Ablative Radiotherapy for Prostate Cancer

(EARTH Trial)

Overseen By Merrylee McGuffin, MSc

Age: Any Age

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: Sunnybrook Health Sciences Centre

Must not be taking: Androgen deprivation therapy

Disqualifiers: Metastases, Previous radiotherapy, Poor urinary function, 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: 5

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Favorable-risk prostate cancer represent a large proportion of patients diagnosed with prostate cancer and image guided radiation therapy (IGRT) is commonly used to treat these patients using protracted courses of up to 39 treatments over 8 weeks. Stereotactic ablative body radiotherapy (SABR) protocols hold the promise of more convenience, less side effects, less cost and improved system capacity without sacrificing excellent cancer control rates. By the same token, prostate high-dose rate (HDR) brachytherapy boost has been shown to be superior to standard external beam radiation. While two HDR fractions appear to optimize patient convenience and outcomes while minimizing costs, we wanted to determine the tolerability of combining one MR-guided HDR treatment with one SABR treatment to further reduce HDR resource use while maintaining favourable treatment outcomes.

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

The trial does not specify if you need to stop taking your current medications, but it does not allow the use of androgen deprivation therapy. You can continue using 5-alpha-reductase inhibitors.

What data supports the effectiveness of this treatment for prostate cancer?

Research shows that using high-dose-rate (HDR) brachytherapy and stereotactic body radiotherapy (SBRT) can improve outcomes for prostate cancer patients, with studies indicating increased recurrence-free survival and effective dose delivery similar to HDR brachytherapy. ^{1 2 3 4 5}

Is ablative radiotherapy for prostate cancer safe?

Studies show that both high-dose-rate (HDR) brachytherapy and stereotactic body radiotherapy (SBRT) are generally safe for treating prostate cancer, with manageable side effects. Patients may experience some acute (short-term) and late (long-term) side effects, but these treatments are considered effective and safe for prostate cancer. ^{1 5 6 7 8}

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

Ablative radiotherapy for prostate cancer, using high-dose-rate brachytherapy (HDR) and stereotactic body radiation therapy (SBRT), is unique because it delivers high doses of radiation in fewer sessions, which can be more effective and convenient compared to traditional radiation therapy that requires many small doses over several weeks. This approach precisely targets the prostate while sparing surrounding healthy tissues, potentially reducing side effects. ^{1 3 7 9 10}

Research Team

Andrew Loblaw, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

Men with favorable-risk prostate cancer who have not had previous pelvic radiotherapy, hormone therapy for cancer, or certain prostate procedures. They must be able to undergo MRI scans and have a prostate size less than 60 cc without severe urinary symptoms (IPSS ≤15) or other serious health issues.

Inclusion Criteria

My prostate cancer is in the early or favorable intermediate stage.

My prostate cancer diagnosis was confirmed through a tissue examination.

You are able to have a magnetic resonance imaging (MRI) scan.

Exclusion Criteria

My cancer has spread to lymph nodes or other parts of my body.

Poor baseline urinary function defined as International Prostate Symptom Score (IPSS) >15

I have had surgery or HIFU treatment for prostate issues before.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Pre-Treatment

Planning CT and mpMRI imaging for SABR, TRUS with biopsy and insertion of Gold Seed Fiducial Markers, Biobanking of urine, blood and biopsy tissue

2 weeks

1 visit (in-person)

Stereotactic Ablative Body Radiation (SABR)

13.5Gy x 1 to whole prostate + 1cm seminal vesicles, treatment delivered as per standard treatment protocols

1 day

1 visit (in-person)

Inter-treatment

Planning mpMRI and TRUS imaging for HDR, Biobanking of urine and blood

1 week

1 visit (in-person)

HDR Brachytherapy

13.5 Gy x 1 to the prostate, <20 Gy to DIL, HDR dose prescription delivered in one fraction

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of acute and late toxicities, bloodwork, and quality of life evaluations

5 years

Multiple visits (in-person and virtual) at specified intervals

Treatment Details

Interventions

• HDR
• Stereotactic Ablative Body Radiotherapy

Trial Overview The trial is testing a combination of two advanced radiation treatments: one high-dose rate (HDR) brachytherapy session and one stereotactic ablative body radiotherapy (SABR) session. The goal is to see if this duo can treat prostate cancer effectively with fewer sessions and side effects.

Participant Groups

Group I: Intervention Arm Experimental Treatment 1 Intervention

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

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

• Prostate cancer

Approved in European Union as HDR Brachytherapy for:

• Prostate cancer
• Cervical cancer
• Breast cancer

Approved in Canada as High-Dose Rate Brachytherapy for:

• Prostate cancer
• Gynecological cancers

Who Is Running the Clinical Trial?

Sunnybrook Health Sciences Centre

Lead Sponsor

Trials

693

Recruited

1,569,000+

Findings from Research

In a study of 38 prostate cancer patients treated with stereotactic body radiotherapy (SBRT), the treatment was well tolerated, with only 42% experiencing mild acute gastrourinary toxicity and no severe acute side effects reported.

