Reduced-Dose SABR for Prostate Cancer

(POTEN-C Trial)

Recruiting at 7 trial locations

Overseen By Sarah Neufeld

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Texas Southwestern Medical Center

Must not be taking: ADT, Anti-androgens

Disqualifiers: Metastatic disease, Severe comorbidity, 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

Compensation: Varies

Number of Visits: 5

Duration: 5 weeks

124 Participants Needed

Trial Summary

What is the purpose of this trial?

Reduction of dose to or 'sparing' of neurovascular structures during stereotactic ablative body radiotherapy (SAbR) for localized prostate cancer will improve retention of sexual potency, while retaining excellent oncologic control and other secondary health-related quality of life (HRQOL) endpoints. Primary Objectives: • To compare the decline in patient health-related quality of life (HRQOL) instrument-defined erectile dysfunction following stereotactic ablative body radiotherapy (SAbR) with or without neurovascular sparing Secondary Objectives: * Assess acute (within 3 months of treatment) and chronic (\>3 months after treatment) SAbR related GU and GI toxicities, as well as serial impact on HRQOL metrics over time * Assess biochemical progression free survival, local recurrence, distant recurrence, and survival * Evaluate simplified 'practical' secondary HRQOL sexual potency endpoints that can be compared to prior literature. Exploratory Objectives: * Evaluate feasibility of MRI BOLD/TOLD to be integrated as hypoxia monitoring sequences to standard already planned diagnostic and/or treatment planning MRI on the study in five patient pilot. * Evaluate quality of spacer placement and its effect on dose to neurovascular structures * Evaluate rate local recurrence in the area of sparing adjacent to the neurovascular elements by biopsy in those with biochemical progression.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like ADT (androgen deprivation therapy) or anti-androgen therapy are not allowed at the time of registration, and there are specific time frames for when PSA tests should not be done after stopping medications like finasteride or dutasteride.

What data supports the effectiveness of the treatment Reduced-Dose SABR for Prostate Cancer?

Research shows that Stereotactic Ablative Body Radiation (SABR) is a precise and non-invasive treatment for prostate cancer, delivering effective doses similar to other radiation methods with fewer side effects. It is well-tolerated and may delay further treatment, making it a promising option for prostate cancer management. ^{1 2 3 4 5}

Is reduced-dose SABR for prostate cancer safe for humans?

Stereotactic Ablative Body Radiotherapy (SABR) for prostate cancer is generally considered safe, with studies showing it has similar or lower side effects compared to other radiation treatments. It is well-tolerated and may have fewer side effects in the short term, although long-term safety data is still being gathered. ^{2 3 6 7 8}

How does the Reduced-Dose SABR treatment for prostate cancer differ from other treatments?

Reduced-Dose SABR (Stereotactic Ablative Body Radiotherapy) for prostate cancer is unique because it uses a lower dose of 30Gy, compared to higher doses like 45Gy, to deliver high-precision radiation in fewer sessions. This approach aims to minimize side effects while maintaining effectiveness, making it a potentially more convenient and cost-effective option compared to traditional radiation therapies. ^{2 3 8 9 10}

Eligibility Criteria

Men over 18 with localized prostate cancer, good performance status, and a desire to retain sexual function. They must have a PSA ≤20 ng/ml, prostate volume ≤80 grams without severe urinary symptoms or prior treatments for prostate cancer. Participants need an adequate testosterone level and no evidence of metastatic disease.

Inclusion Criteria

My prostate cancer has a Gleason score of 7 or less.

EPIC sexual domain composite score 60-100

I am 18 years old or older.

Exclusion Criteria

My MRI shows disease very close to major nerves and blood vessels.

History of significant psychiatric illness

More than half of my biopsy samples tested positive for cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive stereotactic ablative body radiotherapy (SAbR) with or without neurovascular sparing for localized prostate cancer

5 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety, effectiveness, and quality of life outcomes after treatment

24 months

Long-term follow-up

Participants are followed for biochemical progression free survival, local recurrence, distant recurrence, and overall survival

60 months

Treatment Details

Interventions

• 30Gy (Gray) planning target volume (PTV)

Trial Overview The trial is testing whether sparing neurovascular structures during stereotactic ablative body radiotherapy (SAbR) for localized prostate cancer helps maintain erectile function better than standard SAbR, while still providing effective cancer control.

