MRI-Guided HDR Brachytherapy for Prostate Cancer

Overseen By Peter Chung, MD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must not be taking: Anticoagulants, Hormonal therapy

Disqualifiers: Metastases, Previous brachytherapy, 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

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat prostate cancer using MRI-guided high-dose-rate (HDR) brachytherapy, a form of targeted radiation therapy. It includes two groups: one for patients whose prostate cancer has returned after previous radiation treatment, and another for those with advanced prostate cancer who will receive this therapy alongside standard radiation. The trial aims to evaluate the effectiveness of this approach and gather data for future studies. It seeks men with recurrent prostate cancer after radiotherapy or high-risk localized prostate cancer planned for external beam radiation and HDR boost. As an unphased trial, this study offers patients the opportunity to contribute to pioneering research that could shape future prostate cancer treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that anti-coagulative therapy must be temporarily stopped during brachytherapy. If you are on active hormonal therapy, you cannot participate in Arm 1 of the trial.

What prior data suggests that this MRI-guided HDR brachytherapy technique is safe for prostate cancer patients?

Research has shown that high-dose-rate (HDR) brachytherapy, particularly when guided by MRI, holds promise for treating prostate cancer. This method delivers high doses of radiation directly to the tumor while protecting nearby healthy tissue, reducing the risk of harming surrounding organs.

Patients who have received HDR brachytherapy have generally tolerated it well. For example, one study found that this treatment provided good control over cancer and had fewer side effects compared to some other radiation methods. Another study showed that HDR brachytherapy alone yielded positive results for patients with intermediate-risk prostate cancer.

While all treatments carry potential risks, these studies suggest that HDR brachytherapy is generally safe with manageable side effects. As this is a pilot study, the researchers are also focusing on understanding the technical details and safety of this new procedure. Participants should discuss any concerns with their healthcare provider before deciding to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for prostate cancer, such as external beam radiotherapy (EBRT) and surgery, focus on removing or destroying the cancerous tissue through invasive or broad methods. However, MRI-guided HDR brachytherapy stands out because it allows for precise, targeted radiation directly to the tumor. Researchers are excited about this approach because it offers the potential to minimize damage to surrounding healthy tissues, which can lead to fewer side effects. Additionally, the use of MRI guidance enhances accuracy, making the treatment more effective for locally recurrent or advanced prostate cancer.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

Studies have shown promising results for using MRI-guided high-dose-rate (HDR) brachytherapy to treat prostate cancer. In this trial, one arm will focus on patients whose prostate cancer has returned in the same area, receiving tumor-targeted salvage HDR brachytherapy. Specifically, this treatment kept cancer markers low for about 54.4% of patients over three years, indicating stable cancer indicators for more than half of these patients during that time. Another arm will involve patients receiving HDR brachytherapy as a boost alongside external beam radiotherapy (EBRT). Research shows that this combination leads to better outcomes, with good overall survival and cancer-free progression rates. These findings suggest that using MRI to precisely target tumors can be effective, offering hope for patients needing advanced prostate cancer treatment. ^{5 6 7 8 9}

Who Is on the Research Team?

Peter Chung, MD

Principal Investigator

University Health Network, Princess Margaret Hospital

Are You a Good Fit for This Trial?

This trial is for men over 18 with prostate cancer. Arm 1 includes those who've had local recurrence after radiotherapy and a PSA doubling time over 6 months. Arm 2 targets patients with advanced prostate cancer needing an HDR brachytherapy boost during external beam radiotherapy. Participants must be in good physical condition (ECOG score of 0 or 1) and understand the study's risks.

Inclusion Criteria

My prostate cancer has come back.

I am older than 18 years.

Prior enrollment of UHN 05-0641-C or UHN 12-5015-C (Arm 1)

Exclusion Criteria

My cancer has spread to other parts of my body.

I weigh less than 136kg and do not have a pacemaker, metal implants, or shrapnel injuries.

