MRI-Guided Prostate SBRT for Prostate Cancer

(ARGOS/CLIMBER Trial)

Recruiting at 1 trial location

Overseen By Lucas Mendez, MD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Must not be taking: Anticoagulants

Disqualifiers: T4 disease, Connective tissue disease, Inflammatory bowel disease, others

Stay on Your Current Meds You can continue your current medications while participating

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 5 fractions

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a prospective Phase I/II protocol enrolling men with either high intermediate-risk or high-risk or very high-risk prostate cancer. All men will have PSMA Targeted PET (using the PSMA targeting ligand PSMA 1007) and multiparametric magnetic resonance imaging (mpMRI) for delineation of intra-prostatic foci of cancer and any involved regional lymph nodes based on high SUV uptake on PET or mpMRI (T2W, DWI/ADC, DCE) appearance suspicious for cancer. Tumour delineation will be performed by fusing the PSMA PET and mpMRI with planning CT simulation images. Fiducial marker implantation for treatment guidance will be mandatory but use of other organs at risk protection strategies (i.e. GU Loc, Space-OAR) will be allowed but not mandatory. Patients will be treated with image-guided SBRT using the fiducial markers for intra-fraction motion management. Dose escalation to imaging defined targets (intra-prostatic and involved nodes on PSMA PET + MRI) will be accomplished through a simultaneous boost technique. Maintaining dose to organs at risk will take precedence over boost dose targets (targeted maximum dose of 50Gy/5 fractions to imaging defined prostatic lesion; 35Gy/5 fractions to imaging defined involved nodes). Cohort extension: We hypothesize that integration of neoadjuvant androgen deprivation therapy will provide for pretreatment cancer downstaging and will allow us to achieve higher target doses to the imaging defined DILs than currently achieve. Additionally, we plan to include a novel sodium MRI protocol into the baseline imaging to compare DIL volumes delineated by this modality to those by mpMRI and PSMA PET and to characterize changes in sodium MRI in response to ADT alone and subsequent radiotherapy

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are on androgen deprivation therapy or if it's unsafe to stop anticoagulation medication for a procedure.

What data supports the effectiveness of the treatment PSMA MRI Guided Prostate SBRT for Prostate Cancer?

Research shows that using PSMA PET and MRI together can help identify specific areas of prostate cancer more accurately, which can improve the targeting of radiation therapy. This approach has been shown to enhance the effectiveness of treatment by focusing on the most affected areas, potentially leading to better outcomes for patients. ^{1 2 3 4 5}

Is MRI-Guided Prostate SBRT safe for humans?

Research on 18F-PSMA-1007, a tracer used in imaging for prostate cancer, has been conducted to assess its safety and radiation exposure in both healthy volunteers and prostate cancer patients, indicating it is generally safe for human use. ^{1 5 6 7 8}

How is the PSMA MRI Guided Prostate SBRT treatment different from other prostate cancer treatments?

The PSMA MRI Guided Prostate SBRT treatment is unique because it uses advanced imaging techniques, specifically PSMA PET and MRI, to precisely target prostate cancer cells with high-dose radiation, potentially improving accuracy and reducing side effects compared to traditional radiation therapies. ^{1 2 4 9 10}

Eligibility Criteria

Men over 18 with high intermediate-risk, high-risk, or very high-risk prostate cancer that hasn't spread beyond the pelvis. They must have no history of prior prostate cancer treatments (except for certain medications), be able to undergo MRI and PSMA PET scans without contraindications like incompatible implants, and not have severe urinary problems or conditions preventing radiotherapy.

Inclusion Criteria

I am older than 18 years.

My prostate cancer is classified as high-intermediate, high, or very-high risk.

My prostate cancer has been confirmed by a tissue examination.

Exclusion Criteria

I cannot undergo intense prostate radiotherapy due to certain health conditions like connective tissue disease.

I have had prostate cancer treatment, but not hormone therapy before joining.

My cancer has spread beyond the pelvic area.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive image-guided SBRT using fiducial markers for intra-fraction motion management with dose escalation to imaging defined targets

5 fractions

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of 6-week and 6-month toxicity

6 months

Long-term Follow-up

Participants are monitored for quality of life and disease-free survival over a 5-year period

5 years

Treatment Details

Interventions

• PSMA MRI Guided Prostate SBRT

Trial Overview The trial is testing a targeted radiation therapy called SBRT guided by PSMA PET scans and mpMRI images in men with specific risk levels of prostate cancer. It involves fusing these images with CT simulations for precise tumor targeting, using fiducial markers for motion management during treatment, and escalating doses to identified targets while protecting surrounding organs.

Participant Groups

Group I: Men with high intermediate to very high risk prostate cancer Experimental Treatment 4 Interventions

Men with high intermediate to very high risk prostate cancer

PSMA MRI Guided Prostate SBRT is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as PSMA MRI Guided Prostate SBRT for:

• High intermediate-risk prostate cancer
• High-risk prostate cancer
• Very high-risk prostate cancer

Approved in United States as PSMA MRI Guided Prostate SBRT for:

• High intermediate-risk prostate cancer
• High-risk prostate cancer
• Very high-risk prostate cancer

Approved in Canada as PSMA MRI Guided Prostate SBRT for:

• High intermediate-risk prostate cancer
• High-risk prostate cancer
• Very high-risk prostate cancer

Who Is Running the Clinical Trial?

