Targeted Radiotherapy for Prostate Cancer

Overseen By Murtuza Saifuddin, M.S.

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Sunnybrook Health Sciences Centre

Disqualifiers: Inflammatory bowel disease, Hip replacement, others

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: 4

Duration: 5 fractions

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is a single centre feasibility trial. The trial will recruit men with intermediate risk localised prostate cancer who will all receive targeted dose (escalated/de-escalated dose directed by MRI) 5 fraction SBRT to the prostate. Trial Objectives are: 1. Primary To develop a 5 fraction de-escalated dose SBRT protocol capable of reducing side effects 2. Secondary * To assess levels of acute GU and GI toxicity (CTCAE) * To assess levels of late GU and GI toxicity (CTCAE) * To assess late sexual quality of life (expanded EPIC, IIEF-5) * To assess biochemical relapse-free survival at 2

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on androgen deprivation therapy (a treatment to lower male hormones), you may continue it for less than 6 months if your doctor agrees.

What data supports the effectiveness of the treatment MR Linac delivered Radiotherapy for prostate cancer?

Research shows that MR Linac radiotherapy for prostate cancer offers better visualization and tracking of the prostate during treatment, which can lead to fewer side effects and improved targeting of the cancer. Studies have found that this method reduces acute urinary side effects compared to traditional CT-guided radiotherapy, making it a promising option for patients. ^{1 2 3 4 5}

Is MR-Linac delivered radiotherapy safe for humans?

Research shows that MR-Linac delivered radiotherapy, used for prostate cancer, generally has a good safety profile with reduced rates of certain side effects compared to traditional methods. It offers advantages like better targeting of the cancer and sparing of healthy tissues, which can lead to fewer acute side effects. ^{1 2 3 5 6}

How is MR Linac delivered Radiotherapy different from other prostate cancer treatments?

MR Linac delivered Radiotherapy is unique because it combines MRI imaging with radiation delivery, allowing for better visualization and real-time tracking of the prostate and surrounding organs. This enables more precise targeting of the cancer, potentially reducing side effects and requiring fewer treatment sessions compared to traditional methods. ^{1 2 3 4 5}

Research Team

Danny Vesprini, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

Men aged 18 or older with intermediate risk localized prostate cancer, Gleason score between 3+3 and 4+3, MRI stage T2 or less. They must have a visible tumor on MRI that's less than half the size of the prostate and PSA <20 ng/ml. Short-term hormone therapy is allowed.

Inclusion Criteria

Your PSA level is less than 20 ng/ml before starting treatment.

My prostate tumor is visible on MRI and occupies less than half of my prostate.

My MRI shows a tumor with a grade 3 or higher rating.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 fraction SBRT to the prostate with dose variations based on mpMRI, PSA, and histology

5 fractions

Scans before and during radiotherapy on the MR-linac

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 4 and 12 weeks, and 6, 12, and 24 months

24 months

Assessments at 4 and 12 weeks, and 6, 12, and 24 months

Long-term follow-up

Participants are followed up for recurrence/biochemical failure as per standard care

Beyond 24 months

Treatment Details

Interventions

• MR Linac delivered Radiotherapy

Trial Overview The trial tests a new way to give radiotherapy for prostate cancer using an MR Linac machine. It aims to tailor the radiation dose specifically to each patient's tumor, potentially reducing side effects by either increasing or decreasing the dose as needed.

Participant Groups

Group I: Interventional Experimental Treatment 1 Intervention

All radiotherapy will be delivered on the MR-linac

MR Linac delivered Radiotherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Stereotactic Body Radiation Therapy (SBRT) for:

• Localized prostate cancer
• Intermediate-risk prostate cancer
• High-risk prostate cancer

Approved in United States as Stereotactic Body Radiation Therapy (SBRT) for:

• Localized prostate cancer
• Intermediate-risk prostate cancer
• High-risk prostate cancer

Approved in Canada as Stereotactic Body Radiation Therapy (SBRT) for:

• Localized prostate cancer
• Intermediate-risk prostate cancer
• High-risk prostate cancer

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Findings from Research

In a study of 135 patients with prostate cancer, stereotactic body radiotherapy (SBRT) using 1.5-T MR-guided radiotherapy (MRgRT) was found to be feasible and safe, with similar rates of acute toxicity compared to conventional volumetric modulated arc therapy (VMAT).

