High-Dose Radiation Therapy for Prostate Cancer

Recruiting at 6 trial locations

Overseen By Victoria Brennan, MBBCH BAO

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Androgen deprivation therapy

Disqualifiers: Gleason score >7, PSA >20, Metastatic disease, MRI ineligibility, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

91 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating prostate cancer using MRI-guided high-dose radiation therapy. The researchers aim to determine if an additional radiation boost directly to the main tumor can lower the risk of cancer recurrence while minimizing side effects. Men with intermediate-risk prostate cancer, characterized by a PSA level between 10-20 ng/ml or a Gleason score of 7, may be suitable candidates for this study. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that MRI-guided High-dose Radiation Therapy is likely to be safe for humans?

Research has shown that MRI-guided radiation therapy (MRIgRT) for prostate cancer is promising in terms of safety. Studies have found that MRI helps doctors target the radiation more precisely at the prostate, reducing the risk of affecting nearby healthy tissue and leading to fewer side effects.

One study found that MRIgRT reduced long-term side effects and improved patients' overall quality of life. Another report showed that even two years after treatment, patients experienced acceptable levels of side effects.

Many who have undergone this treatment reported good results with fewer side effects, which is encouraging for those considering joining a trial like this. Although this trial uses a higher dose of radiation, the precision of MRI guidance could help keep side effects manageable. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about MRI-guided high-dose radiation therapy for prostate cancer because it offers a more precise and targeted treatment option compared to traditional radiation therapies. Unlike standard treatments that might affect surrounding healthy tissues, this method uses MRI technology to hone in on the cancerous area, potentially reducing side effects. Additionally, the ability to deliver high doses directly to the tumor could enhance effectiveness, offering hope for better outcomes in intermediate-risk prostate cancer patients.

What evidence suggests that MRI-guided High-dose Radiation Therapy might be an effective treatment for prostate cancer?

Research has shown that MRI-guided high-dose radiation therapy, which participants in this trial will receive, holds promise for treating prostate cancer. Studies have found that this method enhances the visibility of the prostate, enabling doctors to target radiation with greater precision. This precision can reduce the treatment area, potentially lowering the risk of side effects and improving patients' quality of life. Early results suggest that this approach might decrease the likelihood of cancer recurrence. By delivering a higher dose of radiation directly to the main tumor, there is hope that it may cure the cancer or prevent its return for a longer period. ^{1 2 3 6 7}

Who Is on the Research Team?

Victoria Brennan, MBBCH BAO

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

Men over 18 with intermediate-risk prostate cancer can join this trial. They should have a PSA level of 10-20 ng/ml, Gleason score equal to 7, and clinical stage T2b/T2c. Their prostate size must be ≤80 cc with a visible lesion on MRI that's at least 0.5 cm. They need to be in good health (KPS ≥80), have mild urinary symptoms (IPSS ≤15), and meet specific MRI criteria without severe claustrophobia or metal implants that affect the scan.

Inclusion Criteria

I can carry out normal activities with minimal symptoms.

My prostate is 80 cc or smaller.

My prostate cancer is at an intermediate stage with specific PSA, Gleason score, or clinical stage.

Exclusion Criteria

PSA >20

I have a history of inflammatory bowel disease.

MRI findings: >2 disease foci identifiable

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive SBRT with a boost dose to the main tumor and standard dose to the rest of the prostate

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• MRI-guided High-dose Radiation Therapy

Trial Overview This study tests if giving a high 'boost' dose of radiation directly to the main tumor along with standard doses to the rest of the prostate is more effective in treating intermediate-risk prostate cancer than current methods. The goal is longer-lasting prevention of cancer return with minimal side effects.

How Is the Trial Designed?

Group I: Prostate cancer patients Experimental Treatment 1 Intervention

Intermediate-risk prostate cancer patients will be eligible for this study. Risk groups will be assigned as per NCCN guidelines. Intermediate-risk patients will be defined as: * PSA 10-20 ng/ml or * Gleason score = 7 * Clinical stage T2b/T2c

MRI-guided High-dose Radiation Therapy is already approved in United States, European Union for the following indications:

Approved in United States as MRI-guided Radiation Therapy for:

• Prostate cancer

Approved in European Union as MRI-guided Radiation Therapy for:

• Prostate cancer

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

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 phase 3 randomized clinical trial involving 156 men with localized prostate cancer, MRI-guided stereotactic body radiotherapy (SBRT) significantly reduced the incidence of acute grade 2 or greater genitourinary toxic effects compared to CT guidance (24.4% vs 43.4%; P=0.01).

MRI guidance also led to fewer gastrointestinal toxic effects and better patient-reported outcomes, with a lower percentage of patients experiencing significant increases in urinary symptoms and decreases in bowel quality of life scores at 1 month post-treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance Imaging-Guided vs Computed Tomography-Guided Stereotactic Body Radiotherapy for Prostate Cancer: The MIRAGE Randomized Clinical Trial. Kishan, AU., Ma, TM., Lamb, JM., 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 involving 10 patients with liver metastases, MR-guided stereotactic body radiotherapy (MRgSBRT) demonstrated excellent visibility of tumors without the need for fiducial markers, indicating a promising non-invasive treatment option.

