Adaptive Radiation Therapy for Prostate Cancer

(ARTIA-Prostate Trial)

Recruiting at 6 trial locations

Overseen By Claire McCann, PhD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Varian, a Siemens Healthineers Company

Must not be taking: Cytotoxic chemotherapy

Disqualifiers: Node positive cancer, Inflammatory bowel, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: 2 weeks

132 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of delivering radiation therapy for prostate cancer to determine if it reduces urinary side effects. The focus is on adaptive radiation therapy, which adjusts treatment as needed while sparing the urethra. This includes Stereotactic Body Radiation Therapy (SBRT), a precise form of radiation therapy. The trial targets men with low to intermediate risk prostate cancer, confirmed by biopsy, and no significant lesions near the urethra. Participants should have a prostate size of 80cc or less and be able to complete symptom questionnaires. The trial aims to improve comfort and reduce side effects during prostate cancer treatment. As an unphased trial, it offers an opportunity to contribute to innovative research that could enhance future prostate cancer treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow for androgen deprivation therapy. If you are on cytotoxic chemotherapy, you cannot participate in the trial.

What prior data suggests that this adaptive radiotherapy technique is safe for prostate cancer patients?

Studies have shown that stereotactic body radiation therapy (SBRT) for prostate cancer is generally safe, with low rates of side effects. In one study, researchers found that SBRT had side effects similar to regular radiation therapy. Specifically, about 27% of men receiving SBRT reported urinary problems over five years, compared to 18% in the standard radiation group.

Another study examined a version of SBRT that aims to protect the urethra by targeting the prostate more precisely. This approach, called adaptive SBRT with urethral sparing, might reduce the risk of urinary side effects. While researchers are still collecting data, early results suggest this method could have fewer impacts on quality of life than traditional methods.

Overall, while some patients experience side effects like urinary issues, SBRT, especially with these new techniques, is considered well-tolerated for treating prostate cancer. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Adaptive SBRT with Urethral Sparing is unique because it customizes radiation therapy daily to target prostate cancer more precisely while sparing the urethra. Traditional radiation treatments often expose healthy tissues to radiation, but this method delivers a high dose of 40 Gy specifically to the prostate and significantly less to the urethra, reducing potential side effects. Researchers are excited because this approach could enhance the effectiveness of treatment while minimizing harm to nearby healthy tissues, potentially improving patients' quality of life.

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

Research shows that stereotactic body radiation therapy (SBRT) effectively treats prostate cancer. Studies have found that patients receiving SBRT often experience high rates of cancer remission, as confirmed by lab tests. SBRT also helps control the disease long-term in men with low- and intermediate-risk prostate cancer, which this trial focuses on. However, some patients might experience urinary issues in the first two years after treatment. This trial tests an adaptive SBRT approach with urethral sparing, which may reduce these side effects while maintaining effectiveness. ^{4 5 6 7 8}

Who Is on the Research Team?

Jonathan Leeman, MD

Principal Investigator

Brigham and Women's Hospital

Jeremy Bredfeldt, PhD

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

This trial is for men at least 18 years old with low or intermediate risk prostate cancer confirmed by biopsy. Their prostate must be relatively small (≤80cc), they should have mild to moderate urinary symptoms (AUA/IPSS score ≤ 15), and be in fair health (ECOG ≤2 or Karnofsky ≥60%). They must not have aggressive cancer lesions touching the urethra, can fill out questionnaires, and agree to sign consent.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

AUA/IPSS score is ≤ 15

Patient has the ability to complete required patient questionnaires

Exclusion Criteria

I am currently not on cytotoxic chemotherapy, but I may be on hormone therapy.

Patient cannot undergo prostate MRI

My prostate cancer has spread to my lymph nodes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Daily adaptive stereotactic body radiation therapy delivering 40 Gy in 5 fractions to the prostate while delivering 35-36 Gy in 5 fractions to the urethra

2 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including patient-reported outcomes and physician-reported toxicities

5 years

Regular visits at 6 weeks, 3 months, 6 months, 12 months, 18 months, 2 years, 3 years, 4 years, and 5 years

What Are the Treatments Tested in This Trial?

Interventions

• SBRT

Trial Overview The study tests a new way of giving radiation therapy called daily adaptive SBRT that tries to protect the urethra from damage. It's hoped this method will reduce immediate urinary side effects compared to traditional methods. Patients' experiences are tracked using a specific questionnaire.

