MR-guided Radiotherapy for Recurrent Prostate Cancer

Overseen By Alejandro Berlin, MD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Hormonal therapy

Disqualifiers: Non-skin malignancy, Metastatic disease, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 months

100 Participants Needed

Trial Summary

What is the purpose of this trial?

In the clinical scenario of recurrent prostate cancer (PCa) post local therapy, current standard studies (bone scan and computed tomography) commonly fail to identify the recurrent disease location. In this study the investigator aims to prospectively map recurrent disease with the unique combination of whole-body MR anatomical imaging combined with a new high-sensitivity and PCa-specific PET probe (PSMA-targeted: \[18F\]DCFPyL) to provide precise localization information to target disseminated tumor deposits in men presenting with rising PSA after prostatectomy and radiotherapy (maximal local therapies). Moreover, we will consequently treat all identified disease with image-guided stereotactic ablative radiotherapy (SABR), which has shown tantalizing results achieving excellent tumor eradication rates with minimal toxicities. This study is uniquely positioned to enable the discovery of new biomarkers and the correlation of prognostic tests (e.g. genomic signatures) from the initial prostatectomy specimen with the PET-MR/CT imaging results and curative-intent treatment outcomes. The significance of the proposed work towards a measurable impact in PCa care is important to emphasize. The study team believes this novel curative-intent approach will transform lives, as opposed to therapies that transiently impact incurable disease stages. Herein, the focus is on patients at the earliest point of the disease spectrum of recurrent PCa after curative-intent treatments. Our hypothesis is that PSMA-targeted \[18F\]DCFPyL PET-MR/CT allows earlier detection and localization of defined metastatic targets in these patients, at a stage amenable to image-guided curative-intent therapy.

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 have used any form of hormonal therapy in the past 12 months or plan to start it when enrolling.

What data supports the effectiveness of the treatment Stereotactic Ablative Radiotherapy, Stereotactic Body Radiotherapy (SBRT), Stereotactic Ablative Body Radiotherapy for recurrent prostate cancer?

Research shows that Stereotactic Body Radiotherapy (SBRT) is increasingly used for prostate cancer, with studies indicating it can improve patient outcomes and potentially serve as a curative treatment for local recurrence. Additionally, SBRT has been associated with favorable toxicity and quality of life outcomes in patients. ^{1 2 3 4 5}

Is MR-guided radiotherapy safe for treating prostate cancer?

Research shows that stereotactic body radiotherapy (SBRT), which is similar to MR-guided radiotherapy, is generally safe for treating prostate cancer. Studies have reported on its safety and low toxicity levels, even over long periods, for various prostate cancer conditions. ^{2 6 7 8 9}

How is MR-guided Stereotactic Ablative Radiotherapy (SBRT) different from other treatments for recurrent prostate cancer?

MR-guided Stereotactic Ablative Radiotherapy (SBRT) is unique because it uses advanced imaging to precisely target and deliver high doses of radiation to the tumor while minimizing exposure to surrounding healthy tissue, which is particularly beneficial for patients who have already received radiation therapy. This approach can potentially reduce side effects and improve outcomes compared to traditional treatments like surgery or hormone therapy, which may have significant risks and side effects. ^{2 3 10 11 12}

Research Team

Alejandro Berlin, MD

Principal Investigator

Princess Margaret Cancer Centre - University Health Network

Eligibility Criteria

This trial is for men with prostate cancer recurrence after surgery and radiotherapy, who have rising PSA levels but no visible metastases on scans. They should be in good health overall, able to lie still for imaging and treatment, not on hormone therapy recently or planning to start it, and without severe kidney issues or certain blood disorders.

Inclusion Criteria

My cancer has not spread to other parts of my body.

I will start hormone therapy when my PSA level is 6.0ng/ml or higher.

I don't have other major health issues that would prevent me from undergoing curative treatments.

Exclusion Criteria

I have never had cancer that wasn't skin cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging and Localization

Participants undergo whole-body MR anatomical imaging combined with PSMA-targeted [18F]DCFPyL PET to map recurrent disease

1-2 weeks

1 visit (in-person)

Treatment

Identified lesions are treated with image-guided stereotactic ablative radiotherapy (SABR) or surgery

6 months

Follow-up

Participants are monitored for safety, effectiveness, and biochemical response after treatment

6 months

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• Stereotactic Ablative Radiotherapy

Trial Overview The study tests a new PET/MRI scan using [18F]DCFPyL to find tiny cancer spread post-prostatectomy that standard scans can't see. Men with detected cancer spots will then receive precise Stereotactic Ablative Radiotherapy (SABR) aimed at eradicating these tumors.

