MR-Guided Radiotherapy for Prostate Cancer

(MRL-Boost Trial)

Overseen By Peter Chung, MD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Disqualifiers: Prior radiotherapy, Metastases, Ulcerative colitis, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: Up to 90 days

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness and feasibility of using MR-guided radiotherapy to target specific prostate cancer tumors identified by MRI scans. The treatment delivers a precise radiation boost to visible tumor areas either before or after the entire prostate gland receives standard radiation treatment. Men with localized prostate cancer, confirmed through biopsy and visible on MRI, may be suitable candidates, especially if they have a single risk factor such as tumor size or PSA level. Researchers will monitor participants for up to five years to assess how well this treatment manages their cancer. As an unphased trial, this study provides a unique opportunity to contribute to innovative research in prostate cancer treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that MR-guided radiotherapy is safe for prostate cancer treatment?

Research has shown that MR-guided radiotherapy is generally well-tolerated by prostate cancer patients, with studies reporting that severe side effects are rare. Most patients experience mild to moderate side effects, such as tiredness or urinary issues, which are common with radiation treatments. For example, one study found that patients had fewer side effects and reported a better quality of life due to the treatment's precise targeting.

Another study examined MR-Linac-guided stereotactic body radiotherapy, a type of precise radiation treatment, and found it safe for prostate cancer patients. The improved targeting of MR-guided radiotherapy allows doctors to focus more closely on the tumor, reducing exposure to surrounding healthy tissue and minimizing side effects.

In summary, MR-guided radiotherapy appears to be a safe option, with a lower risk of severe side effects compared to some other treatments. This precision helps keep patients more comfortable during and after treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about MR-guided radiotherapy for prostate cancer because it offers a more precise way to target tumors. Unlike traditional radiotherapy, which may affect both cancerous and healthy tissues, MR-guided radiotherapy uses advanced imaging to focus radiation specifically on the tumor. This precision reduces potential side effects and can lead to better outcomes for patients. Additionally, the ability to adjust treatment in real-time during the procedure allows for more effective and personalized cancer care.

What evidence suggests that MR-guided radiotherapy boost is effective for prostate cancer?

Research has shown that MR-guided radiotherapy can effectively treat prostate cancer. One study found that this treatment targets the tumor more precisely, potentially leading to fewer side effects, particularly those affecting the digestive system. Patients often report a good quality of life after receiving this treatment. Additionally, past patients experienced positive outcomes when MR-guided radiotherapy focused on visible tumors. Overall, evidence suggests this approach could be a promising option for those with localized prostate cancer.

In this trial, participants will receive an MR-guided tumor boost with SBRT, specifically targeting MRI-visible tumors. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for men with localized prostate cancer confirmed by tissue analysis and MRI, who are categorized as low to high-risk but ideally have only one high-risk factor. They must be planning external beam radiation therapy (possibly with hormone therapy), able to perform daily activities (ECOG 0 or 1), at least 18 years old, and can consent to the study. Men with severe bowel diseases, claustrophobia, metastases, certain genetic conditions or prior pelvic radiotherapy cannot join.

Inclusion Criteria

Ability to provide written informed consent to participate in the study

I am scheduled for external beam radiation therapy, with or without hormone therapy.

My prostate cancer diagnosis was confirmed through a tissue examination.

Exclusion Criteria

Contraindications to MRI including patients with pacemakers/implantable cardiac defibrillator, cerebral aneurysm clips, shrapnel injury

Severe claustrophobia

I have Ataxia Telangiectasia or Systemic Lupus Erythematosus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive MR-guided radiotherapy boost to MRI visible tumour before or after whole gland radiation

Up to 90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment, including acute and late toxicity, and quality of life assessments

5 years

Follow-up visits at 1, 3, 6 months, and annually up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• MR-guided Radiotherapy Boost

Trial Overview The study tests if giving an MR-guided radiotherapy boost directly to the tumor visible on MRI before or after whole gland radiation improves outcomes in prostate cancer patients. It's a single-arm feasibility study following participants for up to five years post-treatment.

