Combined Radiotherapy for Prostate Cancer

(HYDRA Trial)

Overseen By Maria Casado

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Jonsson Comprehensive Cancer Center

Disqualifiers: Neuroendocrine carcinoma, Invasive malignancy, Metastases, Inflammatory bowel disease, others

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

Compensation: Varies

Number of Visits: 90

Duration: 2 weeks

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat prostate cancer using two types of radiation therapy. The first, high dose-rate brachytherapy (internal radiation therapy), places radiation directly inside or near the tumor. The second, stereotactic body radiation therapy (stereotactic ablative radiotherapy or CyberKnife), uses precise targeting to deliver fewer, more effective doses. The goal is to kill cancer cells while minimizing damage to surrounding healthy tissue. Men with confirmed intermediate- to high-risk prostate cancer that hasn't spread beyond the prostate might be suitable candidates for this trial. As an unphased trial, this study provides a unique opportunity to explore innovative treatments that could potentially improve outcomes for prostate cancer patients.

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 trial coordinators or your doctor.

What prior data suggests that this combined radiotherapy method is safe for treating prostate cancer?

Previous studies have shown that high-dose rate brachytherapy is well-tolerated by prostate cancer patients. Research indicates it is generally safe, with patients experiencing good cancer control rates. Importantly, the treatment can be used alone or with other radiation types and is effective without causing major side effects for many patients.

Similarly, studies on stereotactic body radiation therapy (SBRT) show it is also safe and well-tolerated. This therapy delivers precise radiation doses to tumors while minimizing impact on nearby healthy tissues. Patients have reported only minor side effects, and it has proven effective for those with low to intermediate risk prostate cancer.

Both treatments under study are generally considered safe options for treating prostate cancer, based on prior research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using High-Dose Rate Brachytherapy (HDR-BT) combined with Stereotactic Body Radiation Therapy (SBRT) for prostate cancer because this approach allows for highly precise targeting of the tumor. Unlike traditional external beam radiation therapy, which typically requires several weeks of treatment, HDR-BT and SBRT can deliver higher doses of radiation over a shorter period, potentially reducing treatment time to just a couple of weeks. This combination not only aims to minimize damage to surrounding healthy tissue but also offers the potential for fewer side effects and a quicker recovery, making it a promising alternative to existing treatments for prostate cancer.

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

Research has shown that high-dose rate brachytherapy (HDR) effectively controls prostate cancer. Studies have found strong disease control when HDR is used alone or with external radiation, with patients experiencing long-term cancer control for up to eight years. In this trial, participants will receive a combination of HDR and stereotactic body radiation therapy (SBRT).

For stereotactic body radiation therapy (SBRT), studies indicate it provides excellent long-term disease control. SBRT has proven to be as effective as standard radiation therapy in managing prostate cancer. It also offers the advantage of fewer treatment sessions, which can be more convenient for patients. ^{1 3 4 6 7}

Who Is on the Research Team?

Stephanie M Yoon, MD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

Men aged 18+ with intermediate to high-risk prostate adenocarcinoma (T1c-T3b, PSA > 10, Gleason score >=7) without metastases or prior major treatments for prostate cancer. They must be able to undergo sedation or anesthesia, have a prostate size <=60cc, and an ECOG performance status of 0-2.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

I can safely undergo procedures with sedation or general anesthesia.

International Prognostic Scoring System (IPSS) score =< 15

Exclusion Criteria

I have had surgery or specific treatments for prostate cancer.

I have a history of inflammatory bowel disease or a high risk for radiation side effects.

I have had radiation treatment to my pelvis or seed implant therapy in my prostate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo HDR-BT for up to 24 hours and SBRT every other day or consecutive days for up to 14 consecutive days

2 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Within 90 days, every 3 months for 24 months, then every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• High-Dose Rate Brachytherapy
• Stereotactic Body Radiation Therapy

Trial Overview The trial is testing the combination of high dose-rate brachytherapy (internal radiation) and stereotactic body radiotherapy (precise external radiation). It aims to see if this approach effectively treats prostate adenocarcinoma with fewer doses and less damage to healthy tissue.

How Is the Trial Designed?

Group I: Treatment (HDR-BT, SBRT) Experimental Treatment 2 Interventions

Patients undergo HDR-BT for up to 24 hours and undergo SBRT every other day or consecutive days for up to 14 consecutive chronologic days in the absence of disease progression or unacceptable toxicity.

High-Dose Rate Brachytherapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as High-Dose Rate Brachytherapy for:

• Prostate adenocarcinoma
• Cervical cancer
• Breast cancer
• Skin cancer

Approved in European Union as High-Dose Rate Brachytherapy for:

• Prostate adenocarcinoma
• Cervical cancer
• Breast cancer
• Skin cancer
• Esophageal cancer

Approved in Canada as High-Dose Rate Brachytherapy for:

• Prostate adenocarcinoma
• Cervical cancer
• Breast cancer

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Published Research Related to This Trial

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]

In a study of 39 patients with intermediate- to high-risk prostate cancer, the combination of whole pelvis radiotherapy (WPRT) and a Cyberknife SBRT boost resulted in a high 5-year biochemical failure-free survival rate of 94.7%.

The treatment was associated with minimal toxicity, with no grade 3 acute side effects reported, although 23% experienced grade 2 acute genitourinary and 21% had grade 2 acute gastrointestinal toxicities, which mostly resolved within 2 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes of whole pelvis radiotherapy and stereotactic body radiotherapy boost for intermediate- and high-risk prostate cancer. Kim, HJ., Phak, JH., Kim, WC.[2018]

Stereotactic body radiation therapy (SBRT) using CyberKnife for localized prostate cancer was found to be safe, with no severe treatment-related toxicities (grade 3 or higher) reported among 44 patients over a median follow-up of 40 months.

