Radiotherapy for High Risk Prostate Cancer

Not currently recruiting at 15 trial locations

Overseen By Ashley Feng, M.Sc.

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Sir Mortimer B. Davis - Jewish General Hospital

Must be taking: Androgen suppression

Must not be taking: Anti-arrhythmics

Disqualifiers: Other malignancies, Small-cell carcinoma, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 5

Duration: 28 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores improved radiation treatments for individuals with high-risk prostate cancer. It compares two methods: one combines standard pelvic radiation with a direct, temporary boost to the prostate (known as EBRT + HDR brachytherapy boost), while the other uses shorter, larger doses of radiation each day (referred to as Hypofractionated Dose Escalation Radiotherapy). The goal is to determine which approach is safer and more effective for this type of cancer. This trial may suit men recently diagnosed with high-risk prostate cancer who have not yet received certain cancer treatments. Participants must not have a history of other serious illnesses that could interfere with the treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in prostate cancer treatment.

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 patients must not have received any cytotoxic anticancer therapy for prostate cancer before joining. If you are taking a 5-alpha-reductase inhibitor for benign prostatic hypertrophy, it must be stopped before randomization.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both treatment options in this trial have been safe in previous studies. For external beam radiation therapy (EBRT) combined with a high-dose-rate brachytherapy (HDRB) boost, studies have found it effective with few side effects for patients with high-risk prostate cancer. One study highlighted its long-term benefits and limited side effects, making it a good option.

Regarding hypofractionated dose escalation radiotherapy, research indicates it is also well-tolerated. Studies have found no major differences in survival compared to traditional methods, and it has similar safety outcomes without an increase in side effects.

Both treatment options in this trial are supported by research showing they are generally safe and well-tolerated for patients with high-risk prostate cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for high-risk prostate cancer because they offer innovative approaches to radiation therapy. The hypofractionated dose escalation radiotherapy delivers a higher dose of radiation in fewer sessions compared to traditional methods, potentially reducing treatment time and increasing convenience for patients. Additionally, the combination of external beam radiotherapy (EBRT) with a high-dose-rate brachytherapy (HDRB) boost provides a targeted approach, which may enhance the effectiveness of the treatment by delivering concentrated radiation directly to the tumor. Both treatments are paired with androgen deprivation therapy (ADT) for a comprehensive approach to managing aggressive prostate cancer.

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

This trial compares two treatment approaches for high-risk prostate cancer. One arm involves hypofractionated dose escalation radiotherapy (HFRT) combined with androgen deprivation therapy (ADT). Studies have shown that HFRT matches the effectiveness of standard treatments for prostate cancer, with long-term data indicating fewer treatment failures over many years. The other arm combines external beam radiation therapy (EBRT) with a high-dose-rate brachytherapy boost (HDR-BT) alongside ADT. Research shows that this combination can lead to high survival rates, with studies reporting a 98.9% rate of patients without biochemical signs of cancer at five years. Both treatments have strong evidence supporting their effectiveness in managing high-risk prostate cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Dr. Tamim Niazi, MDCM

Principal Investigator

Jewish General Hospital, McGill University

Are You a Good Fit for This Trial?

Men with high risk prostate cancer diagnosed within the last 6 months, having a clinical stage of T3/T4, Gleason Score >8, or PSA >20. They must have no metastases on scans and can't have had previous chemotherapy for prostate cancer. Prior hormone therapy is allowed if started less than 28 days before joining. Men with severe heart failure, hip replacements, certain allergies or other serious health issues are excluded.

Inclusion Criteria

My prostate cancer is advanced with a high Gleason score or PSA level.

My recent scans showed no cancer in my pelvic or para-aortic lymph nodes.

My recent scans show no signs of cancer spread.

Exclusion Criteria

I have not had pelvic radiotherapy or have conditions like severe bladder issues.

I do not have any serious illness or condition that would prevent me from following the study's treatment plan.

You are allergic to any of the study medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either hypofractionated dose escalation radiotherapy or standard fractionation radiotherapy with HDR brachytherapy boost, along with 28 months of androgen deprivation therapy

28 months

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment, including digital rectal examination and evaluation of testosterone and PSA levels

13 years

Monthly for the first month, every 4 months for the first 2 years, every 6 months for the third year, then annually for 10 years

What Are the Treatments Tested in This Trial?

Interventions

• Androgen deprivation therapy
• EBRT + HDR brachytherapy boost
• Hypofractionated Dose Escalation Radiotherapy

Trial Overview

This trial compares two radiation treatments for high risk prostate cancer: standard pelvic external beam radiation plus HDR brachytherapy boost versus hypofractionated dose escalation radiotherapy. The study aims to determine which method is safer and more effective by randomly assigning participants to one of the two treatment plans.

