EBRT + ADT + HDR Brachytherapy for Prostate Cancer

(Prostate005 Trial)

Overseen By Song W

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Virginia

Must be taking: Androgen deprivation

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: Bone metastases, Prior invasive malignancy, others

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

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

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a combination of treatments can reduce side effects and improve outcomes for prostate cancer patients. It includes androgen deprivation therapy (hormone therapy to lower testosterone), high-dose internal radiation (HDR brachytherapy), and external beam radiation (EBRT). The study focuses on the impact of these treatments on quality of life and survival rates. Men with high-risk prostate cancer who have not undergone previous prostate surgery or radiation may be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that hormone therapy, known as androgen deprivation therapy (ADT), is generally well-tolerated by prostate cancer patients. Over 90% of patients respond positively, with 80% to 90% experiencing significant tumor shrinkage. However, some may experience fatigue or weaker bones as side effects.

Studies have indicated that external beam radiation therapy (EBRT) is usually safe for treating prostate cancer. Patients often achieve good results, and it has been proven safe over many years. Common side effects might include temporary bladder or bowel problems.

Initial findings suggest that high-dose-rate (HDR) brachytherapy is also a safe option for prostate cancer. It effectively controls the disease and is widely used as a standard treatment. Some patients might experience mild discomfort or urinary symptoms.

Overall, each component of the trial treatment has demonstrated promising safety records in previous studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Androgen Deprivation Therapy (ADT), External Beam Radiation Therapy (EBRT), and High-Dose-Rate (HDR) Brachytherapy for prostate cancer because it offers a potentially more effective approach than current standard treatments like surgery, EBRT alone, or low-dose-rate brachytherapy. This combination targets prostate cancer in multiple ways: ADT reduces hormone levels that fuel cancer growth, EBRT delivers precise radiation from outside the body, and HDR Brachytherapy places high doses of radiation directly inside the prostate. The synergy of these methods could lead to better control of the cancer, fewer side effects, and improved patient outcomes compared to using them individually.

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

Research has shown that using both external beam radiation therapy (EBRT) and brachytherapy can help control prostate cancer for longer periods. One study found that patients who received EBRT had a 5-year survival rate of 74.4% and a prostate cancer-specific survival rate of 89.1%. Another review indicated that adding brachytherapy to radiation therapy can extend cancer control, although it might increase urinary side effects. In this trial, participants will receive a combination of EBRT, HDR brachytherapy, and androgen deprivation therapy (ADT). While specific data on combining these treatments with ADT is not included here, ADT is known to enhance the effectiveness of radiation therapy by lowering male hormone levels that prostate cancer cells need to grow. This combination aims to improve survival and control cancer while managing side effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Chris Luminais, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for men over 18 with a specific diagnosis of prostate cancer that's considered unfavorable-intermediate, high, or very high-risk. They should have an ECOG performance status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but can do light work. Participants must not have had certain previous treatments like pelvic irradiation and should not be suffering from severe health conditions such as unstable heart disease.

Inclusion Criteria

Provision of signed and dated informed consent form.

I was diagnosed with prostate cancer within the last year.

Pelvic MRI obtained up to 12 months before registration.

Exclusion Criteria

I do not have severe liver problems or jaundice.

I am currently on IV antibiotics for a bacterial or fungal infection.

I haven't been hospitalized for heart issues like unstable angina or heart failure in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Androgen Deprivation Therapy (ADT)

Participants receive androgen deprivation therapy as part of the treatment regimen

2-3 months

External Beam Radiation Therapy (EBRT)

Participants undergo external beam radiation therapy

5-8 weeks

High Dose-rate Brachytherapy

Participants receive MRI-guided high dose-rate brachytherapy

1-2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Androgen Deprivation Therapy
• External Beam Radiation
• HDR Brachytherapy

Trial Overview The study tests if combining Androgen deprivation therapy (ADT), MRI-guided HDR brachytherapy (internal radiation), and external beam radiation therapy (EBRT) reduces side effects while improving patient outcomes and survival rates. It examines the quality of life after receiving these combined treatments for prostate cancer.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 3 Interventions

Androgen Deprivation Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Recurrent prostate cancer

Approved in United States as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Recurrent prostate cancer
• Localized prostate cancer

Approved in Canada as Androgen Deprivation Therapy for:

• Prostate cancer
• Metastatic prostate cancer
• Recurrent prostate cancer
• Localized prostate cancer

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

Patients with unfavorable intermediate- and high-risk prostate cancer who received extreme dose escalation with a combination of external beam radiotherapy (EBRT) and brachytherapy were significantly less likely to receive androgen deprivation therapy (ADT), with an odds ratio of 0.67, indicating a notable decrease in ADT utilization.

The study suggests a potential underutilization of ADT in higher-risk patients undergoing combined radiation treatments, highlighting the need for further prospective studies to clarify the role of ADT in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variations in patterns of concurrent androgen deprivation therapy use based on dose escalation with external beam radiotherapy vs. brachytherapy boost for prostate cancer. Mohiuddin, JJ., Narayan, V., Venigalla, S., et al.[2019]

In a study of 392 prostate cancer patients treated with HDR brachytherapy and external beam radiotherapy, those who received additional androgen deprivation therapy (ADT) had a significantly reduced risk of biochemical recurrence (BCR), with a hazard ratio of 0.4.

