HDR Brachytherapy for Prostate Cancer

Overseen By Hiram A Gay, M.D.

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Washington University School of Medicine

Must be taking: Androgen deprivation

Must not be taking: Investigational agents

Disqualifiers: Other malignancy, Uncontrolled illness, 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: 1

Duration: 1 day

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to learn more about the outcomes and early and late side effects of treating early stage prostate cancer with high dose rate brachytherapy.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on androgen deprivation therapy, you may continue it as part of the trial.

What data supports the effectiveness of the treatment HDR brachytherapy for prostate cancer?

Research shows that HDR brachytherapy, often combined with external beam radiation, is effective in treating prostate cancer, with a high percentage of patients remaining disease-free and having good survival rates. Studies have demonstrated its safety and efficacy, especially in intermediate- and high-risk patients, and it has been shown to improve outcomes compared to external beam radiation alone. ^{1 2 3 4 5}

Is HDR brachytherapy generally safe for humans?

Research shows that HDR brachytherapy is generally safe for treating prostate cancer, with studies reporting only mild side effects like minor urinary and gastrointestinal issues. No severe adverse events were noted, indicating it is a safe treatment option. ^{6 7 8 9 10}

How is HDR brachytherapy different from other prostate cancer treatments?

HDR brachytherapy is unique because it delivers high doses of radiation directly to the prostate in a short period, minimizing exposure to surrounding healthy tissues. This method is particularly effective for prostate cancer due to the tumor's sensitivity to increased radiation doses, and it can be used alone or with other treatments like external beam radiation. ^{11 12 13 14 15}

Research Team

Hiram A Gay, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Men at least 18 years old with early stage prostate cancer, either low-risk or favorable intermediate-risk, may join this trial. They can have had hormone therapy within the last 6 months. Participants must be able to perform daily activities with minimal assistance and sign a consent form. Men who've had certain prior treatments or have serious health issues like heart disease, large TURP defects, or other recent cancers cannot participate.

Inclusion Criteria

My prostate cancer was confirmed through a biopsy.

My prostate cancer is classified as low-risk or favorable intermediate-risk.

I am 18 years old or older.

Exclusion Criteria

I cannot have general, spinal, or local anesthesia.

I had a prostate surgery that might affect the placement of an implant.

I do not have any uncontrolled illnesses like infections or heart problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single implant and single HDR fraction of either 21 Gy, 23 Gy, or 25 Gy within a 24-hour period

1 day

1 visit (in-person)

Follow-up

Participants are monitored for acute toxicity and biochemical control

3 months

Multiple visits (in-person)

Long-term follow-up

Participants are monitored for late toxicity and biochemical control

3 years

Treatment Details

Interventions

• HDR brachytherapy

Trial Overview This study tests different doses (21 Gy, 23 Gy, and 25 Gy) of high dose rate brachytherapy for treating early stage prostate cancer. Brachytherapy involves placing radioactive material inside the body to kill cancer cells.

Participant Groups

Group I: HDR brachytherapy - 25 Gy Experimental Treatment 1 Intervention

-All patients will be treated with a single implant and single HDR fraction. Treatment will be delivered within a single 24-hour period measured from the beginning of the implant procedure. All patients will receive a dose of 25 Gy.

Group II: HDR brachytherapy - 23 Gy Experimental Treatment 1 Intervention

-All patients will be treated with a single implant and single HDR fraction. Treatment will be delivered within a single 24-hour period measured from the beginning of the implant procedure. All patients will receive a dose of 23 Gy.

Group III: HDR brachytherapy - 21 Gy Experimental Treatment 1 Intervention

-All patients will be treated with a single implant and single HDR fraction. Treatment will be delivered within a single 24-hour period measured from the beginning of the implant procedure. All patients will receive a dose of 21 Gy.

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

Approved in European Union as High Dose Rate Brachytherapy for:

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

Approved in United States as High Dose Rate Brachytherapy for:

• Early-stage prostate cancer
• Intermediate-risk prostate cancer
• High-risk prostate cancer

Approved in Canada as High Dose Rate Brachytherapy for:

• Prostate cancer
• Recurrent prostate cancer

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Findings from Research

A new therapy protocol combining high dose rate (HDR) brachytherapy and external beam radiation showed promising results in treating localized prostate cancer, with a 76.7% survival rate and 86.3% of patients remaining disease-free over a median follow-up of 6 years.

