Radiotherapy for Prostate Cancer

(PROMPT Trial)

Recruiting at 3 trial locations

Overseen By Juanita Crook, MD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Must be taking: LHRH agonists, Anti-androgens

Disqualifiers: High metastatic burden, Abnormal liver function, others

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

Compensation: Varies

Number of Visits: 6

Duration: 4 weeks

168 Participants Needed

Trial Summary

What is the purpose of this trial?

We will investigate whether ultrahypofractionation using stereotactic ablative radiotherapy (SABR) or brachytherapy is as well-tolerated as moderately hypofractionated external beam radiotherapy (EBRT) for treating the prostate in patients with oligometastatic prostate cancer. Secondary aims include assessment of progression-free survival (PFS) and overall survival (OS) as well as cost-effectiveness. We hypothesize that ultrahypofractionation will maintain favorable toxicity profiles and quality of life while achieving comparable or better efficacy, thereby providing a convenient and cost-effective alternative to moderately hypofractionated EBRT.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that LHRH agonists or antagonists and anti-androgens must have started within a certain timeframe before randomization, suggesting that some medications related to prostate cancer treatment may need to be continued.

What data supports the effectiveness of this treatment for prostate cancer?

Research shows that high-dose-rate brachytherapy (HDR BRT) combined with external beam radiation therapy (EBRT) is effective for treating localized prostate cancer, with a 91% progression-free survival rate over three years. This combination is also associated with low complications and improved quality of life for patients. ^{1 2 3 4 5}

Is radiotherapy for prostate cancer generally safe for humans?

Research shows that high-dose-rate (HDR) brachytherapy, often used with external beam radiation therapy (EBRT), is generally safe for treating prostate cancer, with low complications reported in studies. ^{1 2 3 6 7}

How is the radiotherapy treatment for prostate cancer unique compared to other treatments?

This treatment combines high-dose-rate brachytherapy (a type of internal radiation) with external beam radiation therapy, which allows for a higher radiation dose to be delivered directly to the prostate, potentially improving outcomes while reducing treatment time. It is particularly beneficial for intermediate- and high-risk prostate cancer patients and can be easily implemented in facilities with brachytherapy capabilities. ^{1 2 3 8 9}

Research Team

Juanita Crook, MD

Principal Investigator

BCCancer

Eligibility Criteria

Men with newly diagnosed prostate cancer that has spread only a little (oligometastatic) can join. They should be planning long-term hormone therapy, in good health for treatment and follow-up, and have not had other prostate cancer treatments except hormone drugs started within the last 24 weeks.

Inclusion Criteria

My prostate cancer diagnosis was confirmed through a tissue examination.

I have only received hormone therapy for my prostate cancer.

I started hormone therapy for my cancer within the last 24 weeks.

Exclusion Criteria

I had a prostate surgery (TURP) within the last 12 weeks before brachytherapy.

My liver isn't working properly.

I cannot have external beam radiation due to conditions like inflammatory bowel disease or previous pelvic radiation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive one of the following treatments: standard moderately hypofractionated external radiotherapy, stereotactic body radiotherapy, high dose rate brachytherapy, or permanent seed implant brachytherapy

4 weeks

Multiple visits for treatment sessions

Follow-up

Participants are monitored for urinary quality of life and other secondary endpoints such as progression-free survival and overall survival

2 years

Assessments at 6 different points during the first 2 years

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

3 years

Treatment Details

Interventions

• High dose rate brachytherapy
• Hypofractionated external beam radiotherapy
• Permanent seed implant
• Stereotactic body radiotherapy

Trial Overview The trial is testing if using focused radiation (SABR or brachytherapy) is as safe and well-tolerated as standard external beam radiotherapy for treating oligometastatic prostate cancer. It also looks at survival rates and cost-effectiveness compared to the standard approach.

Participant Groups

Group I: Stereotactic body radiotherapy Experimental Treatment 1 Intervention

36.25 Gy is delivered to the prostate in 5 fractions given either weekly or every second day, using a SABR technique.

Group II: Permanent seed implant brachytherapy Experimental Treatment 1 Intervention

A single permanent implant of radioactive Iodine-125 seeds is performed under anesthesia as an out patient to deliver 125 Gy to the prostate

Group III: High dose rate brachytherapy Experimental Treatment 1 Intervention

A single fraction of 19 Gray (Gy) is delivered to the prostate under anesthesia as an out patient.

Group IV: standard Active Control 1 Intervention

External beam radiotherapy to deliver 5500 centiGray (cGy) in 20 fractions to the prostate over 4 weeks

High dose rate brachytherapy is already approved in European Union, United States, Canada, Japan 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:

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

Approved in Canada as HDR Brachytherapy for:

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

Approved in Japan as HDR Brachytherapy for:

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

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Findings from Research

High-dose-rate brachytherapy (HDR BRT) is gaining popularity as a treatment for prostate cancer, showing promise in both monotherapy and in combination with external beam radiation therapy (EBRT).