Participant Groups

Group I: SAbR WITH Neurovascular sparing Experimental Treatment 1 Intervention

* GTV represents MR defined dominant radiographic disease, if identifiable. * CTV encompasses the full prostate. At physician's discretion, the insertion of the seminal vesicle upon the prostate on slices containing prostate may be included. * PTV1_30Gy represents a 3mm expansion on the CTV, excluding the neurovascular structures on the side to be spared (left or right). PTV1 will receive 6 Gy per fraction for 5 fractions (30 Gy). * PTV2_SAbR40Gy OR PTV2_SAbR45Gy will be generated by subtracting a 5mm expansion around the neurovascular elements to be spared (at least one side, left or right) from PTV1. These neurovascular structures consist of the neurovascular bundle, penile bulb, and internal pudendal arteries (see 4.1.5.2.16). PTV2 will receive 8-9 Gy per fraction for 5 fractions (40-45 Gy).

Group II: SAbR WITHOUT Neurovascular sparing Active Control 1 Intervention

* GTV represents MR defined dominant radiographic disease, if identifiable. * CTV encompasses the full prostate. At physician's discretion, the insertion of the seminal vesicle upon the prostate on slices containing prostate may be included. * PTV1_30Gy will not be used or created on this arm * PTV2_SAbR40Gy OR PTV2_SAbR45Gy will be generated by a 3mm expansion on the CTV. PTV2_SAbR will receive 8-9 Gy per fraction for 5 fractions (40-45 Gy).

Who Is Running the Clinical Trial?

University of Texas Southwestern Medical Center

Lead Sponsor

Trials

1,102

Recruited

1,077,000+

Boston Scientific Corporation

Industry Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

Findings from Research

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]

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]

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 comparing two SABR treatments for prostate cancer, patients receiving 40 Gy (pHART6) had similar biochemical relapse-free survival rates to those receiving 35 Gy (pHART3), indicating that higher doses do not compromise effectiveness over time.

However, patients in the pHART6 group experienced a higher incidence of grade 2 genitourinary and gastrointestinal toxicities, suggesting that while the treatment is effective, it may come with increased side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-escalation of five-fraction SABR in prostate cancer: Toxicity comparison of two prospective trials. Musunuru, HB., Quon, H., Davidson, M., et al.[2018]

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]

Stereotactic ablative body radiotherapy (SABR) is an advanced treatment that delivers high doses of radiation in fewer sessions while protecting surrounding healthy tissues, making it effective for small tumors in various locations, including the prostate.

SABR is becoming a standard treatment for low and intermediate-risk prostate cancer, supported by research from Sunnybrook and the US prostate SABR consortium, highlighting its efficacy in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of hypofractionated accelerated radiotherapy for prostate cancer - the sunnybrook experience. Musunuru, HB., Cheung, P., Loblaw, A.[2022]

References

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

Dose escalation improves cancer-related events at 10 years for intermediate- and high-risk prostate cancer patients treated with hypofractionated high-dose-rate boost and external beam radiotherapy. [2018]

2. China pubmed.ncbi.nlm.nih.gov

Stereotactic ablative body radiotherapy in patients with prostate cancer. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Dose-Intensified Stereotactic Ablative Radiation for Localized Prostate Cancer. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Consideration of the likely benefit from implementation of prostate image-guided radiotherapy using current margin sizes: a radiobiological analysis. [2021]

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

Radiation therapy margin reduction for patients with localized prostate cancer: A prospective study of the dosimetric impact and quality of life. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Dosimetric predictors of toxicity and quality of life following prostate stereotactic ablative radiotherapy. [2021]

7. Ireland pubmed.ncbi.nlm.nih.gov

Dose-escalation of five-fraction SABR in prostate cancer: Toxicity comparison of two prospective trials. [2018]

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

Dosimetric and patient correlates of quality of life after prostate stereotactic ablative radiotherapy. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Dosimetric impact of organ at risk daily variation during prostate stereotactic ablative radiotherapy. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Evolution of hypofractionated accelerated radiotherapy for prostate cancer - the sunnybrook experience. [2022]