The treatment was well-accepted by patients, with no reported cases of symptomatic radiation-induced liver disease after a median follow-up of 10 months, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marker-less online MR-guided stereotactic body radiotherapy of liver metastases at a 1.5 T MR-Linac - Feasibility, workflow data and patient acceptance. Gani, C., Boeke, S., McNair, H., et al.[2022]

In a study of 3410 patients treated with SBRT for localized prostate cancer, only 4.75% received treatment planning using CT alone, and this group showed tolerable toxicity with only two cases of Grade 3+ toxicity reported.

Quality of life assessments indicated temporary declines in urinary and bowel function after treatment in the CT group, but these returned to baseline levels in follow-up, suggesting that CT-based planning is a safe alternative for patients who cannot undergo MRI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of stereotactic body radiation therapy for localized prostate cancer without treatment planning MRI. Amarell, K., Jaysing, A., Mendez, C., 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]

Prostate MRI is increasingly important in radiation therapy planning for prostate cancer, particularly in stereotactic body radiation therapy (SBRT), which delivers high doses of radiation in fewer sessions and is recognized as a valid treatment for various risk levels of prostate cancer.

MRI aids in reducing radiation exposure to sensitive areas like the urethra, thereby minimizing the risk of side effects, and helps in accurately targeting cancerous regions, which may enhance treatment effectiveness and improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate MRI in Stereotactic Body Radiation Treatment Planning and Delivery for Localized Prostate Cancer. Nigogosyan, Z., Ippolito, JE., Collins, SP., et al.[2022]

Stereotactic body radiation therapy (SBRT) using an MR-linac platform was successfully administered to 29 patients with minimal treatment delays, showing effective tumor response with most lesions either stable or reduced in size after treatment.

The use of MRI for real-time image guidance in SBRT resulted in lower liver doses and reduced toxicities, suggesting a safer treatment option for patients with hepatic tumors, although further studies are needed to fully assess the benefits and risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-time Magnetic Resonance-guided Liver Stereotactic Body Radiation Therapy: An Institutional Report Using a Magnetic Resonance-Linac System. Feldman, AM., Modh, A., Glide-Hurst, C., et al.[2023]

In a study involving 56 patients treated with Magnetic Resonance guided Radiotherapy (MRgRT) for primary liver tumors, no severe toxicities (greater than CTCAE grade 2) were observed, indicating a high safety profile for this treatment.

MRgRT achieved excellent local control rates of 98.1% at 12 months and 94.7% at 18 months, with an overall survival rate of 85.1% at 1 year, demonstrating its efficacy in managing primary liver tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A prospective registry study of stereotactic magnetic resonance guided radiotherapy (MRgRT) for primary liver tumors. Bordeau, K., Michalet, M., Dorion, V., et al.[2023]

The MIRAGE trial is a phase III randomized study involving 300 men with localized prostate cancer, comparing the safety and efficacy of MRI-guided versus CT-guided stereotactic body radiotherapy (SBRT) to determine which method results in lower acute genitourinary toxicity.

The primary goal is to assess the incidence of acute grade ≥2 genitourinary toxicity within the first 90 days post-treatment, with the hypothesis that MRI guidance will reduce toxicity compared to CT guidance, potentially leading to better patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging-guided stereotactic body radiotherapy for prostate cancer (mirage): a phase iii randomized trial. Ma, TM., Lamb, JM., Casado, M., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12384352/

MR-Guided Radiation Therapy for Prostate and Pancreas ... Magnetic resonance–guided radiation therapy (MRgRT) integrates MR imaging with precise radiation delivery, enabling improved soft-tissue ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10526919/

MRI-Guided Radiation Therapy for Prostate Cancer MRI-guided radiation therapy (MRIgRT) enables this precision-based approach by improving visualization of the prostate and the surrounding structures.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04997018

A Study of MRI-guided High-dose Radiation Therapy in ... One of the usual approaches to treating intermediate-risk prostate cancer is a type of radiation therapy called SBRT (stereotactic body radiation therapy).

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

Patient-Reported Outcomes Following Magnetic ... The improved accuracy of MRgRT enables safe reduction of treatment margins, potentially reducing toxicity and improving quality of life (QoL).

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

MRI-guided radiotherapy in twenty fractions for localised ... This study examines the potential clinical benefits of MRIgRT for men with localised prostate cancer, in the setting of moderately hypofractionated radiotherapy ...

6. advancesradonc.com advancesradonc.com/article/S2452-1094(24)00137-4/fulltext

Acute and Late Patient-Reported Toxicity Outcomes Our study is one the largest patient-reported outcomes study after prostate SMART. It shows acceptable levels of toxicity even up to 2 years after treatment.

7. uclahealth.org uclahealth.org/news/release/mri-guided-radiation-therapy-reduces-long-term-side-effects

MRI-guided radiation therapy reduces long-term side ... MRI-guided stereotactic body radiotherapy (SBRT) for prostate cancer significantly reduced long-term side effects and improved quality of life.