How Is the Trial Designed?

Group I: MR-guided Tumour Boost with SBRT Experimental Treatment 1 Intervention

MR-guided radiotherapy boost to MRI visible tumour

MR-guided Radiotherapy Boost is already approved in European Union, United States for the following indications:

Approved in European Union as MR-guided Radiotherapy for:

• Localized prostate cancer

Approved in United States as MR-guided Radiotherapy for:

• Localized prostate cancer
• Intermediate-risk prostate cancer

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a study of 425 localized prostate cancer patients treated with MR-guided ultrahypofractionated radiation therapy, significant declines in prostate-specific antigen levels were observed, indicating effective treatment outcomes over 12 months.

While the therapy was generally safe, with peak toxicity reported at 3 months, patients not receiving androgen deprivation therapy experienced significant worsening of erectile function by 12 months, highlighting the need for patient education on potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-Guided Adaptive Radiation Therapy for Prostate Cancer: The First Results from the MOMENTUM study-An International Registry for the Evidence-Based Introduction of Magnetic Resonance-Guided Adaptive Radiation Therapy. Teunissen, FR., Willigenburg, T., Tree, AC., et al.[2023]

Reducing the planning target volume (PTV) margin in MR-guided radiotherapy (MRgRT) for low-risk prostate cancer patients led to significant dose reductions in organs-at-risk (OARs), particularly the bladder and rectum, while maintaining effective target coverage.

The study demonstrated that ultra-hypofractionated MR-guided RT using a 1.5 T MR-Linac is feasible and advantageous, as it allows for better soft tissue contrast and adaptive planning, resulting in lower radiation exposure to healthy tissues compared to conventional IMRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The impact of margin reduction on radiation dose distribution of ultra-hypofractionated prostate radiotherapy utilizing a 1.5-T MR-Linac. Onal, C., Efe, E., Bozca, R., et al.[2023]

The 1.5 T MRI-linear accelerator (LINAC) used for prostate cancer radiotherapy demonstrated high safety and efficacy, with a median gamma pass rate of 99.4% and no severe (≥grade 3) toxicities reported among 14 patients treated.

The treatment interruptions due to machine issues were low (2.9% of fractions), and the rate improved significantly after an upgrade, indicating that MRI-guided radiotherapy can be effectively integrated into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility of a 1.5 T magnetic resonance imaging-guided linear accelerator during conventionally fractionated and hypofractionated prostate cancer radiotherapy. Turkkan, G., Bilici, N., Sertel, H., et al.[2022]

In a phase 1 trial involving 22 prostate cancer patients, stereotactic MR-guided adaptive radiation therapy (SMART) demonstrated a low risk of acute urinary (22.7%) and gastrointestinal (4.5%) toxic effects, with no severe grade 3+ events reported.

Daily plan adaptation during SMART significantly improved dosimetry, ensuring that 100% of treatment plans were optimized to protect critical organs, highlighting the importance of real-time adjustments in radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-Guided Prostate Stereotactic Body Radiation Therapy With Daily Online Plan Adaptation: Results of a Prospective Phase 1 Trial and Supplemental Cohort. Leeman, JE., Cagney, DN., Mak, RH., et al.[2022]

Using MR-guided stereotactic body radiotherapy (SBRT) for prostate cancer showed that daily changes in patient anatomy had minimal impact on the radiation dose delivered, with prostate doses varying by only 0.5%.

The study analyzed data from four patients, indicating that the rectum and bladder also received minimal dose changes, mostly less than 0.5 Gy, which can inform strategies for daily online plan adaptation in MR-guided radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Online adaptive planning for prostate stereotactic body radiotherapy using a 1.5 Tesla magnetic resonance imaging-guided linear accelerator. Yang, J., Vedam, S., Lee, B., et al.[2021]

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 involved 78 men with localized prostate cancer who received intensity modulated radiotherapy (IMRT) with MRI-directed boosts, achieving high rates of biochemical control (92%) and local control (98%) over three years.

