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

Trial Summary

What is the purpose of this trial?

This study is trying to find out if the combination of Androgen deprivation therapy (ADT), MRI guided high dose radiation (HDR) brachytherapy treatment (internal radiation implant procedure) and external beam radiation therapy (EBRT) treatments lead to less side effects. This study is also looking at patient outcomes, quality of life, and overall survival for patients receiving this treatment.

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.

What data supports the effectiveness of the treatment EBRT + ADT + HDR Brachytherapy for Prostate Cancer?

There is evidence that combining external beam radiotherapy (EBRT) with high dose rate brachytherapy (HDR) is effective for treating intermediate and high-risk prostate cancer. However, the benefits of adding androgen deprivation therapy (ADT) to this combination are unclear, as some studies suggest less benefit from ADT when used with dose-escalated radiation treatments. ^{1 2 3 4 5}

Is the combination of EBRT, ADT, and HDR Brachytherapy safe for prostate cancer treatment?

Numerous studies have reported that HDR brachytherapy is safe and effective, and it has been used with EBRT to increase the dose to the prostate without injuring the bladder or rectum. However, the use of ADT (hormone therapy) has been associated with some adverse events. ^{1 4 6 7 8}

How is the treatment of EBRT + ADT + HDR Brachytherapy for prostate cancer different from other treatments?

This treatment combines three approaches: hormone therapy (ADT) to reduce male hormones that fuel cancer growth, external beam radiation (EBRT) to target cancer from outside the body, and high-dose rate brachytherapy (HDR) which delivers radiation directly inside the prostate. This combination aims to enhance effectiveness by attacking the cancer in multiple ways, which may be more beneficial for certain risk groups compared to using these treatments individually. ^{3 4 5 9 10}

Research Team

Chris Luminais, MD

Principal Investigator

University of Virginia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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 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]

References

1. United States 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. [2018]

2. United States 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. [2019]

3. Germany 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. [2018]

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

Redefining high-risk prostate cancer based on distant metastases and mortality after high-dose radiotherapy with androgen deprivation therapy. [2020]

5. 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]

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

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

7. 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]

8. Greece pubmed.ncbi.nlm.nih.gov

Impact of the duration of hormonal therapy following radiotherapy for localized prostate cancer. [2022]

9. 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]

10. United States 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. [2021]