Latex Allergy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

MRI-guided Prostate Biopsy

MRI-guided prostate biopsy performed prior to accrual to Arm 1

1 week

1 visit (in-person)

Treatment - Arm 1: Salvage HDR Brachytherapy

Patients with locally recurrent prostate cancer receive tumor-targeted salvage HDR brachytherapy

4 weeks

Multiple visits (in-person)

Treatment - Arm 2: Boost HDR Brachytherapy

Patients with locally advanced prostate cancer receive a boost of prostate-targeted HDR brachytherapy during external beam radiotherapy

Concurrent with EBRT

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• HDR Brachytherapy
• MRI Guided Needles

Trial Overview The trial tests MRI-guided needles delivering high-dose-rate (HDR) brachytherapy to treat prostate cancer, either as salvage therapy for recurrent cases post-radiotherapy (Arm 1), or as a targeted boost in conjunction with external beam radiotherapy for advanced cases (Arm 2).

How Is the Trial Designed?

Group I: 1: Salvage After EBRT Active Control 1 Intervention

Patients with locally recurrent prostate cancer after radiotherapy will receive tumor-targeted salvage HDR brachytherapy. Arm 1 of the study will be coordinated and closely integrated with a separate concurrent study of MRI-guided prostate biopsy, which will be performed prior to accrual to Arm 1 of this trial (UHN 05-0641-C).

Group II: 2: Boost to EBRT Active Control 1 Intervention

Patients with locally advanced prostate cancer will receive a boost of prostate-targeted HDR brachytherapy during external beam radiotherapy.

HDR Brachytherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as HDR Brachytherapy for:

• Localized prostate cancer
• Locally advanced prostate cancer
• Recurrent prostate cancer

Approved in United States as HDR Brachytherapy for:

• Prostate cancer
• Recurrent prostate cancer

Approved in Canada as HDR Brachytherapy for:

• Localized prostate cancer
• Locally advanced prostate cancer
• Recurrent prostate cancer

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Princess Margaret Hospital, Canada

Collaborator

Trials

121

Recruited

40,000+

Published Research Related to This Trial

In a phase II clinical trial involving 61 patients with intermediate- and high-risk prostate cancer, MRI-guided high-dose-rate brachytherapy (HDR-BT) combined with external beam radiotherapy was found to be safe, with only 30% experiencing acute grade 2 urinary toxicity and no severe (grade 4) toxicities reported.

While urinary quality of life scores initially declined at 1 month post-treatment, they returned to baseline levels by 3 months, although significant declines in bowel and sexual health scores were noted, with 44% to 57% of patients reporting clinically meaningful deterioration in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity and health-related quality of life outcomes of localized prostate cancer patients treated with magnetic resonance imaging-guided high-dose-rate brachytherapy: A prospective phase II trial. Sanmamed, N., Adleman, J., Berlin, A., et al.[2023]

High-dose rate brachytherapy (HDR-BT) using Ir-192 for prostate cancer patients at low risk of progression demonstrated a 100% disease-free survival rate over five years, indicating its efficacy as a monotherapy.

The treatment was safe, with only grade I toxic reactions reported in the genitourinary and gastrointestinal systems, and no severe adverse events, highlighting its potential to minimize harm to adjacent organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Brachytherapy as monotherapy for prostate cancer with the use of temporary sources]. Solodky, VA., Pavlov, AY., Panshin, GA., et al.[2019]

In a study of 164 men treated with high-dose-rate (HDR) brachytherapy for prostate cancer, the procedure showed a low incidence of genitourinary (GU) and gastrointestinal (GI) complications, indicating it is a safe treatment option.

With a median follow-up of 18.6 months, HDR brachytherapy resulted in a high overall survival rate of 98.7% and a disease-free survival rate of 96.2%, demonstrating its efficacy in treating localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building a High-Dose-Rate Prostate Brachytherapy Program With Real-Time Ultrasound-Based Planning: Initial Safety, Quality, and Outcome Results. Zhang, H., Kang, S., Ali, N., et al.[2022]

In a study of 122 patients treated with high-dose-rate prostate brachytherapy, both CT-based and MRI-based treatment planning resulted in similar rates of genitourinary (GU) and gastrointestinal (GI) toxicity, indicating that the choice of imaging modality does not significantly impact these side effects.

