancer Diagnosis in Men With Negative/Equivocal MRI
• Official Title: Prospective Multi-centre Randomised Trial of the Additive Diagnostic Value of PSMA PET in Men With Negative/Equivocal MRI in the Diagnosis of Significant Prostate Cancer
• Brief Summary: This clinical trial will evaluate PSMA PET additive value for significant prostate cancer (sPCa) diagnosis in men with negative/equivocal MRI
• Detailed Description: This open label, phase III, multi-centre, randomised trial with a non-inferiority objective will evaluate the additive diagnostic value of PSMA PET for men with negative/equivocal MRI in the diagnosis of significant prostate cancer. Patients with a clinical suspicion of prostate cancer with PI-RADS 2 or 3 on MRI, meeting all the inclusion and none of the exclusion criteria will be randomised into experimental and control arms. Patients in the experimental arm would be subjected to Pelvic PSMA PET/CT, wherein the PSMA negative patients would not undergo biopsy as opposed to PSMA positive patients who will be subjected to Transperineal targeted prostate biopsy. Whereas patients in the control arm will only receive Standard of Care (SOC) with no additional imaging (PSMA PET) and will undergo Transperineal template prostate biopsy. The co-primary objectives are to assess (1) the percentage of men with sPCa in the experimental arm (transperineal targeted biopsy) compared to the control arm (transperineal template biopsy) defined as the presence of a single biopsy core indicating disease Gleason score (GS) 3+4(>10%)=7, grade group (GG) 2, and (2) the percentage of men who avoid transperineal prostate biopsy between both arms. The secondary objectives include determining the percentage of clinically insignificant PCa on targeted biopsy (experimental arm) versus transperineal template biopsy (control arm); estimating the difference in complications from transperineal prostate biopsy between both arms; the health economics impact between the experimental and control arms; estimating the mean difference between both arms in change from baseline in health-related quality of life (QoL); estimating the mean difference between both arms at each time point in generalised anxiety and cancer worry.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic
• Condition: Prostate Cancer

Intervention

• Diagnostic Test: PSMA PET/CT
  PSMA PET/CT (limited to the pelvis)
• Procedure: Transperineal template prostate biopsy
  Transperineal template prostate biopsies will be performed as per treating urologist's usual practice. No specific template for biopsy is prescribed for the purposes of the study. However, template sampling of the prostate is required, with a minimum of 12 cores, dependent on prostate volume. MRI will be available for any additional targeted biopsies required. Transperineal template biopsies must be labelled appropriately and sent for histopathological analysis.
• Procedure: Transperineal targeted prostate biopsy
  If the PSMA PET/CT is normal, transperineal prostate biopsy would be omitted If the PSMA PET/CT is abnormal, transperineal prostate biopsies would be performed targeting the MRI (done prior to study) and PSMA PET/CT images

Study Arms

• Experimental: Experimental
  Pelvic PSMA PET ± transperineal targeted prostate biopsy
  Interventions:

  • Diagnostic Test: PSMA PET/CT
  • Procedure: Transperineal targeted prostate biopsy
• Control
  No pelvic PSMA PET + transperineal template prostate biopsy
  Intervention: Procedure: Transperineal template prostate biopsy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 30, 2021): 660
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2028
• Estimated Primary Completion Date: March 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients must meet all the following criteria for study entry:

  1. Males aged ≥ 18 years at the time of consent
  2. No previously diagnosed prostate cancer
  3. No previous prostate biopsy

  4. Having undergone MRI within 9 months prior to randomisation and meet one of the following criteria:

     • PI-RADS 2 AND ≥1 red flag defined as:

       • PSA density >0.1
       • Abnormal DRE
       • Strong family history (1 first degree relative or ≥2 second degree)
       • BRCA mutation
       • PSA >10
       • PSA doubling time <36 months
       • PSA velocity >0.75/year
     • PI-RADS 3
  5. Intention for prostate biopsy
  6. Willing and able to comply with all study requirements

Exclusion Criteria:

• Patients who meet any of the following criteria will be excluded from study entry:

  1. Having a PSA >20ng/ml
  2. Having ≥ cT3 on DRE
  3. Significant morbidity that, in the judgement of the investigator, would limit compliance with study protocol

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes
• Gender Eligibility Description: Males aged ≥ 18 years at the time of consent

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Gaurav Sharma; +61 3 8559 6830; Gaurav.Sharma@petermac.org

Contact: Annette VanDer Heyden; +61488048792; Annette.VanDerHeyden@petermac.org

• Listed Location Countries: Australia

Administrative Information

• NCT Number: NCT05154162
• Other Study ID Numbers: 20/043
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Peter MacCallum Cancer Centre, Australia
• Original Responsible Party: Same as current
• Current Study Sponsor: Peter MacCallum Cancer Centre, Australia
• Original Study Sponsor: Same as current
• Collaborators: St Vincent's Hospital, Sydney

Investigators

• Principal Investigator: Michael Hofman; Peter MacCallum Cancer Centre, Australia
• Principal Investigator: Louise Emmett; St Vincent's Sydney
• Principal Investigator: Mark Frydenberg; Cabrini Health
• Principal Investigator: Sze-Ting Lee; Austin Health
• Principal Investigator: Matthew Roberts; Royal Brisbane and Women's Hospital
• Principal Investigator: Yang Du; Royal Adelaide Hospital

• PRS Account: Peter MacCallum Cancer Centre, Australia
• Verification Date: July 2023