How Is the Trial Designed?

Group I: ADT+EBRT+ HDR brachytherapy boost Experimental Treatment 2 Interventions

Standard fractionation radiotherapy: 46 Gy in 23 fractions (EBRT) and a 15-Gy HDRB boost in conjunction with 28 months of androgen deprivation therapy (ADT).

Group II: ADT+Hypofractionated Dose Escalation RT Active Control 2 Interventions

Hypofractionated dose escalation radiotherapy: 68 Gy in 25 fractions in conjunction with 28 months of androgen deprivation therapy (ADT).

Who Is Running the Clinical Trial?

Sir Mortimer B. Davis - Jewish General Hospital

Lead Sponsor

Trials

61

Recruited

25,800+

Published Research Related to This Trial

In a clinical trial involving 42 men with intermediate-risk prostate cancer, a treatment combining a single 15 Gy HDR brachytherapy boost with a five-fraction external beam radiation therapy (EBRT) resulted in a high biochemical disease-free survival rate of 95.5% after a median follow-up of 36 months.

The treatment demonstrated low toxicity, with only one case of acute Grade 3 gastrointestinal and genitourinary toxicity, and no significant differences in health-related quality of life across urinary, bowel, or sexual domains, suggesting it is a safe and effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IB clinical trial of 15 Gy HDR brachytherapy followed by hypofractionated/SBRT in the management of intermediate-risk prostate cancer. Den, RB., Greenspan, J., Doyle, LA., et al.[2023]

In a study of 101 patients with localized prostate cancer, high-dose rate brachytherapy (HDR) combined with external beam radiation (EBRT) showed promising early efficacy, with 82% of patients free from cancer recurrence after a median follow-up of 56 months.

While there were some significant acute toxicities, such as clot retention and a few serious complications, the long-term side effects were relatively low, with only 8% experiencing late grade 2 genitourinary toxicity and no late grade 3 gastrointestinal toxicity observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HDR brachytherapy combined with external beam radiation for localised prostate cancer: early experience from the Sydney Cancer Centre. Whalley, D., Patanjali, N., Jackson, M., et al.[2018]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12190164/

Long-Term Outcomes After High-Dose-Rate Brachytherapy ...

The 24-year outcomes support the viability and therapeutic efficacy of EBRT combined with a conformal HDR-BT boost for patients with VHR PCa.

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2452109425001484

High-dose-rate brachytherapy boost for prostate cancer: A ...

Overall, this study demonstrated the efficacy of EBRT-boosted brachytherapy in the treatment of intermediate- and high-risk prostate cancer, ...

3.

urotoday.com

urotoday.com/conference-highlights/astro-2024/astro-2024-prostate-cancer/155302-astro-2024-a-randomized-comparison-of-low-dose-rate-or-high-dose-rate-brachytherapy-combined-with-external-beam-radiation-for-unfavorable-intermediate-or-high-risk-prostate-cancer-efficacy-results-at-median-6-years.html

ASTRO 2024: A Randomized Comparison of Low Dose ...

HDR and LDR boost both appear to be highly effective for the treatment of unfavorable risk prostate cancer, with 85% biochemical cure (i.e., PSA ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8127662/

A comparative study of high-dose-rate brachytherapy boost ...

In patients with NCCN high-risk prostate cancer, HDR-BT boost had a significantly higher biochemical-free survival rate at 5 years (98.9% versus ...

5.

ascopost.com

ascopost.com/issues/march-25-2024/brachytherapy-boost-may-decrease-the-duration-of-androgen-deprivation-therapy-for-high-risk-prostate-cancer/

Brachytherapy Boost May Decrease the Duration of ...

Compelling data have demonstrated that achieving a BED2 of ≥ 200 Gy results in improved biochemical relapse–free survival, overall survival, and ...

6.

frontiersin.org

frontiersin.org/journals/urology/articles/10.3389/fruro.2025.1598726/full

High-dose-rate brachytherapy lowers travel burden for men ...

HDR-BT monotherapy significantly reduces the travel burden compared with EBRT for localized prostate cancer, with minimal treatment-associated toxicity.

7.

vvh.org

vvh.org/documents/Rossi-2025-Publication_High-Dose-Rate.HDR)-Brachytherapy-Boost.pdf

High-dose-rate (HDR) brachytherapy boost in combination ...

Intensified radiation therapy with extreme dose esca- lation, which can be safely achieved with combination. EBRT plus brachytherapy, can provide benefits in ...