Prostate SBRT + Triptorelin for Prostate Cancer

(DEFINE Trial)

Overseen By Scott Grimes

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Ottawa Hospital Research Institute

Must be taking: Androgen deprivation

Disqualifiers: Metastases, Other malignancy, Inflammatory bowel, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 week for radiotherapy, 6-24 months for androgen deprivation therapy

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new prostate cancer treatment by combining targeted high-dose radiation therapy (Prostate SBRT with Focal Boost) with hormone therapy (Triptorelin Injection). The goal is to determine if this approach can safely reduce the risk of cancer recurrence without increasing side effects like urinary or bowel problems. Suitable participants have been diagnosed with localized prostate cancer and have already planned hormone therapy. The study targets more challenging cases of prostate cancer, aiming to improve treatment outcomes with fewer side effects. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that participants will be on androgen deprivation therapy with triptorelin, possibly with bicalutamide, so you should discuss your current medications with the trial team to ensure there are no conflicts.

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

Research has shown that using Prostate SBRT, a precise radiation therapy, with a focused boost is generally safe. Studies indicate that patients experience side effects similar to those of traditional treatments. Specifically, adding a focused boost has resulted in side effects remaining within safe limits.

Regarding Triptorelin, used to lower male hormones in androgen deprivation therapy, it has proven effective and safe. In past studies, only a small number of patients experienced serious side effects, while most tolerated the treatment well. The FDA has approved Triptorelin for treating advanced prostate cancer, further assuring its safety.

Overall, both treatments have demonstrated promising safety based on past research and existing approvals. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for prostate cancer?

Researchers are excited about the combination of prostate SBRT with focal boost and Triptorelin for prostate cancer because it offers a targeted and potentially more effective approach than standard treatments. Unlike traditional radiation therapy, which treats the entire prostate uniformly, this approach uses stereotactic body radiotherapy (SBRT) to deliver high doses of radiation specifically to cancerous areas identified by advanced imaging techniques like mpMRI. This precision aims to maximize tumor control while minimizing damage to surrounding healthy tissue. Additionally, combining this with androgen deprivation therapy (ADT) like Triptorelin could enhance treatment efficacy by reducing hormone levels that fuel cancer growth. This approach could provide better outcomes, especially for patients with intermediate to high-risk prostate cancer.

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

Research has shown that prostate stereotactic body radiotherapy (SBRT) with a focal boost, which participants in this trial will receive, has been very successful in treating prostate cancer. Studies have found that this method can precisely target tumors, reducing the chance of cancer recurrence. One study found that SBRT with a focal boost kept the cancer under control for five years with manageable side effects.

In this trial, participants will also receive Triptorelin as part of the androgen deprivation therapy. Triptorelin, used in hormone therapy, effectively treats prostate cancer by significantly reducing testosterone levels, which prostate cancer cells need to grow. Research indicates that over 90% of patients achieve and maintain low testosterone levels with Triptorelin, helping to slow down the cancer. Together, these treatments offer a promising way to manage prostate cancer. ^{1 2 6 7 8}

Who Is on the Research Team?

Scott C. Morgan

Principal Investigator

The Ottawa Hospital Cancer Centre

Are You a Good Fit for This Trial?

Men with a specific type of prostate cancer that's not the mildest but also hasn't spread far (intermediate-risk or high-risk localized). They should have had an MRI within the last year, be able to do most activities without help (ECOG 0-2), and be at least 18 years old. They must agree to hormone therapy with triptorelin, possibly plus another drug.

Inclusion Criteria

My prostate cancer is at an intermediate stage without high-risk features but has certain aggressive traits.

I had a 3 Tesla MRI of the prostate within the last year.

My condition is considered to be at a high risk of getting worse.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Ultra-hypofractionated intensity-modulated, image-guided prostate radiotherapy delivered to 27 Gy in 3 fractions over 5 days, with concurrent/adjuvant androgen deprivation therapy

1 week for radiotherapy, 6-24 months for androgen deprivation therapy

3 visits (in-person) for radiotherapy

Follow-up

Participants are monitored for safety, quality of life, and biochemical control, with primary endpoint being prevalence of grade ≥ 2 genitourinary or gastrointestinal toxicity at 12 months

12 months

Regular follow-up visits

Long-term follow-up

Monitoring for disease-free survival and quality of life up to 2 years

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Prostate SBRT with Focal Boost
• Triptorelin Injection

Trial Overview The trial is testing a new way of giving radiotherapy for prostate cancer. Instead of daily treatments for four weeks, patients get three big doses over one week. The radiation is aimed more precisely using MRI images to target just the tumor areas in hopes of lowering recurrence risk.

