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

Trial Summary

What is the purpose of this trial?

This phase II trial investigates the effect of high dose-rate brachytherapy and stereotactic body radiotherapy in treating patients with prostate adenocarcinoma. Brachytherapy, also known as internal radiation therapy, uses radioactive material placed directly into or near a tumor to kill tumor cells. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method may kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue.

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 data supports the effectiveness of the treatment Combined Radiotherapy for Prostate Cancer?

Research shows that using CyberKnife, a type of precise radiation therapy, can effectively deliver high-dose radiation similar to HDR brachytherapy for prostate cancer. Early clinical observations and comparisons with other treatments suggest it may be a promising option for treating prostate cancer. ^{1 2 3 4 5}

Is combined radiotherapy for prostate cancer safe for humans?

Studies on treatments like CyberKnife and HDR Brachytherapy for prostate cancer show they are generally safe, with some patients experiencing mild to moderate side effects like urinary issues and proctitis (inflammation of the rectum). Most patients remained disease-free and alive at follow-up, indicating a good safety profile. ^{1 5 6 7 8}

How is the combined radiotherapy treatment for prostate cancer different from other treatments?

This treatment combines high-dose-rate brachytherapy (internal radiation) and stereotactic body radiation therapy (CyberKnife), offering precise targeting of prostate cancer with potentially fewer side effects and shorter treatment times compared to traditional methods. It leverages the benefits of both internal and external radiation, making it a unique approach for localized prostate cancer. ^{1 2 5 9 10}

Research Team

Stephanie M Yoon, MD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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]

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]

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]

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]

References

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

Virtual HDR CyberKnife treatment for localized prostatic carcinoma: dosimetry comparison with HDR brachytherapy and preliminary clinical observations. [2022]

2. Ireland 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? [2022]

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

[Robotic radiotherapy for prostate cancer with CyberKnife]. [2022]

4. Australia pubmed.ncbi.nlm.nih.gov

Clinical outcomes of whole pelvis radiotherapy and stereotactic body radiotherapy boost for intermediate- and high-risk prostate cancer. [2018]

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

Stereotactic ablative radiotherapy with CyberKnife in the treatment of locally advanced prostate cancer: preliminary results. [2017]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Cyberknife treatment for low and intermediate risk prostate cancer. [2015]

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

Image-guided stereotactic body radiation therapy for localized prostate cancer. [2022]

9. Australia 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. [2019]

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

High-dose-rate brachytherapy for prostate cancer: Rationale, current applications, and clinical outcome. [2022]