However, MRI-based planning showed a trend towards better recovery of erectile function over time, with a smaller decrease in sexual health scores at 18 months compared to CT planning, suggesting potential benefits in sexual quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Computed tomography versus magnetic resonance imaging in high-dose-rate prostate brachytherapy planning: The impact on patient-reported health-related quality of life. Harris, AA., Wu, M., Deirmenjian, JM., et al.[2022]

The study involved 77 patients with aggressive, nonmetastatic prostate cancer who underwent MRI-guided high-dose-rate brachytherapy (HDR-BT) after external radiotherapy, demonstrating that this treatment approach is feasible and well-tolerated with minimal severe acute toxicity.

After three years, the treatment showed promising outcomes with an 87.1% rate of biochemical disease-free survival and 100% disease-specific survival, indicating its potential effectiveness for high-risk prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated boost with high-dose-rate brachytherapy and open magnetic resonance imaging-guided implants for locally aggressive prostate cancer: a sequential dose-escalation pilot study. Ares, C., Popowski, Y., Pampallona, S., et al.[2022]

In a study of 88 patients with locally recurrent prostate cancer, MRI-guided salvage high dose rate brachytherapy (HDR-BT) showed promising cancer control, with 3-year and 5-year failure-free survival rates of 67% and 49%, respectively.

The focal technique (fBT) resulted in lower toxicity compared to the integrated boost technique (ibBT), although ibBT had a slightly higher rate of grade 2 side effects, suggesting that fBT may be more suitable for patients with lower PSA levels at the time of recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer. Ménard, C., Navarro-Domenech, I., Liu, ZA., et al.[2022]

The study developed a new HDR brachytherapy planning algorithm that optimizes catheter and isotope selection, potentially improving treatment outcomes for prostate cancer by better sparing the urethra and other organs at risk (OARs).

Results showed that while the Ir-192 only plans provided better OAR sparing, the Yb-169 plans achieved more uniform dose distribution to the clinical target volume (CTV), indicating that different isotopes can be strategically used to meet specific treatment goals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analytical HDR prostate brachytherapy planning with automatic catheter and isotope selection. Frank, CH., Ramesh, P., Lyu, Q., et al.[2023]

High-dose-rate (HDR) brachytherapy is a safe and effective treatment for low-risk prostate cancer, with 45% of patients experiencing some form of acute toxicity, primarily grade 1 urinary toxicity, within three months post-treatment.

The study found that urinary toxicity was significantly linked to the dose received by the urethra, with patients receiving over 111.3% of the prescribed dose being four times more likely to experience urinary issues, highlighting the importance of careful dose management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy delivered in two fractions as monotherapy for low-risk prostate cancer. Cendales, R., Alwers, E., Cifuentes, J., et al.[2020]

Prostate high dose rate (HDR) brachytherapy can be safely performed in a free-standing cancer center, with only 3.7% of procedures resulting in complications requiring catheter placement.

The treatment is well tolerated, with 20% of patients experiencing significant post-implant dysuria lasting an average of 7.5 days, indicating manageable side effects when combined with external beam radiation and hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate high dose rate brachytherapy in a free-standing cancer center setting. Tharp, M., Bennett, R., Burns, J., et al.[2016]

High-dose-rate (HDR) brachytherapy is an effective treatment for localized prostate cancer, allowing for precise dose delivery that improves patient outcomes and minimizes damage to surrounding healthy tissues.

The treatment exploits the unique characteristics of prostate cancer, such as its low α/β ratio, to enhance radiation sensitivity, making it a valuable option either alone or in combination with external beam therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HDR Prostate Brachytherapy. Crook, J., Marbán, M., Batchelar, D.[2020]

High-dose-rate (HDR) brachytherapy is a new and promising treatment for prostate cancer that offers potential benefits in radiation physics and radiobiology.

