PSMA-Guided PET Scans for Prostate Cancer

(P-GAP Trial)

Recruiting at 2 trial locations

Overseen By Alexander Tamm, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Alberta

Disqualifiers: Weight >250 kg, eGFR <40, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

138 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this phase 2 multicenter randomized controlled trial is to study the accuracy of second generation prostate specific membrane antigen (PSMA) positron emission tomography (PET; utilizing 18F-PSMA-1007) compared to standard of care multiparametric MRI and MRI targeted-prostate biopsy for staging in patients diagnosed with unilateral prostate cancer who are eligible for focal therapy. The main question it aims to answer is: Can PSMA PET improve diagnostic accuracy for the primary staging of Prostate Cancer for patients undergoing focal therapy thereby reducing residual and recurrence disease? Participants who are eligible by current standard of care diagnostic workup will undergo 1:1 randomization to PSMA PET scan or no further imaging. Those diagnosed with bilateral disease by PSMA PET will be ineligible for focal therapy and be referred for radical therapy. Men with unilateral disease on PSMA PET and those randomized to no further imaging will then undergo focal therapy. All men undergoing focal therapy will receive PSMA PET, MRI, and combined targeted and systematic biopsy 12 months after ablation. The primary outcome will be the detection of Gleason Grade Group 2 or higher prostate cancer in men 12 months after hemigland ablation.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have had prior androgen deprivation therapy or radiation therapy to the prostate gland, you would not be eligible for this trial.

What data supports the effectiveness of the treatment PSMA-Guided Ablation of the Prostate, PSMA PET, 18F-PSMA-1007 PET/CT for prostate cancer?

Research shows that 18F-PSMA-1007 PET/CT is effective in detecting prostate cancer, especially in cases of early recurrence, due to its ability to provide clear images without interference from urinary activity. This imaging technique has a higher detection rate for recurrent prostate cancer compared to traditional methods, which can lead to more accurate treatment decisions. ^{1 2 3 4 5}

Is 18F-PSMA-1007 PET/CT safe for humans?

The studies on 18F-PSMA-1007 PET/CT, used for imaging prostate cancer, have primarily focused on its effectiveness and biodistribution, but they also provide some safety data. In a trial involving healthy volunteers and prostate cancer patients, the safety of 18F-PSMA-1007 was evaluated, suggesting it is generally safe for human use. ^{3 6 7 8 9}

How is the PSMA-Guided Ablation of the Prostate treatment different from other prostate cancer treatments?

The PSMA-Guided Ablation of the Prostate treatment uses a special imaging technique called 18F-PSMA-1007 PET/CT, which is unique because it provides clearer images of the prostate area by avoiding interference from urine. This is due to its delayed urinary clearance and excretion through the liver, making it more effective in detecting prostate cancer recurrences compared to other imaging methods. ^{1 3 10 11 12}

Eligibility Criteria

Men over 50 with a PSA level under 15, diagnosed with unilateral prostate cancer of Gleason Grade Group 2 or 3 and clinical stage less than T2b. They should be eligible for focal therapy after standard diagnostic procedures.

Inclusion Criteria

My cancer is in an early stage and has not grown deeply.

My biopsy shows I have a certain level of prostate cancer.

I am over 50 years old.

Exclusion Criteria

My kidney function is low, or I've had a severe reaction to CT dye.

I cannot lie flat for 30 minutes.

Unable to obtain consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomization and Imaging

Participants undergo randomization to either PSMA PET scan or no further imaging. Those with bilateral disease on PSMA PET are ineligible for focal therapy.

1-2 weeks

1 visit (in-person)

Focal Therapy

Participants with unilateral disease undergo hemigland ablation.

1 week

1 visit (in-person)

Follow-up

Participants receive PSMA PET, MRI, and combined targeted and systematic biopsy to assess the presence of clinically significant prostate cancer.

12 months

1 visit (in-person)

Long-term Follow-up

Participants are monitored for quality of life outcomes and economic analysis through study completion.

5 years

Every 3 months for first year, then every 6 months to 1 year

Treatment Details

Interventions

• PSMA-Guided Ablation of the Prostate

Trial Overview This trial is testing the accuracy of a new PSMA PET scan against the usual MRI and biopsy methods in staging prostate cancer before focal therapy. Participants will either receive this new scan or no additional imaging to see if it better predicts who's suitable for treatment.

Participant Groups

Group I: PSMA PET Experimental Treatment 1 Intervention

These patients will have been diagnosed with unilateral prostate cancer by standard of care diagnostic tests deemed eligible and interested in focal therapy. These patients will be randomized to undergo a single \[18\]F-PSMA-1007 PET/CT or PET/MRI scan prior to focal therapy. If they are diagnosed with bilateral disease, they will be ineligible for focal therapy and be referred for radical therapy. Those with unilateral disease will then proceed to focal therapy. They will then receive PSMA PET, MRI, and combined targeted and systematic biopsy 12 months after ablation Intravenous bolus injection of 4 MBq/kg +/- 10% of \[18\]F-PSMA-1007, up to a maximum of 400 MBq.