How Is the Trial Designed?

Group I: Prostate SBRT with Focal Boost and Androgen Deprivation Therapy Experimental Treatment 2 Interventions

Stereotactic body radiotherapy to 27 Gy in 3 fractions to uninvolved regions of the prostate glad and up to 39 Gy in 3 fractions to mpMRI-defined intraprostatic lesions, with concurrent/adjuvant androgen deprivation therapy (6 months for intermediate risk, 24 months for high risk)

Prostate SBRT with Focal Boost is already approved in European Union, United States for the following indications:

Approved in European Union as Prostate SBRT with Focal Boost for:

• Localized Prostate Cancer
• Intermediate-Risk Prostate Cancer
• High-Risk Prostate Cancer

Approved in United States as Prostate SBRT with Focal Boost for:

• Localized Prostate Cancer
• Intermediate-Risk Prostate Cancer
• High-Risk Prostate Cancer

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Knight Therapeutics (USA) Inc

Industry Sponsor

Trials

6

Recruited

160+

Published Research Related to This Trial

In a phase 1 trial involving 30 patients with intermediate-risk prostate cancer, single-fraction stereotactic body radiation therapy (SBRT) boost was found to be feasible and well tolerated, with a median follow-up of 72 months.

Higher doses of SBRT (up to 15 Gy) resulted in lower prostate-specific antigen (PSA) levels, indicating better treatment efficacy, although there were some cases of significant toxicity, including a grade 4 rectal fistula linked to repeated biopsies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy Boost for Intermediate-Risk Prostate Cancer: A Phase 1 Dose-Escalation Study. Alayed, Y., Loblaw, A., Chu, W., et al.[2021]

In a phase I/II study involving 91 patients with localized prostate cancer, stereotactic body radiation therapy (SBRT) demonstrated a remarkable prostate-specific antigen (PSA) control rate of 99% over a median follow-up of 42 months.

While the maximum-tolerated dose (MTD) was not reached, the study noted a concerning 10.6% incidence of high-grade rectal toxicity at the highest dose level of 50 Gray, prompting the need for dose constraints to reduce this risk in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy for Prostate Cancer: Review of Experience of a Multicenter Phase I/II Dose-Escalation Study. Kim, DW., Straka, C., Cho, LC., et al.[2022]

In a study of 136 patients with low- and intermediate-risk prostate cancer, ultra-hypofractionated stereotactic body radiation therapy (SBRT) doses from 32.5 to 40 Gy were well tolerated, with no severe grade 3 or 4 urinary or rectal toxicities observed.

Higher doses of SBRT were associated with improved tumor clearance, as indicated by a lower incidence of positive posttreatment biopsies and a significant reduction in prostate-specific antigen failure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Outcomes of a Phase 1 Dose-Escalation Study Using Stereotactic Body Radiosurgery for Patients With Low-Risk and Intermediate-Risk Prostate Cancer. Zelefsky, MJ., Kollmeier, M., McBride, S., et al.[2022]

In a phase II trial involving 100 men with intermediate or high-risk prostate cancer, a treatment combining whole gland stereotactic body radiotherapy (SBRT) with a focal boost to visible tumors was found to have acceptable safety, with no severe acute toxicity (grade ≥3) reported.

The treatment resulted in moderate acute toxicity rates, with 34.0% experiencing grade 2 genitourinary issues and 5.0% experiencing grade 2 gastrointestinal issues, indicating that this approach may effectively reduce local recurrence risks while maintaining patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Primary endpoint analysis of the multicentre phase II hypo-FLAME trial for intermediate and high risk prostate cancer. Draulans, C., van der Heide, UA., Haustermans, K., et al.[2021]

Salvage stereotactic body radiation therapy (SBRT) for localized prostate cancer recurrence shows promising efficacy, with 2-year recurrence-free survival rates ranging from 40% to 76% across five studies involving 265 participants.

While genitourinary toxicity was more common than gastrointestinal issues, the rates of severe complications were relatively low, with grade 2 complications ranging from 5% to 22% and no grade 3 gastrointestinal complications reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage stereotactic body radiation therapy for locally recurrent prostate cancer following primary radiation therapy, are benefits worth toxicity risks?: A systematic review. Bray, G., Bahadori, A., Rama, D.[2023]

In a study involving 26 men with early-stage prostate cancer, stereotactic body radiation therapy (SBRT) was successfully delivered, targeting the entire prostate and specific focal lesions, demonstrating feasibility in treatment planning.