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Findings from Research

In a pilot study of 62 patients with suspected or defined prostate cancer, PSMA-PET/MRI imaging led to a change in management strategies for 41.9% of patients, indicating its potential clinical utility in guiding treatment decisions.

The most significant impact of PSMA-PET/MRI was observed in patients with biochemical recurrent prostate cancer, particularly those with PSA levels between 0.5 and 1 ng/ml, suggesting that this imaging technique can help refine treatment approaches in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Utility of 18F-PSMA-1007 Positron Emission Tomography/Magnetic Resonance Imaging in Prostate Cancer: A Single-Center Experience. Liu, A., Zhang, M., Huang, H., et al.[2022]

In a study of 13 men with localized prostate cancer, combining PSMA-directed PET and mpMRI imaging revealed that over half of the identified lesions (53.8%) were discordant, meaning they were detected by only one of the imaging methods, highlighting the importance of using both for comprehensive disease identification.

Planning radiation therapy using both imaging techniques resulted in better coverage of all identified lesions while maintaining safety limits for surrounding tissues, suggesting that this combined approach could enhance treatment effectiveness for localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using 18F-DCFPyL Prostate-Specific Membrane Antigen-Directed Positron Emission Tomography/Magnetic Resonance Imaging to Define Intraprostatic Boosts for Prostate Stereotactic Body Radiation Therapy. Floberg, JM., Wells, SA., Ojala, D., 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]

In a study of 64 patients with prostate cancer local recurrences treated with single-fraction stereotactic body radiotherapy (SBRT), PSA levels significantly decreased after treatment, indicating effective tumor control.

The treatment showed promising safety and efficacy, with a 3-year progression-free survival rate of 51.2% and only 9% of patients experiencing mild toxicities, suggesting that SBRT can be a viable option for patients with prior treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-fraction prostate-specific membrane antigen positron emission tomography- and multiparametric magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer local recurrences. Ehret, F., Hofmann, T., Fürweger, C., et al.[2023]

The study demonstrated that a comprehensive whole-body 18F-PSMA-1007-PET/MRI protocol is feasible and reproducible for imaging prostate cancer in eight high-risk patients, effectively detecting dominant lesions and providing complementary staging information.

The results showed strong correlation between SUVmean values from PET/CT and PET/MRI, indicating that this combined imaging approach can enhance the accuracy of prostate cancer assessment while minimizing artifacts, thus improving patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous whole-body 18F-PSMA-1007-PET/MRI with integrated high-resolution multiparametric imaging of the prostatic fossa for comprehensive oncological staging of patients with prostate cancer: a pilot study. Freitag, MT., Kesch, C., Cardinale, J., et al.[2019]

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]

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]

In a study involving 20 patients with castration-sensitive oligorecurrent prostate cancer, PSMA-PET/CT guided SBRT using a 1.5 T MRI-Linac was found to be safe and well tolerated, with no acute severe toxicities reported.

The treatment resulted in a significant reduction in PSA levels, with 6 patients showing a partial response and 10 achieving a complete response, indicating promising effectiveness of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for oligometastatic castration sensitive prostate cancer using 1.5 T MRI-Linac: preliminary data on feasibility and acute patient-reported outcomes. Mazzola, R., Cuccia, F., Figlia, V., et al.[2021]

In a study of 35 patients with locally recurrent prostate cancer, PSMA PET and MRI-guided stereotactic body radiotherapy (SBRT) resulted in a median progression-free survival of 52.2 months, indicating effective long-term disease control.

The treatment was associated with low rates of toxicity, as 54.3% of patients experienced no acute side effects and 79.4% had no late toxicity, making it a safer alternative to more invasive treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PSMA PET-based stereotactic body radiotherapy for locally recurrent prostate cancer after definitive first-line therapy. Gruen, A., Tegel, K., Kluge, A., et al.[2023]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Utility of 18F-PSMA-1007 Positron Emission Tomography/Magnetic Resonance Imaging in Prostate Cancer: A Single-Center Experience. [2022]

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

Using 18F-DCFPyL Prostate-Specific Membrane Antigen-Directed Positron Emission Tomography/Magnetic Resonance Imaging to Define Intraprostatic Boosts for Prostate Stereotactic Body Radiation Therapy. [2023]

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

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

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

Single-fraction prostate-specific membrane antigen positron emission tomography- and multiparametric magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer local recurrences. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Simultaneous whole-body 18F-PSMA-1007-PET/MRI with integrated high-resolution multiparametric imaging of the prostatic fossa for comprehensive oncological staging of patients with prostate cancer: a pilot study. [2019]

6. England pubmed.ncbi.nlm.nih.gov

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

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

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

8. 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]

9. Italy pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for oligometastatic castration sensitive prostate cancer using 1.5 T MRI-Linac: preliminary data on feasibility and acute patient-reported outcomes. [2021]

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

PSMA PET-based stereotactic body radiotherapy for locally recurrent prostate cancer after definitive first-line therapy. [2023]