Adaptive SBRT for Prostate Cancer

(ASPIRE Trial)

Overseen By Rachel Glicksman, MD

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: University Health Network, Toronto

Disqualifiers: Elective nodal irradiation, Radiotherapy contraindications, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 2-3 weeks

320 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new type of radiation therapy, called adaptive stereotactic body radiotherapy (SBRT), can manage prostate cancer more effectively than the usual method. Researchers aim to determine if this approach can improve urinary health while maintaining cancer control. The trial seeks participants diagnosed with localized prostate cancer who plan to undergo prostate SBRT, a precise form of radiation treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that patients will be stratified based on the use of androgen deprivation therapy (ADT) and alpha receptor antagonists, which suggests that some medications may be continued.

What prior data suggests that adaptive SBRT is safe for prostate cancer patients?

Research has shown that adaptive stereotactic body radiotherapy (SBRT) is generally easy for patients to handle. Studies indicate that even up to two years after treatment, patients report acceptable side effects. In one study, fewer than 15% of patients experienced serious urinary problems, a common concern with prostate cancer treatments. Another study found that SBRT provides excellent cancer control with manageable side effects for those with localized prostate cancer. These findings suggest that adaptive SBRT is a safe option for treating prostate cancer, with most patients coping well with the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the trial for Adaptive SBRT for prostate cancer because it explores the potential benefits of personalizing radiation therapy. Unlike traditional methods that use a fixed plan, Adaptive SBRT adjusts the radiation dose and delivery based on real-time imaging, which could improve accuracy and minimize damage to surrounding healthy tissues. This technique has the potential to enhance treatment effectiveness while reducing side effects, offering a more tailored approach to prostate cancer care.

What evidence suggests that adaptive SBRT is effective for prostate cancer?

Research has shown that stereotactic body radiotherapy (SBRT) is a promising treatment for prostate cancer that hasn't spread. Studies have found that SBRT can effectively control cancer over the long term, with about 83.6% of patients experiencing no cancer progression for at least five years after treatment. This indicates that most patients remain cancer-free during that period. In this trial, participants will receive either Adaptive SBRT, which adjusts the treatment based on daily changes, or Non-adaptive image-guided SBRT. Researchers believe Adaptive SBRT may improve results, although more data is needed to confirm this. While SBRT generally works well, some patients might experience temporary urinary issues. Overall, SBRT is a strong option for treating localized prostate cancer, and Adaptive SBRT could enhance its effectiveness. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

Men over 18 with localized prostate adenocarcinoma, who are in good physical condition (ECOG performance status of 0-1), and eligible for SBRT treatment can join. Those planning elective nodal irradiation or with contraindications to radiotherapy/MRI cannot participate.

Inclusion Criteria

I am fully active or have some restrictions but can still take care of myself.

I have been diagnosed with prostate cancer.

I am older than 18 years.

Exclusion Criteria

I am scheduled for radiation therapy targeting lymph nodes.

I cannot undergo radiotherapy due to health reasons.

I cannot have an MRI due to certain health reasons.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiotherapy Simulation

Participants undergo radiotherapy simulation with CT and MR simulation (or without MR if contraindication)

1 week

1 visit (in-person)

Treatment

Participants receive either adaptive SBRT or standard image-guided SBRT, with doses of 36.25 Gy in 5 fractions or 42.7 Gy in 7 fractions

2-3 weeks

5-7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including urinary outcomes and acute toxicity

3 months

2 visits (in-person)

Long-term Follow-up

Participants are monitored for late toxicity, biochemical failure, and distant metastases

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Adaptive SBRT

Trial Overview The ASPIRE study is testing if adaptive SBRT provides better urinary outcomes than standard image-guided SBRT in treating localized prostate cancer, while still effectively controlling the disease.

How Is the Trial Designed?

Group I: Non-adaptive image-guided SBRT Experimental Treatment 1 Intervention

Patients will receive prostate SBRT. A dose of either 36.25 Gy in 5 fractions (per PACE-B trial) or 42.7 Gy in 7 fractions (per HYPO-RT-PC trial) will be prescribed as per standard practice at PMH. Patients will receive SBRT every other day, excluding weekends and holidays, as per standard practice. Patients will undergo radiotherapy simulation as per standard practice with CT and MR simulation (or without MR if contraindication).