Long-term data indicates that HDR BRT provides effective oncologic outcomes while maintaining a manageable toxicity profile, supporting its use in various clinical scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy for prostate cancer: Rationale, current applications, and clinical outcome. Strouthos, I., Karagiannis, E., Zamboglou, N., et al.[2022]

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]

Combination high dose rate brachytherapy (HDRB) with external beam radiation therapy is a feasible and effective treatment for localized prostate cancer, showing a 91% prostate-specific antigen progression-free survival rate in 82 patients over a median follow-up of 3 years.

The use of HDRB allows for a shorter overall treatment time and is advantageous both biologically and logistically, making it a practical option for facilities that can perform brachytherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of localized prostate cancer using a combination of high dose rate Iridium-192 brachytherapy and external beam irradiation: initial Australian experience. Stevens, MJ., Stricker, PD., Saalfeld, J., et al.[2019]

The combination of high-dose-rate (HDR) brachytherapy and external beam radiotherapy (EBRT) resulted in an 86% biochemical control survival rate after 4 years for localized prostate cancer patients, indicating effective treatment outcomes, especially for lower-risk groups.

While the treatment was generally safe, 5% of patients experienced significant complications, including grade 3 urinary retention and chronic genitourinary toxicities, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy plus external beam radiotherapy for T1 to T3 prostate cancer: an experience in Taiwan. Chen, YC., Chuang, CK., Hsieh, ML., et al.[2007]

In a study of 90 men with high-risk prostate cancer treated with high-dose-rate brachytherapy (HDR-BT) after external beam radiation therapy (EBRT), patients reported better physical functioning and global health compared to reference data, although social, role, and cognitive functioning were worse.

The treatment resulted in low toxicity rates (10% gastrointestinal and 12.2% genitourinary adverse effects, all Grade I), indicating that HDR-BT combined with EBRT is effective with minimal adverse effects, and PSA levels may help predict health-related quality of life outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality of life and rates of toxicity after high-dose-rate brachytherapy in combination with external beam radiation therapy for high-risk prostate cancer. Huang-Tiel, HJ., Otto, I., Golka, K., et al.[2021]

High-dose-rate (HDR) brachytherapy as a standalone treatment for low- and intermediate-risk prostate cancer demonstrated excellent efficacy, with 10-year PSA progression-free survival rates of 97.8% and overall survival rates of 76.7% based on a study of 448 men over a median follow-up of 6.5 years.

The treatment was found to be safe, with no late grade 3 to 4 rectal toxicities reported and a low incidence (4.9%) of late grade 3 to 4 genitourinary toxicity, indicating a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results. Hauswald, H., Kamrava, MR., Fallon, JM., et al.[2022]

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]

In a study of 287 men with intermediate and high-risk prostate cancer, those treated with low dose rate external beam radiotherapy (LDR-EBRT) had a higher biochemical progression-free survival (bPFS) rate of 90.5% at 5 years compared to 77.6% for those treated with high dose rate external beam radiotherapy (HDR-EBRT).

Patients receiving HDR-EBRT were over twice as likely to experience biochemical progression compared to those receiving LDR-EBRT, indicating that LDR-EBRT may offer better long-term control of prostate-specific antigen (PSA) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of outcomes for patients with intermediate and high risk prostate cancer treated with low dose rate and high dose rate brachytherapy in combination with external beam radiotherapy. Slevin, F., Rodda, SL., Bownes, P., et al.[2022]

A systematic review of 40 studies found that combining external beam radiotherapy (EBRT) with high-dose rate (HDR) brachytherapy (EBTI) provides superior biochemical control and overall survival for prostate cancer patients.

Specifically, the risk of biochemical recurrence and overall survival was significantly better with EBTI compared to EBRT and EBSeeds, with hazard ratios indicating a 40% and 50% increased risk of recurrence and mortality, respectively, for EBRT compared to EBTI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: a systematic review. Pieters, BR., de Back, DZ., Koning, CC., et al.[2018]

References

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

High-dose-rate brachytherapy for prostate cancer: Rationale, current applications, and clinical outcome. [2022]

2. United States 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. [2023]

3. Australia pubmed.ncbi.nlm.nih.gov

Treatment of localized prostate cancer using a combination of high dose rate Iridium-192 brachytherapy and external beam irradiation: initial Australian experience. [2019]

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

High-dose-rate brachytherapy plus external beam radiotherapy for T1 to T3 prostate cancer: an experience in Taiwan. [2007]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Health-related quality of life and rates of toxicity after high-dose-rate brachytherapy in combination with external beam radiation therapy for high-risk prostate cancer. [2021]

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

High-Dose-Rate Monotherapy for Localized Prostate Cancer: 10-Year Results. [2022]

7. Australia pubmed.ncbi.nlm.nih.gov

HDR brachytherapy combined with external beam radiation for localised prostate cancer: early experience from the Sydney Cancer Centre. [2018]

8. Ireland pubmed.ncbi.nlm.nih.gov

A comparison of outcomes for patients with intermediate and high risk prostate cancer treated with low dose rate and high dose rate brachytherapy in combination with external beam radiotherapy. [2022]

9. Ireland pubmed.ncbi.nlm.nih.gov

Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: a systematic review. [2018]