Ultra-Hypofractionated Radiotherapy + Brachytherapy for Prostate Cancer

(HYPO-5 Trial)

Overseen By Josee Allard

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: CHU de Quebec-Universite Laval

Must not be taking: Alpha-blockers

Disqualifiers: T3 or T4 stage, N1, M1, PSA > 20, Gleason 8-10, others

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

Compensation: Varies

Number of Visits: 5

205 Participants Needed

Trial Summary

What is the purpose of this trial?

Phase 1-2 study, comparing ultra-hypofractionnated (UH) to a moderately hypofractionnated (MH) radiation therapy, with image guided HDR prostate brachytherapy. Using iso-equivalent doses, a non-inferiority analysis will be done in order to prove UH non-inferior to MH, toxicity wise. Acceptability, tolerability, acute and late toxicity will be reported. MRI visible dominant intra-prostatic lesion will be outlines and variability between radiation oncologists and radiologists will be reported. As secondary objective, biochemical and clinical failure free survival will be reported at 5 \& 10 years.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are taking alpha-blocking medication and have an IPSS Score over 20, you may not be eligible for the trial.

What data supports the effectiveness of the treatment Ultra-Hypofractionated Radiotherapy + Brachytherapy for Prostate Cancer?

Research shows that high-dose-rate (HDR) brachytherapy, when used as a boost with external beam radiotherapy, has a high degree of effectiveness and low long-term side effects for prostate cancer. Studies report relapse-free survival rates of over 90% for intermediate-risk patients, making it a strong treatment option. ^{1 2 3 4 5}

Is Ultra-Hypofractionated Radiotherapy + Brachytherapy safe for humans?

Research shows that high-dose-rate (HDR) brachytherapy, often used with external beam radiation therapy, has been found to be safe in treating prostate cancer, with studies reporting an excellent toxicity profile and positive clinical outcomes. ^{1 2 4 6 7}

What makes the Ultra-Hypofractionated Radiotherapy + Brachytherapy treatment unique for prostate cancer?

This treatment is unique because it combines ultra-hypofractionated radiotherapy (very high doses in fewer sessions) with high-dose-rate brachytherapy (internal radiation), potentially allowing for effective prostate cancer treatment in fewer sessions compared to traditional methods. This approach aims to maximize tumor cell killing while minimizing damage to surrounding healthy tissue. ^{4 5 8 9 10}

Research Team

Andre-Guy Martin

Principal Investigator

CHU de Québec

Eligibility Criteria

Men with early-stage prostate cancer (Stage T1c or T2), no spread to lymph nodes or distant organs, PSA levels below 20ng/ml, and a Gleason Score of 6 or 7. Participants must be able to give written consent. Excluded are those with advanced disease stages, high Gleason Scores (8-10), severe urinary symptoms, prior pelvic radiotherapy, bilateral hip prosthesis, under age 18, inflammatory bowel disease history, or active collagen diseases.

Inclusion Criteria

My cancer has not spread to distant parts of my body.

My prostate cancer has a Gleason score of 6 or 7.

PSA < 20ng/ml

Exclusion Criteria

I have had radiation therapy to my pelvic area before.

I have a history of autoimmune diseases like Lupus.

I have a history of inflammatory bowel disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Brachytherapy

Participants undergo brachytherapy with implantation under anesthesia, followed by dosimetric optimization and dose delivery

1 week

Multiple visits for implantation and monitoring

Radiotherapy

Participants receive radiotherapy via IMRT, VMAT, or SBRT techniques, with a dose of 25 Gy in 5 fractions over 7 days

1 week

5 visits (in-person)

Follow-up

Participants are monitored for toxicity and quality of life outcomes, with assessments at 3, 6, 12 months, and yearly up to 5 years

5 years

Regular follow-up visits as needed

Treatment Details

Interventions

• HDR Brachytherapy Boost
• Moderately Hypofractionnated Radiotherapy
• Ultra Hypofractionnated Radiotherapy

Trial Overview This Phase 1-2 study compares two types of radiation therapy for prostate cancer: ultra-hypofractionnated versus moderately hypofractionnated therapy combined with image-guided HDR brachytherapy. The goal is to determine if the shorter treatment is just as safe as the longer one in terms of side effects over time.

Participant Groups

Group I: ultra hypo fractionation radiation therapy Experimental Treatment 1 Intervention

comparative PRO's of 25 Gy in 5 daily fractions (Ultra hypo fractionation) administered to prostate and 1st centimeter of proximal seminal vesicle, starting mid week and ending mid following week.

Group II: moderate hypo fractionation radiation therapy Active Control 1 Intervention

PRO's of moderate hypo fractionation, 37,5 Gy in 15 or 36 Gy in 12 daily fractions administered 5 days per week.

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

Approved in European Union as HDR Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Uterine cancer
• Vaginal cancer
• Rectal cancer
• Esophageal cancer
• Lung cancer
• Breast cancer
• Skin cancer

Approved in United States as HDR Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Uterine cancer
• Vaginal cancer
• Rectal cancer
• Esophageal cancer
• Lung cancer
• Breast cancer
• Skin cancer

Approved in Canada as HDR Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Uterine cancer
• Vaginal cancer
• Rectal cancer
• Esophageal cancer
• Lung cancer
• Breast cancer
• Skin cancer

Approved in Japan as HDR Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Uterine cancer
• Vaginal cancer
• Rectal cancer
• Esophageal cancer
• Lung cancer
• Breast cancer
• Skin cancer

Who Is Running the Clinical Trial?

