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?

The ASPIRE study is a Phase III randomized, single-center study designed to evaluate whether adaptive stereotactic body radiotherapy (SBRT) offers superior clinical benefits compared to standard image-guided SBRT for patients with localized prostate cancer. It aims to explore whether adaptive SBRT can improve urinary outcomes while maintaining effective cancer control. This interventional study is randomized, single-institution, and includes 320 participants with localized prostate cancer. Patients will be stratified based on fractionation schedules (5 vs. 7 fractions), use of rectal spacers, androgen deprivation therapy (ADT), and baseline alpha receptor antagonist use. Participants will be randomized to receive either adaptive SBRT or standard image-guided SBRT, with both arms adhering to established dosing protocols. Inclusion criteria includes an age greater than 18 years, diagnosed with localized prostate adenocarcinoma, and an ECOG performance status of 0-1, Eligible for prostate SBRT. The exclusion criteria includes patients who plan for elective nodal irradiation and contraindications to radiotherapy or MRI (for MR-Linac patients).

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.

Is Adaptive SBRT safe for humans?

Research on SBRT for prostate cancer shows it is generally safe, but some studies have noted potential side effects like bowel and rectal toxicity (irritation or damage to the bowel and rectum). Adaptive SBRT aims to improve safety by adjusting treatment to better protect healthy tissues. ^{1 2 3 4 5}

How is Adaptive SBRT different from other treatments for prostate cancer?

Adaptive SBRT for prostate cancer is unique because it uses advanced imaging techniques like MRI or CT to adjust the radiation plan daily, improving accuracy and reducing damage to surrounding healthy tissues. This approach allows for better targeting of the cancer while minimizing side effects, which is not typically possible with standard radiation treatments. ^{4 6 7 8 9}

What data supports the effectiveness of the treatment Adaptive SBRT for prostate cancer?

Research shows that Adaptive SBRT for prostate cancer can improve the accuracy of targeting the cancer while reducing exposure to nearby healthy organs. This is achieved by adjusting the treatment plan daily based on changes in the patient's anatomy, potentially leading to better outcomes and fewer side effects. ^{4 6 7 9 10}

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]

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 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]

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]

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 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 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]

Citations

1. Ireland 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. [2023]

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

Intrafractional stability of MR-guided online adaptive SBRT for prostate cancer. [2022]

3. Ireland 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. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

MR-guided prostate SBRT in prostate cancer patients with low-volume metastatic disease. [2023]

5. Switzerland 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. [2021]

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

Early Tolerance Outcomes of Stereotactic Hypofractionated Accelerated Radiation Therapy Concomitant with Pelvic Node Irradiation in High-risk Prostate Cancer. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Dosimetric predictors of acute bowel toxicity after Stereotactic Body Radiotherapy (SBRT) in the definitive treatment of localized prostate cancer. [2023]

8. Ireland pubmed.ncbi.nlm.nih.gov

Prostate volume variation during 1.5T MR-guided adaptive stereotactic body radiotherapy (SBRT) and correlation with treatment toxicity. [2023]

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

Urethra-Sparing Stereotactic Body Radiation Therapy for Prostate Cancer: Quality Assurance of a Randomized Phase 2 Trial. [2021]

10. Italy 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. [2021]