Group II: Adaptive SBRT Experimental Treatment 1 Intervention

Patients will receive prostate SBRT. A dose of either 36.25 Gy in 5 fractions (per PACE-B trial) or 42.7 Gy in 7 fractions (per HYPO-RT-PC trial) will be prescribed as per standard practice. Patients will receive SBRT every other day, excluding weekends and holidays, as per standard practice. Patients will undergo radiotherapy simulation as per standard practice with CT and MR simulation (or without MR if contraindication).

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Published Research Related to This Trial

In a study involving 31 patients receiving MRI-guided stereotactic body radiotherapy (SBRT) to the prostate bed, significant variations in target volumes and organs-at-risk were observed, with 48.4% of treatment fractions failing at least one dose constraint for critical organs.

Adaptive planning was shown to be highly effective, allowing all treatment fractions to meet target volume criteria and improving compliance with organ-at-risk constraints in 77.4% of cases, suggesting that adaptive planning should be a standard practice in prostate bed SBRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of adaptive planning in margin-reduced, MRI-guided stereotactic body radiotherapy to the prostate bed following radical prostatectomy: Post-hoc analysis of a phase II clinical trial. Nikitas, J., Smith, LM., Gao, Y., et al.[2023]

In a study of 23 patients with high-risk prostate cancer, stereotactic body radiation therapy (SBRT) was found to be feasible and well tolerated, with low rates of severe gastrointestinal (GI) and genitourinary (GU) toxicities.

The treatment resulted in acute grade 1 GI toxicities in only 9.1% of patients and grade 3 GU toxicities in 4.5%, indicating that serious side effects were uncommon, but further long-term follow-up is needed to assess ongoing safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Tolerance Outcomes of Stereotactic Hypofractionated Accelerated Radiation Therapy Concomitant with Pelvic Node Irradiation in High-risk Prostate Cancer. Pinitpatcharalert, A., Happersett, L., Kollmeier, M., et al.[2022]

Online MR-guided adaptive re-planning for prostate cancer SBRT showed a dosimetric benefit in 90% of the ten healthy male volunteers, improving target coverage without increasing radiation exposure to surrounding organs, particularly the rectum.

The benefits of this adaptation were stable for up to 45 minutes, but after 60 minutes, coverage dropped below acceptable levels in 30% of cases, suggesting the need for verification imaging before treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrafractional stability of MR-guided online adaptive SBRT for prostate cancer. Schaule, J., Chamberlain, M., Wilke, L., et al.[2022]

In a study involving 7 patients with localized prostate cancer, the use of AI-augmented online adaptive radiotherapy (ART) significantly improved target coverage (PTV V100) for prostate SBRT, with increases of up to 21.4% for higher dose targets, indicating enhanced treatment efficacy.

The adaptive treatment plans also significantly reduced the dose to the rectum by an average of 38.8 cGy per fraction, improving safety, while still meeting bladder dose constraints, suggesting a favorable therapeutic ratio without increasing the risk of severe side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CT-based online adaptive radiotherapy improves target coverage and organ at risk (OAR) avoidance in stereotactic body radiation therapy (SBRT) for prostate cancer. Waters, M., Price, A., Laugeman, E., et al.[2023]

In a study of 103 patients undergoing stereotactic body radiation therapy (SBRT) for localized prostate cancer, 52% experienced a significant decline in bowel-related quality of life within one week, while 27.5% developed grade 2 or higher rectal toxicity.

Key dosimetric predictors of acute rectal toxicity were identified, specifically rectal D19% and V20Gy, which can help clinicians adjust treatment plans to reduce the risk of these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric predictors of acute bowel toxicity after Stereotactic Body Radiotherapy (SBRT) in the definitive treatment of localized prostate cancer. Repka, MC., Carrasquilla, M., Paydar, I., et al.[2023]

In a study involving 20 prostate cancer patients treated with Adaptive Stereotactic Body Radiotherapy (SBRT), the delivered dose was confirmed to be adequate, ensuring that the target area received at least 95% of the prescribed dose while minimizing exposure to surrounding organs.