Participant Groups

Group I: [18F] DCFPyL PET/MRI Experimental Treatment 2 Interventions

\[18F\] DCFPyL PET/MRI scans for patients with recurrent disease after radical prostatectomy and adjuvant/salvage radiotherapy. Lesions identified through \[18F\] DCFPyL PET/MRI will be treated with stereotactic ablative radiotherapy (SABR) or surgery.

Stereotactic Ablative Radiotherapy is already approved in European Union, United States, United Kingdom for the following indications:

Approved in European Union as Stereotactic Ablative Radiotherapy for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Approved in United States as Stereotactic Ablative Radiotherapy for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Approved in United Kingdom as Stereotactic Ablative Radiotherapy for:

• Early-stage non-small cell lung cancer
• Liver cancers
• Kidney cancers
• Bone metastasis
• Spinal metastasis
• Prostate cancers

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Findings from Research

This multicenter phase I/II study aims to evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for patients with localized prostate cancer recurrence after previous radiotherapy, involving at least 47 participants.

The primary goal is to determine the optimal dose of SBRT while monitoring for dose-limiting toxicities, with the secondary aim of assessing the treatment's effectiveness in achieving biochemical relapse-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GETUG-AFU 31: a phase I/II multicentre study evaluating the safety and efficacy of salvage stereotactic radiation in patients with intraprostatic tumour recurrence after external radiation therapy-study protocol. Pasquier, D., Le Deley, MC., Tresch, E., et al.[2020]

In a study of 200 prostate cancer patients treated with MR-guided stereotactic body radiotherapy (SBRT), the treatment demonstrated low acute toxicity, with the most common side effect being mild urinary issues in 31% of patients.

The therapy resulted in a significant decrease in Prostate Specific Antigen (PSA) levels in 99% of patients, indicating effective treatment outcomes, while real-time MRI monitoring ensured precise targeting during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of the first 200 patients with prostate cancer treated with MRI-Linac at Assuta MC. Gelbart Pridan, O., Ben David, MA., Zalmanov, S., et al.[2023]

In a study involving 20 prostate cancer patients treated with Adaptive Stereotactic Body Radiotherapy (SBRT), the delivered dose was confirmed to be adequate, ensuring that the target area received at least 95% of the prescribed dose while minimizing exposure to surrounding organs.

The study demonstrated that both the daily re-computed doses and cumulative doses were consistent, indicating that the online MRI guidance effectively maintained treatment accuracy despite potential prostate motion during the longer session times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive SBRT by 1.5 T MR-linac for prostate cancer: On the accuracy of dose delivery in view of the prolonged session time. Ruggieri, R., Rigo, M., Naccarato, S., et al.[2021]

In a study involving 51 prostate cancer patients treated with stereotactic body radiotherapy (SBRT), the treatment showed promising outcomes with manageable toxicity levels, as no patients experienced severe (grade 3+) side effects during the initial follow-up period.

The median follow-up of 14.5 months revealed a low prostate-specific antigen level of 1.3 ng/ml at 13-18 months post-treatment, indicating effective disease control in this cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate stereotactic body radiotherapy—first UK experience. Tree, AC., Ostler, P., Hoskin, P., et al.[2022]

In a study of 26 patients with low- or intermediate-risk prostate adenocarcinoma, stereotactic body radiation therapy (SBRT) showed excellent biochemical control with no observed failures after a median follow-up of 59.5 months.

The treatment resulted in manageable late toxicity, with only 11.5% of patients experiencing significant genitourinary or gastrointestinal side effects, and patient-reported quality of life remained stable compared to pre-treatment levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial. Maas, JA., Dobelbower, MC., Yang, ES., et al.[2023]

Stereotactic body radiotherapy (SBRT) is shown to be safe and effective for treating node-positive prostate cancer, with a median follow-up of 30 months revealing no severe gastrointestinal toxicities and manageable genitourinary side effects.

In a study of 60 patients, SBRT resulted in a 3-year overall survival rate of 89% and a biochemical failure-free survival rate of 77%, indicating promising long-term outcomes even in patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer. Telkhade, T., Murthy, V., Kanala, TS., et al.[2021]

Stereotactic body radiation therapy (SBRT) demonstrated high local control rates (96.0% at 2 years) and was well tolerated among 75 patients with oligometastases of prostate cancer, indicating its efficacy and safety as a treatment option.

The study found that SBRT could effectively manage both metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC), providing a potential alternative to delay androgen deprivation therapy (ADT) for mHSPC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-Term Outcomes and Clinical Efficacy of Stereotactic Body Radiation Therapy (SBRT) for Oligometastases of Prostate Cancer in China. Xu, C., Zhao, X., Ju, X., et al.[2022]

In a prospective phase II trial involving 110 patients aged 70 and older with localized prostate cancer, stereotactic body radiotherapy (SBRT) demonstrated a severe toxicity rate of less than 5%, confirming its safety for this patient population.