The median PSA nadir for patients receiving SBRT boost was 0.10 ng/mL, indicating effective treatment outcomes comparable to those achieved with HDR brachytherapy, suggesting SBRT could be a viable alternative for prostate cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy as monotherapy or post-external beam radiotherapy boost for prostate cancer: technique, early toxicity, and PSA response. Jabbari, S., Weinberg, VK., Kaprealian, T., et al.[2018]

Stereotactic body radiotherapy (SBRT) as a boost after external-beam radiotherapy shows promising biochemical control rates for intermediate and high-risk prostate cancer, with 5-year rates of 90% for biochemical control and 83% for recurrence-free survival.

The treatment was well-tolerated, with no severe acute gastrointestinal or genitourinary toxicities reported, indicating that SBRT could be a safe alternative for patients who are not candidates for high dose rate brachytherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of hypofractionated stereotactic body radiotherapy boost for intermediate and high-risk prostate cancer. Anwar, M., Weinberg, V., Seymour, Z., et al.[2022]

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]

In a study of 101 patients with higher-risk localized prostate cancer, combining high-dose-rate (HDR) brachytherapy with stereotactic body radiation therapy (SBRT) resulted in a very low incidence of severe toxicities, with no grade ≥3 toxicities observed and only 0.99% experiencing grade 2 gastrointestinal issues.

The treatment showed promising efficacy, with a 2-year biochemical relapse-free survival rate of 97%, indicating strong cancer control outcomes alongside a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early outcomes of high-dose-rate brachytherapy combined with ultra-hypofractionated radiation in higher-risk prostate cancer. Gorovets, D., Hopkins, M., Kollmeier, M., et al.[2021]

In a study of 79 prostate cancer patients treated with virtual HDR SBRT, the median PSA level dropped significantly from 5.6 ng/mL to 0.05 ng/mL after 5 years, indicating effective cancer control.

The treatment resulted in a high 5-year biochemical-relapse-free survival rate of 100% for low-risk and 92% for intermediate-risk patients, with manageable toxicity levels, including only 6% experiencing late grade 3 GU toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations. Fuller, DB., Naitoh, J., Mardirossian, G.[2023]

In a study of 185 patients with low- and intermediate risk prostate cancer, the 26 Gy/2 fractions high-dose-rate brachytherapy (HDR BT) showed equivalent biochemical control rates (BCRs) to the 36.25 Gy/5 fractions stereotactic ablative radiotherapy (SABR) while having lower rates of gastrointestinal and genitourinary toxicities.

The 5-year BCRs were significantly better for the 26 Gy/2 fractions HDR BT and 36.25 Gy/5 fractions SABR compared to the single dose 19 Gy HDR BT, suggesting that the two-fraction HDR BT regimen is a promising treatment option that warrants further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated radiotherapy for low- and intermediate risk prostate cancer: High-dose-rate brachytherapy vs stereotactic ablative radiotherapy. Tsang, YM., Tharmalingam, H., Belessiotis-Richards, K., 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 34 high-risk prostate cancer patients, stereotactic body radiotherapy (SBRT) as a boost after pelvic radiotherapy showed excellent biochemical control, with none of the patients experiencing a relapse over an average follow-up of 41.2 months.

The treatment was associated with manageable side effects, with 14% experiencing grade 2 or higher gastrointestinal toxicity and 29% experiencing genitourinary toxicity, but no severe late toxicities were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy as a boost after external beam radiotherapy for high-risk prostate cancer patients. Turna, M., Akboru, H., Ermis, E., 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]

Stereotactic body radiation therapy (SBRT) and high-dose-rate brachytherapy (HDRBT) are effective modern treatments for prostate cancer, allowing for higher doses of radiation to be delivered precisely to the tumor while protecting surrounding healthy tissue.

These treatments are particularly beneficial for men with low- and intermediate-risk prostate cancer, as they can potentially shorten treatment duration while maintaining effective oncological outcomes and minimizing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ablative Radiotherapy in Prostate Cancer: Stereotactic Body Radiotherapy and High Dose Rate Brachytherapy. Ma, TM., Lilleby, O., Lilleby, WA., et al.[2023]

References

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

Stereotactic body radiotherapy as monotherapy or post-external beam radiotherapy boost for prostate cancer: technique, early toxicity, and PSA response. [2018]

2. England pubmed.ncbi.nlm.nih.gov

Outcomes of hypofractionated stereotactic body radiotherapy boost for intermediate and high-risk prostate cancer. [2022]

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

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

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

Early outcomes of high-dose-rate brachytherapy combined with ultra-hypofractionated radiation in higher-risk prostate cancer. [2021]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated radiotherapy for low- and intermediate risk prostate cancer: High-dose-rate brachytherapy vs stereotactic ablative radiotherapy. [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. India pubmed.ncbi.nlm.nih.gov

Stereotactic body radiotherapy as a boost after external beam radiotherapy for high-risk prostate cancer patients. [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. Switzerland pubmed.ncbi.nlm.nih.gov

Ablative Radiotherapy in Prostate Cancer: Stereotactic Body Radiotherapy and High Dose Rate Brachytherapy. [2023]