How Is the Trial Designed?

Group I: Adaptive SBRT with Urethral Sparing Experimental Treatment 1 Intervention

Daily adaptive stereotactic body radiation therapy delivering 40 Gy in 5 fractions to the prostate while delivery 35-36 Gy in 5 fractions to the urethra.

SBRT is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Approved in European Union as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors
• Bone metastases

Approved in Canada as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer
• Spinal tumors

Approved in Japan as SBRT for:

• Prostate cancer
• Lung cancer
• Liver cancer
• Pancreatic cancer

Who Is Running the Clinical Trial?

Varian, a Siemens Healthineers Company

Lead Sponsor

Trials

35

Recruited

7,200+

Published Research Related to This Trial

Stereotactic body radiation therapy (SBRT) for localized prostate cancer showed a high two-year biochemical relapse-free survival rate of 99%, indicating its efficacy in controlling the disease.

The treatment was well tolerated, with low rates of gastrointestinal (1%) and genitourinary (31%) toxicities, and most patients who were sexually potent before treatment maintained their potency two years later.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer: the Georgetown University experience. Chen, LN., Suy, S., Uhm, S., et al.[2022]

In a study of 84 low-risk prostate cancer patients treated with Stereotactic Ablative Body Radiotherapy (SABR), long-term quality of life (QOL) outcomes were generally positive, with a median follow-up of 50.8 months, although some patients reported declines in urinary (17.9%), bowel (26.2%), and sexual (37.5%) QOL domains.

Dosimetric factors such as rectal D1cc and penile bulb V35 were identified as significant predictors of worse QOL, highlighting the importance of adhering to strict dosimetric constraints to minimize side effects from treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy. Elias, E., Helou, J., Zhang, L., et al.[2018]

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 228 hormone-naïve patients with localized prostate cancer treated with SBRT, urinary and bowel functions showed only transient declines, returning to near baseline levels by 2 years post-treatment, indicating that SBRT is well tolerated.

However, sexual dysfunction progressively worsened over the 2 years following SBRT without recovery, highlighting the need for patients to be informed about potential long-term sexual side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes following stereotactic body radiation therapy for clinically localized prostate cancer. Bhattasali, O., Chen, LN., Woo, J., et al.[2022]

Stereotactic body radiotherapy (SBRT) is shown to be safe and effective for treating node-positive prostate cancer, with a median follow-up of 30 months revealing no severe gastrointestinal toxicities and manageable genitourinary side effects.

In a study of 60 patients, SBRT resulted in a 3-year overall survival rate of 89% and a biochemical failure-free survival rate of 77%, indicating promising long-term outcomes even in patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Ultra-hypofractionation in Node-positive Prostate Cancer. Telkhade, T., Murthy, V., Kanala, TS., et al.[2021]

In a study of 87 men with oligometastatic prostate cancer treated with stereotactic ablative radiotherapy (SABR), the median disease-free survival (DMFS) was 21.8 months for hormone-sensitive patients, indicating a significant benefit from this treatment.

Combining SABR with short-term androgen-deprivation therapy improved both biochemical progression-free survival (bPFS) and DMFS in patients with oligorecurrent hormone-sensitive prostate cancer, suggesting a potential strategy for enhancing treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival Outcomes and Pattern of Relapse After SABR for Oligometastatic Prostate Cancer. Mercier, C., Claessens, M., De Troyer, B., 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 258 patients with localized prostate cancer treated with SABR (Stereotactic Ablative Body Radiotherapy), significant dosimetric predictors for late toxicity and quality of life (QOL) were identified, particularly focusing on high-dose regions in the bladder and rectum.

The analysis revealed that avoiding high doses in the bladder and rectum is crucial, as bladder V38 was a significant predictor of QOL, while rectal Dmax, V38, and bladder D2cc were key predictors of late toxicity, emphasizing the importance of careful dose planning in SABR treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric predictors of toxicity and quality of life following prostate stereotactic ablative radiotherapy. Alayed, Y., Davidson, M., Quon, H., et al.[2021]

In a study of 26 patients with low- or intermediate-risk prostate adenocarcinoma, stereotactic body radiation therapy (SBRT) showed excellent biochemical control with no observed failures after a median follow-up of 59.5 months.