While there was no significant difference in overall acute toxicity between MR-linac and conventional linac, MRgRT showed a potential trend towards reduced grade 2 gastrointestinal toxicity, suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Linac-based versus MR-guided SBRT for localized prostate cancer: a comparative evaluation of acute tolerability. Nicosia, L., Mazzola, R., Rigo, M., et al.[2023]

The use of MR-guided stereotactic body radiation therapy (SBRT) for prostate cancer has shown promising results in reducing acute genitourinary (GU) toxicities, making it a safer option compared to traditional CT-guided methods, as demonstrated in the MIRAGE trial.

A new phase II trial is underway to compare the efficacy and toxicity of delivering MR-guided SBRT in 2 fractions versus 5 fractions, with 136 men participating, aiming to determine if fewer treatment sessions can maintain similar safety profiles over a 2-year period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase II trial of MR-guided prostate stereotactic body radiotherapy administered in 5 or 2 fractions for localized prostate cancer (FORT). Wolfe, S., Diven, MA., Marciscano, AE., et al.[2023]

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]

The use of a magnetic resonance linear accelerator (MR-Linac) for adaptive radiation therapy allowed for precise targeting and significant inter-fraction tumor regression in a patient with advanced prostate cancer, with a notable 49% reduction in tumor volume during treatment.

The patient experienced improved urinary symptoms and pain relief, highlighting the efficacy and safety of MR-guided adaptive radiation therapy in delivering high-dose palliative treatment while minimizing radiation exposure to surrounding healthy tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: MR-Guided Adaptive Radiotherapy, Some Room to Maneuver. Li, W., Winter, J., Padayachee, J., et al.[2022]

The study demonstrated the feasibility of using a 1.5 T MRI-linear accelerator (MR-Linac) for salvage radiotherapy (SRT) in 16 prostate cancer patients, with a high success rate of 94.6% for treatment fractions and no patient-sided treatment failures.

Patients reported high tolerability of the treatment, with low rates of acute toxicity observed during and three months after radiotherapy, indicating that this method is safe and well-suited for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First Experience and Prospective Evaluation on Feasibility and Acute Toxicity of Online Adaptive Radiotherapy of the Prostate Bed as Salvage Treatment in Patients with Biochemically Recurrent Prostate Cancer on a 1.5T MR-Linac. Wegener, D., Thome, A., Paulsen, F., et al.[2022]

A meta-analysis of 29 studies involving 2547 patients found that MRg-A-SBRT significantly reduces the risk of acute grade 2 or higher genitourinary (GU) toxicity by 44% and gastrointestinal (GI) toxicity by 60% compared to CT-SBRT.

MRg-A-SBRT offers a safer alternative for prostate cancer treatment by minimizing short-term side effects, although further research is needed to assess long-term toxicity and disease control outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity comparison of magnetic resonance-guided adaptive versus fiducial or computed tomography-guided non-adaptive prostate stereotactic body radiotherapy: A systematic review and meta-analysis. Leeman, JE., Shin, KY., Chen, YH., et al.[2023]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Linac-based versus MR-guided SBRT for localized prostate cancer: a comparative evaluation of acute tolerability. [2023]

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

A randomized phase II trial of MR-guided prostate stereotactic body radiotherapy administered in 5 or 2 fractions for localized prostate cancer (FORT). [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: MR-Guided Adaptive Radiotherapy, Some Room to Maneuver. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

First Experience and Prospective Evaluation on Feasibility and Acute Toxicity of Online Adaptive Radiotherapy of the Prostate Bed as Salvage Treatment in Patients with Biochemically Recurrent Prostate Cancer on a 1.5T MR-Linac. [2022]

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

Acute toxicity comparison of magnetic resonance-guided adaptive versus fiducial or computed tomography-guided non-adaptive prostate stereotactic body radiotherapy: A systematic review and meta-analysis. [2023]