The study demonstrated that both the daily re-computed doses and cumulative doses were consistent, indicating that the online MRI guidance effectively maintained treatment accuracy despite potential prostate motion during the longer session times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive SBRT by 1.5 T MR-linac for prostate cancer: On the accuracy of dose delivery in view of the prolonged session time. Ruggieri, R., Rigo, M., Naccarato, S., et al.[2021]

In a study of 254 patients with low-to-intermediate risk prostate cancer undergoing 5-fraction SBRT, significant prostate volume changes were observed, with a mean increase of 6.4% and swelling in 50% of cases.

Despite the prostate volume changes, there was no correlation between these changes and treatment toxicity as measured by patient-reported outcomes, indicating that the adaptive treatment strategy effectively managed volume variations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate volume variation during 1.5T MR-guided adaptive stereotactic body radiotherapy (SBRT) and correlation with treatment toxicity. Nicosia, L., Ravelli, P., Rigo, M., et al.[2023]

In a multicenter trial involving 165 prostate cancer patients, 31% experienced major protocol deviations during stereotactic body radiation therapy (SBRT), with deviations occurring more frequently in the intensity modulated radiation therapy (IMRT) group compared to volumetric modulated arc therapy (VMAT).

VMAT demonstrated superior dosimetric outcomes compared to IMRT, including better dose distribution to the urethra and reduced exposure to the bladder, indicating that VMAT may be a safer and more effective option for delivering SBRT in localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Urethra-Sparing Stereotactic Body Radiation Therapy for Prostate Cancer: Quality Assurance of a Randomized Phase 2 Trial. Jaccard, M., Zilli, T., Dubouloz, A., et al.[2021]

In a study of 14 patients with low-volume metastatic prostate cancer treated with MR-guided adaptive prostate SBRT (SMART), the treatment was well tolerated, with only one patient experiencing mild urinary toxicity and no significant gastrointestinal side effects.

At a median follow-up of 29 months, 11 out of 14 patients maintained local control of their disease, indicating that SMART is an effective and low-risk option for prostate-directed radiotherapy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR-guided prostate SBRT in prostate cancer patients with low-volume metastatic disease. Moningi, S., Choudhury, AD., Martin, NE., et al.[2023]

In a study involving 11 patients and 55 MRI scans, it was found that while the target area (CTV) for radiation therapy remained stable, significant changes occurred in the bladder and rectum volumes, which could affect treatment outcomes.

The use of stereotactic MRI guided adaptive radiotherapy (SMART) was shown to improve dosimetry for 78.2% of treatment fractions, helping to ensure that radiation targets were adequately covered while minimizing exposure to surrounding organs at risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interfractional Geometric Variations and Dosimetric Benefits of Stereotactic MRI Guided Online Adaptive Radiotherapy (SMART) of Prostate Bed after Radical Prostatectomy: Post-Hoc Analysis of a Phase II Trial. Cao, M., Gao, Y., Yoon, SM., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12117833/

Online adaptive stereotactic body radiotherapy for ... The PACE-B RCT demonstrated that SBRT results in excellent oncological outcomes with a 5-year biochemical and biochemical progression-free ...

2. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/prostate-cancer-sbrt-effective-safe

SBRT Proves Effective for Some Prostate Cancers - NCI Trial participants who were randomly assigned to receive SBRT had a higher risk of developing some urinary problems over the first 2 years after ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2452109424001374

Stereotactic Magnetic Resonance–Guided Daily Adaptive ... Over the past decade, clinical trial data have emerged demonstrating SBRT to be a curative option for localized prostate cancer. · SMART has emerged as a ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05628363

Adaptive Stereotactic Body Radiation Therapy to the ... This trial is a prospective clinical trial designed to demonstrate the safety and feasibility of whole-pelvis adaptive prostate stereotactic body radiation ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8557180/

Five-year outcomes of stereotactic body radiation therapy ... Overall, SBRT may offer a higher 5-year bPFS rate of 83.6% and effective symptom relief without severe adverse effects. Additionally, no grade 4 or above ...

6. nature.com nature.com/articles/s41391-025-00947-y

Stereotactic body radiotherapy: a second chance for radio ... The promising long-term clinical outcomes, combined with excellent tolerance, establish SBRT as a valuable salvage treatment option. Further ...