The treatment resulted in manageable late toxicity, with only 11.5% of patients experiencing significant genitourinary or gastrointestinal side effects, and patient-reported quality of life remained stable compared to pre-treatment levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial. Maas, JA., Dobelbower, MC., Yang, ES., et al.[2023]

A single session of stereotactic ablative body radiotherapy (SABR) for oligometastatic prostate cancer was found to be feasible and safe, with only one significant adverse event (a vertebral fracture) reported among 33 patients over a 2-year follow-up period.

The treatment resulted in high local progression-free survival rates of 97% at 1 year and 93% at 2 years, with nearly half of the patients (48%) avoiding the need for androgen deprivation therapy at the 2-year mark, indicating effective disease control and maintained quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Abative Body Radiotherapy (SABR) for Oligometastatic Prostate Cancer: A Prospective Clinical Trial. Siva, S., Bressel, M., Murphy, DG., et al.[2022]

In a study of 50 prostate cancer patients treated with MRI-guided adaptive radiotherapy (MRgRT) using ultra-hypofractionation, the treatment was well tolerated, with manageable acute genitourinary toxicity rates of 28% for Grade 1 and 36% for Grade 2, and very low gastrointestinal toxicity.

MRgRT allows for real-time tracking and adaptive planning during stereotactic body radiotherapy (SBRT), suggesting it is a promising method for delivering effective treatment with an acceptable safety profile for localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance image-guided adaptive stereotactic body radiotherapy for prostate cancer: preliminary results of outcome and toxicity. Ugurluer, G., Atalar, B., Zoto Mustafayev, T., et al.[2022]

Stereotactic ablative radiation (SAbR) at a dose of 45 Gy in 5 fractions shows a promising safety profile for treating localized prostate cancer, with acute urinary and gastrointestinal toxicity rates of 20.4% and 7.3%, respectively, and low rates of late toxicity after 2 years.

The treatment demonstrated excellent efficacy, with a biochemical failure-free survival rate of 100% at 1 year and 98.7% at 2 years, indicating strong disease control outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer. Chen, L., Gannavarapu, BS., Desai, NB., et al.[2022]

Stereotactic ablative body radiation (SABR) is a promising non-invasive treatment for localized prostate cancer, showing similar efficacy to brachytherapy in terms of disease control and lower side effects, making it a potentially safer option.

SABR is also more cost-effective and resource-efficient compared to traditional radiation techniques, but further well-powered studies are needed to confirm its benefits before it can be considered standard care, especially for patients with metastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy in patients with prostate cancer. Loblaw, A., Liu, S., Cheung, P.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5638714/

Stereotactic radiotherapy for prostate cancer: A review and ... We conclude that initial studies examining the use of SBRT in the treatment of prostate cancer have demonstrated impressive rates of biochemical recurrence-free ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6043737/

Stereotactic ablative body radiotherapy in patients with ... Efficacy for SABR appears to be similar to brachytherapy including positive biopsy rates 2–3 years post treatment, biochemical failure (BF) rates out to 10-year ...

3. 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 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2405632424000209

Stereotactic body radiation therapy (SBRT) for prostate ... Dose-fractionation sensitivity of prostate cancer deduced from radiotherapy outcomes of 5,969 patients in seven international institutional datasets: α/β = 1.4 ...

5. redjournal.org redjournal.org/article/S0360-3016(24)03368-6/abstract

Stereotactic Radiation Therapy for Localized Prostate Cancer SABR shows excellent long-term disease control for low- and intermediate-risk localized prostate cancer. Patients treated for prostate cancer ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06325046?term=John

Adaptive Radiation Therapy (ART) Stereotactic Ablative ... Shorter duration near margin-less ART may be just as effective at treating patients with localized prostate cancer but have less quality of life side effects ...

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

Online adaptive stereotactic body radiotherapy for ... The primary outcome measure is urogenital toxicity grade ≥ 3 within 3 months after completion of SBRT (according to CTCAE V5.0) or treatment- ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7761604/

Ablative Radiotherapy in Prostate Cancer: Stereotactic Body ... The authors found that the cumulative rates of worst RTOG grade ≥ 2 GI toxicities exceeding baseline were 9.3% vs. 13.2% (SBRT vs. control arm), ...