Only 7.7% of patients experienced acute urinary symptoms requiring a Foley catheter, well below the 15% threshold for treatment success, indicating that this SBRT approach is associated with low early toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: Acute Toxicity and Dosimetry Results From a Prospective Trial. McDonald, AM., Dobelbower, MC., Yang, ES., et al.[2022]

Stereotactic body radiotherapy (SBRT) is effective for treating localized and metastatic prostate cancer, as prostate cancer shows increased sensitivity to higher radiation doses due to its low α/β ratio.

There is potential for combining SBRT with systemic therapies like androgen deprivation therapy (ADT) and immunotherapy, as SBRT may enhance immune responses, making it a promising area for ongoing research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translating the Immunobiology of SBRT to Novel Therapeutic Combinations for Advanced Prostate Cancer. Adorno Febles, VR., Blacksburg, S., Haas, JA., et al.[2020]

A phase 1 study involving 36 men with intermediate- and high-risk prostate cancer demonstrated that linear accelerator-based stereotactic radiation therapy (SBRT) can safely deliver high doses (up to 30 Gy) while maintaining low toxicity levels, particularly to surrounding organs.

The treatment showed a high rate of freedom from biochemical failure at 3 years (93.3%), with minimal late gastrointestinal toxicity and a manageable rate of genitourinary toxicity (19.3%), indicating its efficacy and safety as a boost therapy for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Results of a Prospective Dose Escalation Study of Linear Accelerator-Based Virtual Brachytherapy (BOOSTER) for Prostate Cancer; Virtual HDR Brachytherapy for Prostate Cancer. Eade, T., Hruby, G., Booth, J., et al.[2022]

In a study of 44 prostate cancer patients treated with a combination of conventional pelvic radiation and an extreme hypofractionation SBRT boost, the five-year progression-free survival rate was an impressive 88.2%, indicating effective long-term control of the disease.

The treatment was associated with low rates of severe toxicity, with only 2.3% experiencing grade III or greater acute genitourinary and gastrointestinal side effects, suggesting that this approach is both effective and safe for patients with advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II Study of Extreme Hypofractionated Stereotactic Body Radiation Therapy Boost to Prostate for Locally Advanced, Node-Positive and Oligometastatic Cancer. Narang, K., Kadian, M., Venkatesan, K., et al.[2021]

Citations

1. redjournal.org redjournal.org/article/S0360-3016(25)06399-0/fulltext

Stereotactic body radiotherapy to the prostate with focal boost SBRT to a dose of 36.25Gy, with a simultaneous integrated boost to the tumour(s) up to 45Gy in 5 fractions, was delivered to 49 men. The primary ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6349624/

Prostate Stereotactic Body Radiation Therapy With a Focal ... This study aimed to report the early toxicity results of a prospective clinical trial of prostate stereotactic body radiation therapy (SBRT) to the entire ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814024035461

Stereotactic body radiotherapy with a focal boost to the ... Prostate SBRT with an integrated focal boost demonstrated excellent 5-year outcomes. ... M.J. Zelefsky et al. Dose escalation for prostate cancer radiotherapy ...

4. thegreenjournal.com thegreenjournal.com/issue/S0167-8140(25)X0003-7?pageStart=26

May 2025 Prostate cancer focal boost versus no boost in 20 fraction external beam radiotherapy: a prospective cohort on dosimetry, toxicity and quality of life

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05705921

NCT05705921 | Standard Moderately Hypofractionated RT ... In the phase II Hypo-FLAME trial, 100 patients with IM or HR PCA were treated with SBRT 35Gy in 5 weekly fractions to the whole prostate with a focal boost up ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0360301624004255

Simultaneous Focal Boost With Stereotactic Radiation ... This study evaluated the toxicity and quality of life (QoL) with CyberKnife-based SBRT and simultaneous integrated boost in localized prostate cancer.

7. thegreenjournal.com thegreenjournal.com/article/S0167-8140(25)00178-1/fulltext

Safety and quality of life of PSMA-PET- and MRI-based ... Safety and quality of life of PSMA-PET- and MRI-based focal dose escalated radiotherapy for intermediate- and high-risk prostate cancer

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301623004467

Toxicity and Patient-Reported Quality-of-Life Outcomes ... Conclusions. SBRT to a dose of 40 Gy to the prostate gland with a simultaneous focal boost up to 45 Gy is well tolerated with similar rates of acute ...