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

Trial Summary

What is the purpose of this trial?

External beam radiotherapy combined with androgen deprivation therapy is a standard treatment option for localized prostate cancer. The current standard involves delivering radiotherapy uniformly throughout the prostate gland in daily fractions, five days per week, for approximately four weeks. In this study, radiotherapy will be delivered using an ultra-hypofractionated approach in three larger fractions on alternating days over one week Multiparametric magnetic resonance imaging will be used to guide focal dose escalation to parts of the gland harboring tumor, which could potentially reduce the risk of cancer recurrence compared to standard dose of radiotherapy. The aim of this study is to confirm that this approach can be delivered safely, that is, with rates of urinary and bowel side effects at 1 year of follow-up that are not significantly greater than the current standard.

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.

What data supports the effectiveness of the treatment Prostate SBRT + Triptorelin for Prostate Cancer?

Research shows that stereotactic body radiation therapy (SBRT) is effective in treating prostate cancer by delivering high doses of radiation to the tumor, which can reduce the risk of cancer returning. Studies have also shown that SBRT with a boost (extra dose) to the tumor can be a promising approach for intermediate and high-risk prostate cancer, potentially mimicking the effects of other high-dose treatments. ^{1 2 3 4 5}

Is Prostate SBRT with Triptorelin safe for humans?

Research on prostate stereotactic body radiation therapy (SBRT) with a focal boost shows that it has been studied for safety, with early results indicating manageable side effects. Studies on SBRT for prostate cancer have reported on toxicity outcomes, suggesting it is generally safe, though specific side effects can vary. Triptorelin, also known as Decapeptyl or Trelstar, is a medication used in hormone therapy and is generally considered safe, but it can have side effects like hot flashes and fatigue. ^{2 3 6 7 8}

How is the treatment Prostate SBRT with Focal Boost different from other prostate cancer treatments?

Prostate SBRT with Focal Boost is unique because it uses high-dose radiation in fewer sessions (ultra-hypofractionated) and targets the main tumor more intensely (focal boost), potentially reducing the risk of cancer returning while minimizing damage to surrounding healthy tissue. ^{1 2 3 4 9}

Research Team

Scott C. Morgan

Principal Investigator

The Ottawa Hospital Cancer Centre

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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 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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Primary endpoint analysis of the multicentre phase II hypo-FLAME trial for intermediate and high risk prostate cancer. [2021]

2. United States 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. [2022]

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

Stereotactic Body Radiation Therapy Boost for Intermediate-Risk Prostate Cancer: A Phase 1 Dose-Escalation Study. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Stereotactic Body Radiation Therapy for Prostate Cancer: Review of Experience of a Multicenter Phase I/II Dose-Escalation Study. [2022]

5. United States 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. [2021]

6. United States 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. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Translating the Immunobiology of SBRT to Novel Therapeutic Combinations for Advanced Prostate Cancer. [2020]

8. United States 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. [2022]

9. United States 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. [2023]