The treatment showed excellent efficacy, with a 100% cause-specific survival rate and progression-free survival rate, and a high biochemical failure-free rate of 90.8% for high-risk patients, particularly with the 34 Gy in 4 fractions regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided stereotactic body radiation therapy for localized prostate cancer. Kang, JK., Cho, CK., Choi, CW., et al.[2022]

The CyberKnife robotic system for prostate cancer treatment shows promise as a comparable option to high dose rate brachytherapy, suggesting it could be a viable alternative in radiation therapy.

While the CyberKnife may be seen as a technical improvement over existing treatments, further clinical and economic evaluations are necessary to fully understand its effectiveness and potential benefits in prostate cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Robotic radiotherapy for prostate cancer with CyberKnife]. Hannoun-Levi, JM., Benezery, K., Bondiau, PY., et al.[2022]

In a study involving 32 patients with early-stage prostate cancer treated with Cyberknife, 29 patients remained free of disease at the last follow-up, indicating strong efficacy of this treatment.

While some patients experienced mild to moderate side effects, including acute genitourinary toxicity and proctitis, all patients were alive at the last follow-up, suggesting that Cyberknife is a safe option for localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cyberknife treatment for low and intermediate risk prostate cancer. Detti, B., Bonomo, P., Masi, L., et al.[2015]

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]

CyberKnife (CK) stereotactic body radiotherapy (SBRT) can effectively replicate the dose and distribution of high-dose-rate (HDR) brachytherapy for prostate cancer, with similar planning target volume coverage and improved urethra dose sparing in 9 out of 10 patients.

Early clinical results show a significant reduction in prostate-specific antigen levels (86% decrease from baseline) after CK SBRT, with minimal and transient acute toxicity, primarily urologic, indicating a promising safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virtual HDR CyberKnife treatment for localized prostatic carcinoma: dosimetry comparison with HDR brachytherapy and preliminary clinical observations. Fuller, DB., Naitoh, J., Lee, C., et al.[2022]

CyberKnife stereotactic ablative radiotherapy (SABR) for treating intermediate- to very-high-risk prostate cancer showed a high 3-year biochemical relapse-free survival rate of 90.2%, indicating its efficacy in managing this condition.

The treatment was well-tolerated, with no patients experiencing severe toxicity (≥ grade 3), and only mild genitourinary and gastrointestinal side effects were reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. Fan, CY., Chao, HL., Huang, WY., et al.[2017]

Stereotactic ablative radiation (SAbR) at a dose of 45 Gy in 5 fractions shows a promising safety profile for treating localized prostate cancer, with acute urinary and gastrointestinal toxicity rates of 20.4% and 7.3%, respectively, and low rates of late toxicity after 2 years.

The treatment demonstrated excellent efficacy, with a biochemical failure-free survival rate of 100% at 1 year and 98.7% at 2 years, indicating strong disease control outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer. Chen, L., Gannavarapu, BS., Desai, NB., et al.[2022]

In a study comparing two-fraction stereotactic ablative radiotherapy (SABR) and two-fraction high dose rate (HDR) brachytherapy for localized prostate cancer, both treatments showed similar rates of biochemical failure after 72 months, with SABR having a slightly lower failure rate of 3.5% compared to 12.8% for HDR.

Both SABR and HDR treatments exhibited low rates of significant toxicity and maintained comparable quality of life scores, suggesting that SABR is a safe and effective alternative to HDR brachytherapy for prostate cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-fraction stereotactic ablative radiotherapy (SABR) versus two-fraction high dose rate (HDR) brachytherapy for localized prostate cancer: Does dose heterogeneity matter? Correa, RJM., Morton, G., Chung, HT., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6043748/

High dose-rate brachytherapy in the treatment of prostate cancer In summary, HDR brachytherapy boost results in a high disease control rates for men with localized prostate cancer, with strong evidence that it provides ...

2. advancesradonc.org advancesradonc.org/article/S2452-1094(25)00148-4/fulltext

High-Dose-Rate Brachytherapy Boost for Prostate Cancer However, studies have shown that combining brachytherapy with EBRT results in a higher rate of cancer control than EBRT alone. Nevertheless, the ...

3. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00651-0/fulltext

Prostate high dose-rate brachytherapy as monotherapy for ... HDR monotherapy delivered in two fractions of 13.5 Gy demonstrated a persistent cancer control rate at 8 years and was well-tolerated. Single- ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425001484

High-dose-rate brachytherapy boost for prostate cancer: A ... Overall, this study demonstrated the efficacy of EBRT-boosted brachytherapy in the treatment of intermediate- and high-risk prostate cancer, ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12190164/

Long-Term Outcomes After High-Dose-Rate Brachytherapy ... These outcomes included lower biochemical recurrence-free survival at 5 and 8 years, lower OS, and lower prostate CSS compared to patients with ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38160102/

Safety of high-dose rate (HDR) brachytherapy for patients ... Conclusions: HDR-BT is a safe treatment for patients with prostate cancer who previously received RT for rectal cancer. Further studies are ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405630825000138

Effectiveness, toxicity and impact on quality of life of high ... High-dose-rate brachytherapy is an option for prostate cancer patients. •. Two fractions of high-dose-rate brachytherapy as monotherpy appear to be safe. •.