CHU de Quebec-Universite Laval

Lead Sponsor

Trials

177

Recruited

110,000+

Findings from Research

In a study of 148 prostate cancer patients treated with high-dose-rate (HDR) brachytherapy followed by intensity-modulated radiation therapy (IMRT), the treatment showed a high 4-year biochemical disease-free survival (bDFS) rate of 96.8% using the Phoenix criteria.

The treatment was well tolerated, with low rates of genitourinary (10%) and gastrointestinal (5%) toxicities, indicating that this combination therapy is both effective and safe for patients in a community setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four-year outcomes of hypofractionated high-dose-rate prostate brachytherapy and external beam radiotherapy. Chen, WC., Tokita, KM., Ravera, J., et al.[2018]

High dose rate (HDR) brachytherapy combined with external beam radiation therapy has been shown to be a safe and effective treatment for intermediate and high-risk prostate cancer, leading to a significant increase in treatment options and outcomes.

The success of HDR brachytherapy has prompted its use as a standalone treatment for low to intermediate-risk prostate cancer, supported by excellent toxicity profiles and clinical results from ongoing research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of high dose rate brachytherapy in the treatment of prostate cancer. Ghilezan, M.[2012]

High-dose-rate brachytherapy (HDR) combined with external beam radiotherapy shows high efficacy in treating prostate cancer, with relapse-free survival rates exceeding 90% for intermediate-risk patients and over 80% for high-risk patients, outperforming external beam radiotherapy alone.

A specific regimen of a single 15 Gy HDR boost along with 37.5 Gy of hypofractionated radiotherapy is well tolerated and can be completed in under 90 minutes, making it a quick and efficient treatment option for men with high and intermediate risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy boost for prostate cancer: rationale and technique. Morton, GC.[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]

High-dose-rate brachytherapy (HDR-BT) delivers a significantly higher dose to the planning target volume (PTV) compared to both robotic and conventional stereotactic body radiotherapy (SBRT), indicating its potential for more effective treatment of prostate cancer.

HDR-BT results in lower radiation exposure to the bladder and rectum than SBRT, which may reduce the risk of side effects, although it does expose the urethra to a higher dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment planning comparison of high-dose-rate brachytherapy vs. robotic and conventional stereotactic body radiotherapy for ultrahypofractionated treatment of prostate cancer. Yoshioka, Y., Sasamura, K., Ito, M., et al.[2023]

A retrospective analysis of 214 prostate cancer patients treated with high dose rate brachytherapy (HDR-BT) combined with external beam radiotherapy showed an overall 5-year biochemical no evidence of disease (bNED) rate of 82%, indicating effective treatment outcomes.

The study found that HDR-BT is safe, with few severe late complications, primarily urethral stricture in 13 patients, and no severe rectal complications, supporting its use for dose escalation in localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of high dose rate brachytherapy in radiotherapy of localised prostate cancer. Aström, L., Pedersen, D., Mercke, C., et al.[2005]

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]

Extreme hypofractionation, which involves delivering large doses of radiation in fewer sessions, may be particularly effective for prostate cancer due to the tumor's low sensitivity to radiation and high ability to repair damage.

Both high-dose rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are promising methods for this approach, but further research is needed to ensure effective dose distribution and minimize treatment duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy for prostate cancer: treatment approaches and clinical outcomes. Miralbell, R.[2020]

The ultra-hypofractionated (UHF) radiation therapy regimen combined with HDR brachytherapy boost showed no significant differences in gastrointestinal or genitourinary side effects compared to moderate-hypofractionated regimens, indicating similar safety profiles.

No biochemical recurrences were observed in the UHF treatment group over a median follow-up of 48.5 months, suggesting effective local control of prostate cancer comparable to standard treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of four-year toxicities and local control of ultra-hypofractionated vs moderate-hypofractionated image guided prostate radiation with HDR brachytherapy boost: A phase I-II single institution trial. Beaudry, MM., Carignan, D., Foster, W., et al.[2023]

Ultrahypofractionated radiotherapy, which involves delivering treatment in five to seven fractions, is becoming a standard practice for localized prostate cancer, showing promise for even fewer fractions.

Evidence suggests that localized prostate cancer can be safely and effectively treated in fewer than five fractions using techniques like high dose rate brachytherapy or stereotactic body radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrahypofractionated Radiotherapy for Localised Prostate Cancer: How Far Can We Go? Corkum, MT., Achard, V., Morton, G., et al.[2022]

References

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

Four-year outcomes of hypofractionated high-dose-rate prostate brachytherapy and external beam radiotherapy. [2018]

2. France pubmed.ncbi.nlm.nih.gov

Role of high dose rate brachytherapy in the treatment of prostate cancer. [2012]

3. Poland pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy boost for prostate cancer: rationale and technique. [2022]

4. 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]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Treatment planning comparison of high-dose-rate brachytherapy vs. robotic and conventional stereotactic body radiotherapy for ultrahypofractionated treatment of prostate cancer. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Long-term outcome of high dose rate brachytherapy in radiotherapy of localised prostate cancer. [2005]

7. 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]

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

Stereotactic body radiotherapy for prostate cancer: treatment approaches and clinical outcomes. [2020]

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

Comparison of four-year toxicities and local control of ultra-hypofractionated vs moderate-hypofractionated image guided prostate radiation with HDR brachytherapy boost: A phase I-II single institution trial. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Ultrahypofractionated Radiotherapy for Localised Prostate Cancer: How Far Can We Go? [2022]