The study found that factors like lower tumor stage (T1-2), lower grade (G1-2), and normal PSA levels after treatment were associated with longer survival, highlighting the importance of PSA status as an independent prognostic factor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[High dosage brachytherapy and external irradiation of localized prostate carcinoma--results at the Kiel University Clinic]. Kovács, G., Galalae, R., Loch, T., et al.[2018]

Patients with intermediate- to high-risk prostate cancer who received a high-dose-rate (HDR) brachytherapy boost along with 3D conformal radiotherapy (3DCRT) showed significantly better overall survival rates at 5, 10, and 15 years compared to those who received 3DCRT alone, with survival rates of 92%, 81%, and 67% versus 88%, 71%, and 53%, respectively.

The HDR boost group also demonstrated improved cause-specific survival rates, indicating that this treatment combination not only prolongs life but also effectively targets cancer progression, with cause-specific survival rates of 96%, 93%, and 87% for the HDR group compared to 95%, 88%, and 79% for the 3DCRT group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved survival for patients with prostate cancer receiving high-dose-rate brachytherapy boost to EBRT compared with EBRT alone. Kent, AR., Matheson, B., Millar, JL.[2019]

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]

In a study of 507 men with intermediate- and high-risk prostate cancer, HDR brachytherapy showed high long-term effectiveness, with biochemical no evidence of disease (bNED) rates of 86.9% at 10 years for intermediate-risk and 56.1% for high-risk patients.

The incidence of urethral stricture significantly decreased from 28.9% before 2005 to 4.2% after implementing prevention strategies, indicating improved safety of the procedure over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes of high-dose-rate brachytherapy for intermediate- and high-risk prostate cancer with a median follow-up of 10 years. Yaxley, JW., Lah, K., Yaxley, JP., et al.[2018]

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 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]

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]

High-dose-rate (HDR) brachytherapy for early-stage prostate cancer showed excellent outcomes, with a 100% biochemical progression-free survival rate and no severe toxicities (grade ≥3) reported among 39 patients followed for a median of 57 months.

While HDR treatment is generally safe, factors such as larger prostate size and higher doses to the urethra and bladder can lead to worse short-term urinary quality of life, and older patients may experience more significant sexual function impairment both shortly after treatment and in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient- and treatment-specific predictors of genitourinary function after high-dose-rate monotherapy for favorable prostate cancer. Raleigh, DR., Chang, AJ., Tomlin, B., 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]

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 (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 increasingly used for treating prostate cancer, allowing for large doses to be delivered directly to the tumor while minimizing damage to surrounding healthy tissues.

This technique is particularly effective for high-risk prostate cancer patients when combined with external beam radiotherapy, leveraging the unique sensitivity of prostate tumors to higher radiation doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HDR Brachytherapy in the Management of High-Risk Prostate Cancer. Masson, S., Persad, R., Bahl, A.[2021]

High Dose Rate Brachytherapy (HDR-BT) is effective for treating prostate cancer, initially used as a boost to external beam therapy but now also as a standalone treatment (HDR monotherapy).

The review highlights clinical outcomes and toxicity results from key studies, supporting the use of HDR-BT based on its favorable physical and radiobiological characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is high dose rate brachytherapy reliable and effective treatment for prostate cancer patients? A review of the literature. De Bari, B., Daidone, A., Alongi, F.[2018]

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 shows excellent biochemical control rates for localized prostate cancer, achieving 85-100% for low-risk, 81-100% for intermediate-risk, and 43-93% for high-risk cases, based on a comprehensive review of literature.

Severe toxicity from HDR brachytherapy is rare, with less than 5% of patients experiencing Grade 3 or higher side effects, highlighting its safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

American Brachytherapy Society consensus guidelines for high-dose-rate prostate brachytherapy. Yamada, Y., Rogers, L., Demanes, DJ., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[High dosage brachytherapy and external irradiation of localized prostate carcinoma--results at the Kiel University Clinic]. [2018]

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

Improved survival for patients with prostate cancer receiving high-dose-rate brachytherapy boost to EBRT compared with EBRT alone. [2019]

3. France pubmed.ncbi.nlm.nih.gov

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

4. England pubmed.ncbi.nlm.nih.gov

Long-term outcomes of high-dose-rate brachytherapy for intermediate- and high-risk prostate cancer with a median follow-up of 10 years. [2018]

5. 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]

6. 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]

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

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

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

Patient- and treatment-specific predictors of genitourinary function after high-dose-rate monotherapy for favorable 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. Poland pubmed.ncbi.nlm.nih.gov

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

11. Poland pubmed.ncbi.nlm.nih.gov

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

12. Egypt pubmed.ncbi.nlm.nih.gov

HDR Brachytherapy in the Management of High-Risk Prostate Cancer. [2021]

13. Netherlands pubmed.ncbi.nlm.nih.gov

Is high dose rate brachytherapy reliable and effective treatment for prostate cancer patients? A review of the literature. [2018]

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

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

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

American Brachytherapy Society consensus guidelines for high-dose-rate prostate brachytherapy. [2022]