Group II: No Additional Imaging Active Control 1 Intervention

These patients will have been diagnosed with unilateral prostate cancer by standard of care diagnostic tests deemed eligible and interested in focal therapy. These patients will undergo no further testing and will undergo focal therapy. They will then receive PSMA PET, MRI, and combined targeted and systematic biopsy 12 months after ablation. Intravenous bolus injection of 4 MBq/kg +/- 10% of \[18\]F-PSMA-1007, up to a maximum of 400 MBq.

PSMA-Guided Ablation of the Prostate is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as 18F-PSMA-1007 for:

• Prostate cancer staging
• Detection of biochemical recurrence

Approved in United States as 18F-PSMA-1007 for:

• Prostate cancer staging
• Detection of biochemical recurrence

Approved in Canada as 18F-PSMA-1007 for:

• Prostate cancer staging
• Detection of biochemical recurrence

Who Is Running the Clinical Trial?

University of Alberta

Lead Sponsor

Trials

957

Recruited

437,000+

Findings from Research

In a study of 46 prostate cancer patients with early biochemical recurrence, 18F-PSMA-1007 PET/CT successfully identified recurrence in 52.2% of cases, demonstrating its effectiveness in detecting cancer that may be missed by conventional imaging.

The use of 18F-PSMA-1007 is particularly beneficial for patients with lower PSA levels, as it detected recurrence in 72.2% of patients with PSA levels greater than 2 ng/ml, and it revealed positive findings in 29.2% of patients previously considered negative or equivocal on other imaging methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Diagnostic Performance of 18F-PSMA-1007 PET/CT in Prostate Cancer Patients with Early Recurrence after Definitive Therapy with a PSA Lengana, T., Lawal, I., Janse Van Rensburg, C., et al.[2022]

A systematic review of 15 studies involving 853 patients found that 18F-PSMA-1007 PET/CT or PET/MRI has a high detection rate of 81.3% for biochemical recurrent prostate cancer, even in patients with low PSA levels.

The detection rate of 18F-PSMA-1007 imaging is influenced by serum PSA values, indicating that higher PSA levels may correlate with better detection outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-PSMA-1007 PET in Biochemical Recurrent Prostate Cancer: An Updated Meta-Analysis. Ferrari, M., Treglia, G.[2022]

The PET tracer 18F-PSMA 1007 was found to be safe and well tolerated in both healthy volunteers and prostate cancer patients, with no serious adverse events reported during the study.

In terms of diagnostic effectiveness, 18F-PSMA 1007 demonstrated high accuracy in detecting prostate cancer, achieving a sensitivity of 80% and a positive predictive value of 100% in patients with untreated preoperative prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients. Tateishi, U., Kimura, K., Tsuchiya, J., et al.[2023]

PSMA-targeted PET/CT is a highly sensitive and specific imaging technique that significantly improves the detection and management of recurrent prostate cancer compared to conventional imaging methods.

This advanced imaging allows for better patient selection for localized salvage therapies and has shown promise in delaying the need for systemic treatments in patients with oligometastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate-specific membrane antigen targeted PET/CT for recurrent prostate cancer: a clinician's guide. Young, S., Liu, W., Zukotynski, K., et al.[2022]

PSMA PET imaging, particularly with 68Ga-PSMA-11, is highly effective for detecting prostate cancer metastases and has been shown to change clinical management decisions, leading to increased use of targeted therapies like radiotherapy and surgery.

In cases of prostate cancer recurrence, PSMA PET demonstrates higher detection rates than other imaging methods, especially at low prostate-specific antigen levels, making it a valuable tool for guiding treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Emerging Clinical Applications of PSMA PET Diagnostic Imaging for Prostate Cancer. Farolfi, A., Calderoni, L., Mattana, F., et al.[2021]

The novel 18F-labelled PSMA-1007 ligand shows a significant increase in uptake in prostate cancer lesions over time, with maximum standardized uptake (SUVmax) rising from 10.98 at 60 minutes to 15.51 at 120 minutes post-injection, indicating improved detection capabilities.

Low accumulation of the tracer in the urinary bladder enhances the visibility of nearby prostate cancer lesions, although increased uptake in the liver may reduce the sensitivity for detecting liver metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-PSMA-1007 PET/CT at 60 and 120 minutes in patients with prostate cancer: biodistribution, tumour detection and activity kinetics. Rahbar, K., Afshar-Oromieh, A., Bögemann, M., et al.[2019]

Imaging with [18F]PSMA-1007 at 2 hours post-injection significantly detected more pelvic lymph nodes and bone metastases compared to imaging at 1 hour, which could influence treatment decisions for prostate cancer patients.

In a study of 195 patients, 6.1% showed a higher N- or M-stage after 2 hours, indicating that longer imaging time may provide more accurate staging and better assessment of disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET/CT imaging 2&#160;h after injection of [18F]PSMA-1007 can lead to higher staging of prostate cancer than imaging after 1&#160;h. Hvittfeldt, E., Bitzén, U., Minarik, D., et al.[2023]

In a study involving 12 prostate cancer patients, the new tracer 18 F-PSMA-1007 demonstrated high uptake in organs such as the liver, kidneys, and salivary glands, indicating its potential effectiveness for imaging prostate cancer.