The treatment was well tolerated, with mostly mild toxicities; only 2 patients experienced severe side effects, which were manageable, indicating that this approach effectively targets cancer while minimizing harm to surrounding tissues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Outcome of Prostate Intensity Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Intra-Prostatic MRI Directed Boost. Schild, MH., Schild, SE., Wong, WW., et al.[2022]

A planning study involving 30 patients suggests that delivering a single 19 Gy dose to recurrent prostate cancer lesions using a 1.5 Tesla MR-Linac system is feasible, with target dose coverage achieved in 57% of MR-Linac plans compared to 47% for traditional FS-HDR-BT.

The MR-Linac system showed comparable effectiveness in dose coverage while potentially reducing exposure to surrounding organs at risk, indicating it could be a safer alternative to invasive FS-HDR-BT for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focal salvage treatment for radiorecurrent prostate cancer: A magnetic resonance-guided stereotactic body radiotherapy versus high-dose-rate brachytherapy planning study. Willigenburg, T., Beld, E., Hes, J., et al.[2022]

In a study of 51 localized prostate cancer patients treated with 1.5T MRgSBRT, the treatment demonstrated low rates of acute and subacute toxicities, with only 11.8% experiencing grade ≥ 2 acute genitourinary (GU) toxicities and 2.0% experiencing grade ≥ 2 acute gastrointestinal (GI) toxicities.

Patient-reported outcomes showed that while urinary, bowel, and hormonal scores decreased initially after treatment, they mostly returned to baseline levels over time, indicating that MRgSBRT is a safe option with manageable side effects for prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1.5T Magnetic Resonance-Guided Stereotactic Body Radiotherapy for Localized Prostate Cancer: Preliminary Clinical Results of Clinician- and Patient-Reported Outcomes. Poon, DMC., Yuan, J., Wong, OL., et al.[2021]

MRI-guided radiation therapy (RT) for localized prostate cancer shows promise, but the precise benefits compared to traditional CT-based guidance are still unclear, necessitating further investigation.

The review identified multiple ongoing trials and proposed eight clinical trial design strategies to explore the potential advantages of MRI guidance in improving treatment outcomes for prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive magnetic resonance image guided radiation for intact localized prostate cancer how to optimally test a rapidly emerging technology. Hall, WA., Kishan, AU., Hall, E., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8978250/

MR-guided radiotherapy for prostate cancer - PubMed Central This review summarises the potential and current evidence for MRI-guided radiotherapy, with a predominant focus on prostate cancer.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824000193

MRI-guided radiotherapy in twenty fractions for localised ... To our knowledge, this is the first paper which assesses the outcomes of moderately hypofractionated radiotherapy on a 1.5 T MR-Linac for prostate cancer.

3. redjournal.org redjournal.org/article/S0360-3016(24)00691-6/fulltext

Patient-Reported Outcomes Following Magnetic ... Patient-reported outcomes following magnetic resonance-guided radiation therapy for prostate cancer: a systematic review and meta-analysis.

4. elekta.com elekta.com/products/radiation-therapy/unity/prostate/

MR-guided RT for prostate cancer | MR-Linac The MIRAGE phase 3 randomized clinical trial demonstrated that MR-guided SBRT resulted in significantly reduced grade 2+ gastrointestinal and ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07142967

Trial Evaluating the Safety and Efficacy Of MR-Linac ... The primary aim is to evaluate the safety of delivering MR-Linac-guided stereotactic body radiotherapy (SBRT) after prior prostate external beam ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S240563082400048X

Stereotactic ultrahypofractionated MR-guided radiotherapy ... This study reports on acute toxicity rates and patient-reported outcomes after MR-guided adaptive ultrahypofractionated radiotherapy for localized prostate ...