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

NCT ID: NCT05154162

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 660 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-02
• Study Completion Date: 2027-08-31

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.

Conditions

Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Experimental

Pelvic PSMA PET ± transperineal targeted prostate biopsy

Group Type: EXPERIMENTAL

PSMA PET/CT

Intervention Type: DIAGNOSTIC_TEST

PSMA PET/CT (limited to the pelvis)

Transperineal targeted prostate biopsy

Intervention Type: PROCEDURE

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

Control

No pelvic PSMA PET + transperineal template prostate biopsy

Group Type: OTHER

Transperineal template prostate biopsy

Intervention Type: PROCEDURE

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.

Interventions

PSMA PET/CT

PSMA PET/CT (limited to the pelvis)

Intervention Type: DIAGNOSTIC_TEST

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.

Intervention Type: 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

Intervention Type: PROCEDURE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

St Vincent's Hospital, Sydney

OTHER

Sponsor Role: collaborator

Peter MacCallum Cancer Centre, Australia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Hofman

Role: PRINCIPAL_INVESTIGATOR

Peter MacCallum Cancer Centre, Australia

Louise Emmett

Role: PRINCIPAL_INVESTIGATOR

St Vincent's Sydney

Mark Frydenberg

Role: PRINCIPAL_INVESTIGATOR

Cabrini Health

Sze-Ting Lee

Role: PRINCIPAL_INVESTIGATOR

Austin Health

Matthew Roberts

Role: PRINCIPAL_INVESTIGATOR

Royal Brisbane and Women's Hospital

Yang Du

Role: PRINCIPAL_INVESTIGATOR

Royal Adelaide Hospital

Locations

St Vincent's Hospital

Sydney, New South Wales, Australia

Royal Brisbane and Women's Hospital

Brisbane, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Austin Health

Melbourne, Victoria, Australia

Cabrini Health

Melbourne, Victoria, Australia

Countries

Australia

References

Buteau JP, Moon D, Fahey MT, Roberts MJ, Thompson J, Murphy DG, Papa N, Mitchell C, De Abreu Lourenco R, Dhillon HM, Kasivisvanathan V, Francis RJ, Stricker P, Agrawal S, O'Brien J, McVey A, Sharma G, Levy S, Ayati N, Nguyen A, Lee SF, Pattison DA, Sivaratnam D, Frydenberg M, Du Y, Titus J, Lee ST, Ischia J, Jack G, Hofman MS, Emmett L. Clinical Trial Protocol for PRIMARY2: A Multicentre, Phase 3, Randomised Controlled Trial Investigating the Additive Diagnostic Value of [68Ga]Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Negative or Equivocal Multiparametric Magnetic Resonance Imaging for the Diagnosis of Clinically Significant Prostate Cancer. Eur Urol Oncol. 2024 Jun;7(3):544-552. doi: 10.1016/j.euo.2023.11.008. Epub 2023 Dec 6.

Reference Type: DERIVED

PMID: 38061976 (View on PubMed)

Other Identifiers

20/043

Identifier Type: -

Identifier Source: org_study_id