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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating prostate cancer by combining two types of radiation therapy. The researchers aim to determine if one dose of MR-guided high-dose rate (HDR) brachytherapy, alongside one session of stereotactic ablative body radiotherapy (SABR), can maintain effective cancer control with fewer side effects and lower costs. The trial seeks men with low or favorable-risk prostate cancer who have not undergone previous pelvic radiation or surgery and can undergo MRI scans. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in prostate cancer care.

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.

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

Research shows that high-dose rate (HDR) brachytherapy is safe for prostate cancer patients. Studies indicate that two doses are generally well-tolerated, with patients rarely experiencing severe side effects.

Similarly, research on stereotactic ablative body radiotherapy (SABR) demonstrates its safety for treating prostate cancer. SABR, administered in multiple doses, has shown promising safety results.

Various studies have tested both treatments, confirming their manageability for patients. These findings suggest that the treatments in the trial are generally well-tolerated and have a strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the ablative radiotherapy treatments for prostate cancer because they offer a more precise and potentially less invasive option compared to traditional therapies like surgery or conventional radiation therapy. High-dose-rate (HDR) brachytherapy delivers targeted radiation directly to the tumor, minimizing damage to surrounding healthy tissue. Meanwhile, Stereotactic Ablative Body Radiotherapy (SABR) uses advanced imaging to focus high doses of radiation with pinpoint accuracy, reducing treatment times significantly. These innovations could lead to fewer side effects and quicker recovery for patients, making them promising alternatives to the standard of care.

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

Research shows that both high-dose rate (HDR) brachytherapy and Stereotactic Ablative Body Radiotherapy (SABR) effectively treat prostate cancer. In this trial, participants will receive one of these treatments. Studies on HDR brachytherapy highlight its success, especially when combined with external beam radiation, in controlling prostate cancer, with cure rates around 85% for more challenging cases. SABR has also demonstrated promising results, with a 96% success rate in controlling prostate cancer three years after treatment. It is known for having few side effects and being well-tolerated by patients. Both treatments offer strong long-term control of the disease for low- and intermediate-risk prostate cancer. These therapies could provide effective and convenient options for managing prostate cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Andrew Loblaw, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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]

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]

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]

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 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 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]

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]

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 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]

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]

Citations

1. 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 ...

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

Prostate high dose-rate brachytherapy as monotherapy for ... We report on the efficacy of a randomized Phase II trial comparing HDR monotherapy delivered as 27 Gy in 2 fractions vs. 19 Gy in 1 fraction with a median ...

3. 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, ...

4. urotoday.com urotoday.com/conference-highlights/astro-2024/astro-2024-prostate-cancer/155302-astro-2024-a-randomized-comparison-of-low-dose-rate-or-high-dose-rate-brachytherapy-combined-with-external-beam-radiation-for-unfavorable-intermediate-or-high-risk-prostate-cancer-efficacy-results-at-median-6-years.html

ASTRO 2024: A Randomized Comparison of Low Dose ... HDR and LDR boost both appear to be highly effective for the treatment of unfavorable risk prostate cancer, with 85% biochemical cure (i.e., PSA ...

5. link.springer.com link.springer.com/article/10.1007/s11604-024-01621-4

Long-term outcomes of high-dose-rate brachytherapy and ... Our study demonstrated that HDR-BT in combination with EBRT without additional HT resulted in 7-year bFFF, CSS, and OS rates of 74.2, 100, and ...

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 ... We found that two-fraction HDR-BT as monotherapy among patients with mainly low- and intermediate-risk prostate cancer appears to be safe in terms of ...

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

High-Dose-Rate Brachytherapy Boost for Prostate Cancer a single high-dose-rate (HDR) of 15 Gy combined with external radiation therapy of 40 to 50 Gy results in disease-free survival of over 90% for intermediate- ...