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

Trial Summary

What is the purpose of this trial?

This is a single-arm feasibility study that is recruiting 40 patients with histologically-proven localized prostate cancer and MRI-defined lesion(s). Participants in this study will get MR-guided radiotherapy boost to MRI visible tumour before or after whole gland radiation. Participants will be followed-up as per standard of care schedule up to 5 years post-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 data supports the effectiveness of the treatment MR-guided Radiotherapy for Prostate Cancer?

Research shows that MR-guided radiotherapy for prostate cancer, using advanced imaging techniques like MR-Linac, can improve treatment precision and outcomes. Studies report positive 12-month outcomes and significant tumor regression in some cases, suggesting its potential effectiveness. ^{1 2 3 4 5}

Is MR-guided radiotherapy safe for humans?

Research shows that MR-guided radiotherapy for prostate cancer is generally safe, with most side effects being mild. In one study, only 2 out of 78 patients experienced more severe side effects, which improved over time. ^{2 6 7 8 9}

What makes MR-guided Radiotherapy Boost unique for treating prostate cancer?

MR-guided Radiotherapy Boost is unique because it uses magnetic resonance imaging (MRI) to precisely target prostate cancer, allowing for real-time adjustments during treatment. This approach offers better soft tissue contrast and the ability to adapt the radiation plan daily, potentially improving treatment accuracy and outcomes compared to traditional methods. ^{1 3 4 5 10}

Eligibility Criteria

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

I am 18 years old or older.

Ability to provide written informed consent to participate in the study

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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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]

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]

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]

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]

References

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

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

2. Switzerland 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. [2022]

3. United States 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. [2023]

4. United States 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. [2022]

5. Switzerland 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. [2021]

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

Early Outcome of Prostate Intensity Modulated Radiation Therapy (IMRT) Incorporating a Simultaneous Intra-Prostatic MRI Directed Boost. [2022]

7. Netherlands 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. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Online adaptive planning for prostate stereotactic body radiotherapy using a 1.5 Tesla magnetic resonance imaging-guided linear accelerator. [2021]

9. United States 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. [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Adaptive magnetic resonance image guided radiation for intact localized prostate cancer how to optimally test a rapidly emerging technology. [2022]