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

Trial Summary

What is the purpose of this trial?

This pilot study initiates a research program testing the early technical and clinical performance of a novel procedure for MRI-guided high-dose-rate (HDR) prostate brachytherapy. Testing will proceed in two cohorts of patients. In Arm 1, 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). In arm 2, patients with locally advanced prostate cancer will receive a boost of prostate-targeted HDR brachytherapy during external beam radiotherapy. This technique will be prospectively evaluated in up to 100 patients. Preliminary data acquired in this pilot study will determine the technical limits of MRI guided HDR brachytherapy and will be critical for the judicious conduct of a subsequent phase II clinical trial. This proposal is innovative in two fundamental ways: MRI-guidance, and specific tumor targeting for HDR brachytherapy. Successful completion of this study will further individualize local therapy, not only for the benefit of the proportion of cancer patients for whom initial radiotherapeutic interventions have failed, but also provide valuable technical and clinical validation that these novel image-guided (IG) approaches are clinically feasible and could be applied more broadly in prostate cancer therapy.

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 data supports the effectiveness of the treatment MRI-Guided HDR Brachytherapy for Prostate Cancer?

Research shows that HDR brachytherapy, which is a type of internal radiotherapy, can precisely target prostate cancer with high doses of radiation while sparing healthy tissue, leading to fewer side effects. MRI-based planning in HDR brachytherapy improves visualization, potentially reducing treatment-related toxicity and improving patient-reported quality of life. ^{1 2 3 4 5}

Is MRI-guided HDR brachytherapy generally safe for humans?

Research shows that MRI-guided HDR brachytherapy is considered safe for treating prostate cancer, with studies reporting minimal side effects and no severe adverse events. It is effective in targeting cancer while minimizing harm to nearby organs. ^{6 7 8 9 10}

How is MRI-guided HDR brachytherapy different from other prostate cancer treatments?

MRI-guided HDR brachytherapy for prostate cancer is unique because it uses MRI imaging to precisely target the cancer, potentially reducing side effects and improving patient quality of life compared to traditional CT-based planning. This method allows for more accurate placement of radiation, which can be particularly beneficial for treating localized or aggressive tumors. ^{1 11 12 13 14}

Research Team

Peter Chung, MD

Principal Investigator

University Health Network, Princess Margaret Hospital

Eligibility Criteria

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

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)

Treatment Details

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).

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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 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]

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]

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]

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]

References

1. United States 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. [2022]

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

HDR Prostate Brachytherapy. [2020]

3. Ireland 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. [2021]

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

Prostate HDR radiation therapy: a comparative study evaluating the effectiveness of pain management with peripheral PCA vs. PCEA. [2013]

5. Poland pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy as monotherapy for prostate cancer: technique, rationale and perspective. [2021]

6. Poland pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy delivered in two fractions as monotherapy for low-risk prostate cancer. [2020]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Brachytherapy as monotherapy for prostate cancer with the use of temporary sources]. [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

MRI-guided focal or integrated boost high dose rate brachytherapy for recurrent prostate cancer. [2022]

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

Prostate high dose rate brachytherapy in a free-standing cancer center setting. [2016]

10. United States 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. [2022]

11. United States 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. [2023]

12. United States 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. [2022]

13. Germany pubmed.ncbi.nlm.nih.gov

MRI targeted single fraction HDR Brachytherapy for localized Prostate Carcinoma: a feasibility study of focal radiation therapy (ProFocAL). [2023]

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

Analytical HDR prostate brachytherapy planning with automatic catheter and isotope selection. [2023]