The effective radiation dose from 18 F-PSMA-1007 was calculated to be between 6.0-8.0 mSv for an average patient, which provides important safety information for its use in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biokinetics and dosimetry of 18 F-PSMA-1007 in patients with prostate cancer. Hvittfeldt, E., Bjöersdorff, M., Brolin, G., et al.[2023]

In a study of 102 patients with recurrent prostate cancer, 18F-PSMA-1007 PET detected significantly more lesions (369) compared to 68Ga-PSMA-11 PET (178), indicating its superior detection efficacy.

However, 18F-PSMA-1007 PET also revealed a higher frequency of benign lesions (245) compared to 68Ga-PSMA-11 PET (52), suggesting that while it is effective in detecting cancer, it may also lead to more false positives, highlighting the need for careful interpretation by trained professionals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matched-Pair Comparison of 68Ga-PSMA-11 PET/CT and 18F-PSMA-1007 PET/CT: Frequency of Pitfalls and Detection Efficacy in Biochemical Recurrence After Radical Prostatectomy. Rauscher, I., Krönke, M., König, M., et al.[2022]

PSMA-based PET-CT imaging using fluorine-18 PSMA-1007 is effective for staging high-risk prostate cancer and locating recurrent disease, offering advantages like hepatobiliary excretion and a longer half-life compared to gallium tracers.

Despite its benefits, there are still some ambiguities and potential pitfalls in interpreting the results of PSMA-1007 imaging, which need to be considered in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorine-18 labelled prostate-specific membrane antigen (PSMA)-1007 positron-emission tomography-computed tomography: normal patterns, pearls, and pitfalls. Foley, RW., Redman, SL., Graham, RN., et al.[2021]

The 18F-PSMA-1007 PET/CT method shows a high detection rate for recurrent prostate cancer, particularly effective in identifying local recurrences and small lymph node metastases that conventional imaging may miss.

While 18F-PSMA-1007 PET/CT is reliable, it has limitations, such as non-specific uptake in bone lesions that can be mistaken for bone metastases, highlighting the need for careful interpretation of results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent Prostate Cancer Diagnostics with 18F-PSMA-1007 PET/CT: A Systematic Review of the Current State. Saule, L., Radzina, M., Liepa, M., et al.[2022]

F-18-PSMA-1007-PET is effective for staging prostate cancer, particularly in identifying seminal vesicle invasion, outperforming mpMRI with a correct staging rate of 90% compared to 76%.

The study suggests that combining F-18-PSMA-1007-PET with mpMRI could enhance the overall accuracy of prostate cancer staging, as mpMRI was better at detecting extracapsular extension (90% vs. 57%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating F-18-PSMA-1007-PET in primary prostate cancer and comparing it to multi-parametric MRI and histopathology. Privé, BM., Israël, B., Schilham, MGM., et al.[2022]

References

1. Germany pubmed.ncbi.nlm.nih.gov

The Diagnostic Performance of 18F-PSMA-1007 PET/CT in Prostate Cancer Patients with Early Recurrence after Definitive Therapy with a PSA [2022]

2. England pubmed.ncbi.nlm.nih.gov

18F-PSMA-1007 PET in Biochemical Recurrent Prostate Cancer: An Updated Meta-Analysis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase I/IIa trial of 18F-prostate specific membrane antigen (PSMA) 1007 PET/CT in healthy volunteers and prostate cancer patients. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Prostate-specific membrane antigen targeted PET/CT for recurrent prostate cancer: a clinician's guide. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Current and Emerging Clinical Applications of PSMA PET Diagnostic Imaging for Prostate Cancer. [2021]

6. Germany pubmed.ncbi.nlm.nih.gov

18F-PSMA-1007 PET/CT at 60 and 120 minutes in patients with prostate cancer: biodistribution, tumour detection and activity kinetics. [2019]

7. England pubmed.ncbi.nlm.nih.gov

PET/CT imaging 2&#160;h after injection of [18F]PSMA-1007 can lead to higher staging of prostate cancer than imaging after 1&#160;h. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Biokinetics and dosimetry of 18 F-PSMA-1007 in patients with prostate cancer. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Matched-Pair Comparison of 68Ga-PSMA-11 PET/CT and 18F-PSMA-1007 PET/CT: Frequency of Pitfalls and Detection Efficacy in Biochemical Recurrence After Radical Prostatectomy. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Fluorine-18 labelled prostate-specific membrane antigen (PSMA)-1007 positron-emission tomography-computed tomography: normal patterns, pearls, and pitfalls. [2021]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Recurrent Prostate Cancer Diagnostics with 18F-PSMA-1007 PET/CT: A Systematic Review of the Current State. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Evaluating F-18-PSMA-1007-PET in primary prostate cancer and comparing it to multi-parametric MRI and histopathology. [2022]