D'Amico high-risk patients showed improved BCR-free survival with the addition of ADT, while no significant benefit was observed for intermediate-risk patients, suggesting that ADT is particularly beneficial for high-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additional androgen deprivation makes the difference: Biochemical recurrence-free survival in prostate cancer patients after HDR brachytherapy and external beam radiotherapy. Schiffmann, J., Lesmana, H., Tennstedt, P., et al.[2018]

In a multicenter phase 2 trial involving 61 intermediate-risk prostate cancer patients, the combination of external beam radiation therapy (EBRT) and transperineal prostate brachytherapy with androgen deprivation therapy (ADT) resulted in a high six-year disease-free survival (DFS) rate of 87.1%.

The treatment was associated with acceptable late toxicity, with only 20% of patients experiencing late grade 2 toxicity and 3% experiencing grade 3 toxicity, indicating a favorable safety profile for this combined therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination external beam radiation and brachytherapy boost with androgen deprivation for treatment of intermediate-risk prostate cancer: long-term results of CALGB 99809. Hurwitz, MD., Halabi, S., Archer, L., et al.[2021]

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 585 high-risk prostate cancer patients treated with high-dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT), a biopsy Gleason score (bGS) of 8 to 10 was identified as the strongest predictor of biochemical relapse-free survival (bRFS), distant metastases-free survival (DMFS), and prostate cancer-specific mortality (PCSM).

The study found that the duration of ADT did not significantly impact patient outcomes, highlighting the importance of tumor characteristics over treatment length in predicting survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. Tendulkar, RD., Reddy, CA., Stephans, KL., et al.[2020]

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]

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 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 173 patients with high-risk localized prostate cancer, long-term androgen deprivation therapy (ADT) for 36 months or more combined with external-beam radiotherapy (EBRT) significantly improved five-year progression-free survival rates (92.8%) compared to short-term ADT (72.9%).

Patients receiving short-term ADT experienced a higher incidence of cardiovascular toxicity (grade II or above) compared to those on long-term ADT, indicating that longer ADT may not only enhance survival but also have a more favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of the duration of hormonal therapy following radiotherapy for localized prostate cancer. Okubo, M., Nakayama, H., Itonaga, T., et al.[2022]

In a study of 46,325 men with high-risk prostate cancer, androgen deprivation therapy (ADT) improved overall survival for those receiving external beam radiation therapy (EBRT) alone, but not for those receiving combined EBRT and brachytherapy.

The findings suggest that while ADT is beneficial with EBRT, it may not enhance survival in patients treated with both EBRT and brachytherapy, highlighting the need for further research to evaluate the risks and benefits of ADT in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of Apparent Survival Benefit With Use of Androgen Deprivation Therapy in Patients With High-risk Prostate Cancer Receiving Combined External Beam Radiation Therapy and Brachytherapy. Yang, DD., Muralidhar, V., Mahal, BA., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10077404/

Outcomes following external beam radiotherapy to the ... 5-year overall survival and prostate cancer-specific survival were 74.4 and 89.1% respectively. 5-year failure-free survival was 55.4%; with 5-year biochemical ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9933910/

Patient-Reported Outcomes after External Beam ... Response rates at 6 months, 1, 3, and 5 years were 95%, 93%, 85%, and 77%, respectively (Supplementary Figure 1). The median follow-up for vital status was 73 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2588931123002845

Prostate Cancer A Systematic Review of the Efficacy and ... We found good evidence that radiotherapy combined with brachytherapy keeps prostate cancer controlled for longer, but it could lead to worse urinary side ...

4. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.33388

Five‐year outcomes from a prospective comparative ... Compared with EBRT alone, EBRT-LDR was associated with clinically meaningful worse urinary irritative and bowel function over 3 years after ...

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

High-dose-rate brachytherapy lowers travel burden for men ... In this study, we compared the travel burdens of patients with prostate cancer choosing HDR-BT monotherapy versus EBRT and SBRT for treatment.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4094624/

Androgen deprivation therapy for prostate cancer: long-term ... ADT can normalize serum prostate specific antigen in over 90% of patients and results in sizable tumor response in 80% to 90%. This treatment can be done either ...

7. ascopubs.org ascopubs.org/doi/10.1200/EDBK_433126

Balancing Hormone Therapy: Mitigating Adverse Effects of ... Treatment advances including ADT have led to improvements in PCa management and survival, with trials reporting median survival of over 6 years ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38164028/

Comparison of Short-Term Outcomes and Safety Profiles ... This study aimed to compare the short-term outcomes and safety profiles of androgen-deprivation therapy (ADT)+abiraterone/prednisone with those of ADT+docetaxel

9. sciencedirect.com sciencedirect.com/science/article/pii/S2588931124000282

A 3-year Interim Analysis of the Observational J-ROCK Study In this study, we compared clinical and safety outcomes with different treatment regimens, using a large series of patients with high-risk metastatic hormone- ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S0302283825004361

Short-term Androgen Deprivation Therapy and High-dose ... Among the 370 patients in the modified intention-to-treat population, 241 (65%) had intermediate-risk and 107 (28%) high-risk prostate cancer.