PSMA PET with MRI to detect prostate cancer

A Single Arm, Multicenter, Prospective, Open Label, Longitudinal Phase 3 Study of Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) Combined With Magnetic Resonance Imaging (MRI) Compared to Standard of Care (SOC) for the Detection of Prostate Cancer (PCa).

This study will test if adding PSMA PET to MRI helps find clinically significant prostate cancer better than usual care in men who are about to have a prostate biopsy.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 204 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Telix Pharmaceuticals (Innovations) Pty Limited (industry)
• Drugs / interventions: radiation
• Locations: 1 site (Melbourne N., Victoria)
• Trial ID: NCT07052214 on ClinicalTrials.gov

What this trial studies

This is a multicenter, prospective, open-label Phase 3 single-arm study enrolling 204 men across sites in the United States and Australia. All participants receive both MRI and 68Ga-PSMA-11 PET imaging, followed by a standard 12-core template biopsy as the histopathologic reference, with optional targeted biopsies for lesions seen on MRI or PSMA PET. Imaging findings will be compared to biopsy results to determine whether combining PSMA PET with MRI improves detection of clinically significant prostate cancer. Imaging and biopsy choices remain at the treating clinician's discretion, and participants who do not undergo the planned biopsy are discontinued from the study.

Who should consider this trial

Good fit: Men aged 18 or older with clinical suspicion of prostate cancer who are biopsy‑naive and scheduled for template biopsy based on recent MRI (PI‑RADS 3–4) or on non‑imaging risk factors (eg, elevated PSA, high PSA density, or abnormal DRE) are ideal candidates.

Not a fit: Men who have already had a prostate biopsy, have known prostate cancer, or are not planning to undergo biopsy are unlikely to receive benefit from this study.

Why it matters

Potential benefit: If successful, combining PSMA PET with MRI could improve detection of clinically significant prostate cancer and reduce unnecessary biopsies.

How similar studies have performed: Earlier and smaller studies have shown promising results for PSMA PET plus MRI in improving detection and localization of significant prostate cancer, but large-scale Phase 3 validation remains limited.

Eligibility criteria

Inclusion Criteria:

1. Male, at least 18 years old.
2. Have a clinical suspicion of PCa, and will undergo template biopsy, based on either: an initial MRI examination (PI-RADS 3-4) within 3 months (92 days) before enrollment, or no MRI evidence (PI-RADs 1-2) within 3 months (92 days) before enrollment, but a clinician indicated intent to proceed with template biopsy due to non-imaging risk factors.

These are non-imaging risk factors that would lead a patient to be considered for a template biopsy (including but not exclusive to):

1. Persistently elevated or rising PSA i. PSA ≥ 3.0 ng/mL ii. Rising PSA velocity (e.g., \>0.35-0.75 ng/mL/year over 2-3 years) is also considered suspicious, especially in men with PSA\<10ng/mL.
2. High PSA density (PSAD) i. PSA density \> 0.15 ng/mL/cm³ is considered high-risk for csPCa. ii. Calculated as PSA (ng/mL) divided by prostate volume (from MRI).
3. Abnormal digital rectal examination (DRE) i. abnormal findings include:

   1. Nodules
   2. Induration
   3. Asymmetry
   4. Fixation of the prostate ii. An abnormal DRE in any PSA range (including \<3 ng/mL) increases cancer suspicion.

b) Strong family history of prostate cancer: i. First-degree relative (father or brother) with PCa ii. Any relative diagnosed at \<65 years of age iii. Multiple affected relatives iv. Known hereditary cancer syndromes (e.g., BReast CAncer gene \[BRCA\]1/2, Homeobox protein Hox-B13 \[HOXB13\] mutations) c) Other high-risk biomarkers i. 4Kscore: ≥ 7.5-10% risk of high-grade PCa ii. PHI (Prostate Health Index): ≥ 35 suggests elevated risk iii. Prostate Cancer Antigen 3 (PCA3) Score: ≥ 35 considered positive and associated with increased risk of PCa.

iv. Any other established biomarker with values in the high-risk range d) Clinical presentation i. Symptoms suggestive of locally advanced disease (e.g., urinary obstruction, bone pain) ii. Prior negative MRI with ongoing clinical concern 3. Prostate biopsy naïve participants. 4. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2 per FDA guidelines. 5. Have the capacity to understand the study and be able and willing to comply with all protocol requirements. 6. Provides consent for anatomical template with/without targeted biopsy based on clinical risk, MRI and PSMA PET result. 7. Participants must comply with the radiation protection rules (including hospital admissions and isolation) that are used by the treating institution to protect their contacts and the general public, especially if a female partner of the participant is or could be pregnant.

8\. Must agree to practice adequate precautions to prevent pregnancy in a female partner and to avoid potential problems associated with radiation exposure to the unborn child (Recommendations related to contraception and pregnancy testing in clinical trials Version 1.1, (CTFG \[Clinical Trial Facilitation Group\], 2020). Details of contraceptive measures to be taken by male participants and their female partners are described in Appendix 4 of the Protocol.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. Has had prior treatment for PCa or prior diagnosis of csPCa.
2. Obvious metastatic disease on prior conventional imaging.
3. Previous diagnosis of cancer of any primary origin (excluding basal cell carcinoma or squamous cell carcinoma of the skin that has undergone potentially curative therapy).
4. Active prostate infection, or urinary test results suggestive of an active urinary tract infection, evident on medical history, within 4 weeks of enrollment.
5. Prior pelvic irradiation
6. Demonstrate radiographic findings of PI-RADS 5.
7. Has abnormalities in physical examination and protocol-specified clinical laboratory tests during the Screening Period that, in the judgment of the investigator, could affect safety or compliance; and/or is deemed not suitable for participating in this trial in the opinion of the investigator.
8. Unable to understand or is unwilling to sign a written informed consent document or to follow investigational procedures in the opinion of the investigator.
9. Is unable to attain or remain in a supine position while a PET/CT scan is being performed or unable to tolerate a PET/CT scan
10. Unable or unwilling to undergo clinical prostate biopsy, has known allergies, hypersensitivity, or intolerance to the investigational drug/comparator or its excipients.
11. Have prior use of radionuclides with an interval of less than 10 effective half-lives before the administration of 68Ga-PSMA-11.
12. Is participating or plans to participate in any experimental drug or device trial during the study period that are considered outside of therapeutic SOC. Studies involving modifications of sequencing or timing of therapeutic regimens/interventions would be deemed eligible to enroll

Where this trial is running

Melbourne N., Victoria

• Australian Prostate Centre — Melbourne N., Victoria, Australia (RECRUITING)

Conditions: PCA, Prostate Cancer, Prostatic Neoplasm, PSMA PET, Diagnostic Imaging, Elevated PSA, Positron Emission Tomography, Prostate Biopsy