The SBRT regimen resulted in a biochemical progression-free survival (bPFS) rate of 90% over a median follow-up of 36 months, indicating its efficacy in treating localized prostate cancer without negatively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective validation of stringent dose constraints for prostatic stereotactic radiation monotherapy: results of a single-arm phase II toxicity-oriented trial. Nguyen, P., Harzée, L., Retif, P., et al.[2022]

In a study of 515 patients treated with stereotactic body radiation therapy (SBRT) for prostate cancer, the 7-year freedom from biochemical failure rates were excellent, with 95.8% for low-risk, 89.3% for intermediate-risk, and 68.5% for high-risk patients, indicating strong disease control.

The treatment was found to be safe, with no acute Grade 3 or 4 complications and low rates of late toxicity (4% for rectal and 9.1% for urinary Grade 2 toxicity), while quality of life measures returned to baseline within 2 years post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of Life and Toxicity after SBRT for Organ-Confined Prostate Cancer, a 7-Year Study. Katz, AJ., Kang, J.[2022]

Androgen deprivation therapy is the most common treatment for radio-recurrent prostate cancer, but it is only palliative and can have adverse effects due to testosterone suppression.

Stereotactic body radiation therapy (SBRT) offers a promising alternative by delivering high doses to tumors with precision, potentially reducing damage to surrounding tissues, although current data supporting its use is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retreatment for prostate cancer with stereotactic body radiation therapy (SBRT): Feasible or foolhardy? Arcangeli, S., Agolli, L., Donato, V.[2020]

Stereotactic body radiotherapy (SBRT) shows a high local control rate of 98.1% in treating oligorecurrent prostate cancer limited to lymph nodes, based on a systematic review of 363 patients across nine studies with a median follow-up of 19.23 months.

The treatment demonstrated a low incidence of toxicity, with only 5.6% of patients experiencing grade ≥2 adverse effects, and no cases of grade 4 toxicity, suggesting that SBRT is a safe option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploring All Avenues for Radiotherapy in Oligorecurrent Prostate Cancer Disease Limited to Lymph Nodes: A Systematic Review of the Role of Stereotactic Body Radiotherapy. Ponti, E., Lancia, A., Ost, P., et al.[2022]

The study involving 12 patients with lymph node oligometastases demonstrated that hypofractionated radiotherapy using the 1.5T MR-linac system is feasible, with most pre-treatment plans meeting clinical dose criteria for different fractionation schemes.

However, the quality of treatment plans varied, with single fraction treatments (1x20 Gy) generally being of lesser quality compared to multiple fractions (5x7 Gy and 3x10 Gy), highlighting the importance of considering the target's location relative to critical structures when selecting a treatment plan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric feasibility of hypofractionation for SBRT treatment of lymph node oligometastases on the 1.5T MR-linac. Winkel, D., Werensteijn-Honingh, AM., Eppinga, WSC., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

GETUG-AFU 31: a phase I/II multicentre study evaluating the safety and efficacy of salvage stereotactic radiation in patients with intraprostatic tumour recurrence after external radiation therapy-study protocol. [2020]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Outcome of the first 200 patients with prostate cancer treated with MRI-Linac at Assuta MC. [2023]

3. Italy pubmed.ncbi.nlm.nih.gov

Adaptive SBRT by 1.5 T MR-linac for prostate cancer: On the accuracy of dose delivery in view of the prolonged session time. [2021]

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

Prostate stereotactic body radiotherapy—first UK experience. [2022]

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

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial. [2023]

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

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Short-Term Outcomes and Clinical Efficacy of Stereotactic Body Radiation Therapy (SBRT) for Oligometastases of Prostate Cancer in China. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Prospective validation of stringent dose constraints for prostatic stereotactic radiation monotherapy: results of a single-arm phase II toxicity-oriented trial. [2022]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Quality of Life and Toxicity after SBRT for Organ-Confined Prostate Cancer, a 7-Year Study. [2022]

10. Poland pubmed.ncbi.nlm.nih.gov

Retreatment for prostate cancer with stereotactic body radiation therapy (SBRT): Feasible or foolhardy? [2020]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Exploring All Avenues for Radiotherapy in Oligorecurrent Prostate Cancer Disease Limited to Lymph Nodes: A Systematic Review of the Role of Stereotactic Body Radiotherapy. [2022]

12. Ireland pubmed.ncbi.nlm.nih.gov

Dosimetric feasibility of hypofractionation for SBRT treatment of lymph node oligometastases on the 1.5T MR-linac. [2021]