The article outlines the technique for using HDR brachytherapy as a standalone treatment, emphasizing its innovative approach, although clinical results are still developing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy as monotherapy for prostate cancer: technique, rationale and perspective. Yoshioka, Y., Suzuki, O., Otani, Y., et al.[2021]

MRI-guided high-dose-rate (HDR) brachytherapy for prostate cancer is a feasible and safe treatment option, with 9 patients treated successfully and no acute complications reported after 6 months.

The procedure is minimally invasive, requiring no general anesthesia or antibiotics, and effectively targets the tumor while sparing surrounding healthy tissue, leading to significant decreases in PSA levels and no residual cancer detected.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MRI targeted single fraction HDR Brachytherapy for localized Prostate Carcinoma: a feasibility study of focal radiation therapy (ProFocAL). Fischbach, F., Hass, P., Schindele, D., et al.[2023]

In a randomized phase II trial involving 170 patients with localized prostate cancer, HDR brachytherapy delivered in two fractions of 13.5 Gy resulted in significantly better 5-year biochemical disease-free survival (95%) compared to a single fraction of 19 Gy (73.5%).

The two-fraction treatment was well tolerated, with low rates of late rectal toxicity (1%) and manageable urinary toxicity (45% grade 2), indicating it is a safe and effective option for prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate high dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy. Morton, G., McGuffin, M., Chung, HT., et al.[2021]

In a study comparing pain management methods for men undergoing HDR brachytherapy for prostate cancer, those using patient controlled epidural analgesia (PCEA) reported significantly less pain than those using peripheral patient controlled analgesia (PCA).

The findings suggest that PCEA, which uses bupivacaine and fentanyl, is more effective for pain management during HDR brachytherapy, leading to improved patient satisfaction and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate HDR radiation therapy: a comparative study evaluating the effectiveness of pain management with peripheral PCA vs. PCEA. Colella, J., Scrofine, S., Galli, B., et al.[2013]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36091157/

MRI-guided focal or integrated boost high dose rate ... We report outcomes of a cohort enrolled across two institutions investigating MRI-guided tumor-targeted salvage high dose rate brachytherapy (HDR-BT).

2. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.971344/full

MRI-guided focal or integrated boost high dose rate ... We report a large series of MRI-guided, tumor-targeted HDR brachytherapy for locally recurrent prostate cancer. Overall, we found 3 and 5-year ...

3. advancesradonc.org advancesradonc.org/article/S2452-1094(25)00148-4/fulltext

High-Dose-Rate Brachytherapy Boost for Prostate Cancer Our study provides essential data on the clinical results of prostate brachytherapy in combination with EBRT. The rates of OS, MFS, and BPFS at 3 years are ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0167814025045955

Updated results of MR-assisted focal salvage HDR ... Our updated analysis of 59 patients undergoing focal salvage HDR brachytherapy showed a 36-month biochemical control rate of 54.4 % with encouragingly low ...

5. ajronline.org ajronline.org/doi/10.2214/AJR.10.5772

Locally Recurrent Prostate Cancer After High-Dose-Rate ... The purpose of this article is to retrospectively evaluate the utility of prostate MRI for detecting locally recurrent prostate cancer after high-dose-rate (HDR) ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6043748/

High dose-rate brachytherapy in the treatment of prostate cancer High dose-rate (HDR) brachytherapy involves delivery of a high dose of radiation to the cancer with great sparing of surrounding organs at risk.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425001484

High-dose-rate brachytherapy boost for prostate cancer: A ... An extended 12-year follow-up confirmed a 21% improvement in tumor control in the HDR-BT group. Furthermore, in comparison with a study ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2396328/

MRI-GUIDED HDR PROSTATE BRACHYTHERAPY IN ... Conclusion: High-dose-rate prostate brachytherapy in a standard 1.5T MRI scanner is feasible and achieves favorable dosimetry within a reasonable period with ...

9. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00651-0/fulltext

Prostate high dose-rate brachytherapy as monotherapy for ... Multi-fraction high dose-rate brachytherapy (HDR) has emerged as a safe and effective monotherapy for patients with intermediate-risk prostate ...