Proton SBRT for Prostate Cancer

Overseen By Ryan Holder, BS

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: The New York Proton Center

Disqualifiers: Prior prostate surgery, Chronic prostatitis, Urethral stricture, Active cancer, 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: 11

Duration: 2 weeks

61 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a single arm phase II study of image-guided pencil beam scanning proton SBRT (40Gy RBE in 5 fractions delivered every other day) for patients with low- and intermediate-risk prostate cancer. The primary aim is to assess GU/GI toxicity of proton SBRT and compare this to historic outcomes associated with photon-based prostate SBRT. The primary endpoint is 2-year grade 3+ GU/GI toxicity free rate by CTCAE v5.0, which is expected to be ≥95%. Toxicity will be evaluated by the treating radiation oncologist at least once during SBRT, then following SBRT at 1, 3, 6, 12, 18, and 24 months. The treatment will be considered safe if grade 3 or higher GU/GI toxicity free rate at 2 years is \>85% (95% rate expected with a 10% non-inferiority margin). The accrual goal is 61 patients over 3 years. To ensure that unexpected significant toxicity is identified, all grade 3 or higher toxicities will be reported to the study PI and the trial will stop accruing if at any point 4 or more patients experience a grade 3 or higher toxicity after completing SBRT. This is felt to be conservative given the vast experience with photon SBRT at this dose with an expected G3+ toxicity of \~5%. Secondary objectives are to examine patient-reported urinary, gastrointestinal, sexual, and financial outcomes using IPSS, EPIC-26, and COST questionnaires at the same follow-up timepoints as above. Baseline measures of these domains will be obtained prior to treatment as well. Clinical outcomes will also be evaluated with PSA measured at each follow-up, as well as prostate MRI and biopsies at 2 years. Patients will be followed for at least 2 years to determine rates of PSA relapse, salvage treatment, development of metastases, death from prostate cancer, and overall survival. A dosimetric comparison will be performed where each patient will be planned for proton and photon SBRT to determine possible advantages of proton SBRT.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Pencil Beam Scanning Proton SBRT for prostate cancer?

Research shows that Pencil Beam Scanning (PBS) proton therapy can effectively target prostate cancer while sparing nearby healthy tissues, and it has been found to have acceptable target coverage and minimal cold spots in treatment plans. Additionally, PBS may offer dosimetric benefits over other proton therapy methods, potentially leading to reduced toxicity. ^{1 2 3 4 5}

Is Proton SBRT safe for treating prostate cancer?

Studies show that Proton SBRT, including Pencil Beam Scanning, is generally safe for treating prostate cancer, with manageable side effects and no severe long-term toxicity reported. ^{3 6 7 8 9}

How is Pencil Beam Scanning Proton SBRT different from other prostate cancer treatments?

Pencil Beam Scanning Proton SBRT is unique because it uses a highly precise form of proton therapy that targets prostate cancer with minimal damage to surrounding tissues, thanks to advanced techniques like Monte Carlo dose calculations and hydrogel rectal spacers. This approach can lead to better patient-reported quality of life and lower rates of severe side effects compared to traditional radiation therapies. ^{1 5 10 11 12}

Research Team

Daniel Gorovets, MD

Principal Investigator

The New York Proton Center

Shaakir Hasan, DO

Principal Investigator

The New York Proton Center

Eligibility Criteria

Men over 18 with low or intermediate-risk prostate cancer, a Gleason score ≤7, PSA ≤20 ng/ml, and no prior major prostate surgery. They must have a life expectancy of more than 2 years and be able to follow up for at least that time. Participants need an IPSS score ≤20, KPS ≥80%, and agree to specific procedures like fiducial marker placement.

Inclusion Criteria

I am a man aged 18 or older.

My prostate is smaller than 100 cc, confirmed by MRI or CT scan.

IPSS ≤ 20

Exclusion Criteria

I have had chronic prostatitis or a narrowed urethra in the past.

Your doctor estimates that you have less than 2 years to live.

I don't have active cancer, except for non-serious skin cancers, and my doctor thinks I'm unlikely to relapse soon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pencil beam scanning proton SBRT (40Gy RBE in 5 fractions delivered every other day)

2 weeks

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with evaluations at 1, 3, 6, 12, 18, and 24 months

24 months

6 visits (in-person)

Treatment Details

Interventions

• Pencil Beam Scanning Proton SBRT

Trial Overview The trial is testing pencil beam scanning proton SBRT as a treatment for prostate cancer. It involves delivering radiation in five sessions every other day. The main goal is to see if this method causes less severe urinary or gastrointestinal side effects compared to traditional treatments after two years.

Participant Groups

Group I: Stereotactic body radiation therapy (SBRT) with Pencil Beam Scanning (PBS) proton therapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

The New York Proton Center

Lead Sponsor

Trials

3

Recruited

1,900+

Findings from Research

In a study of 304 men with localized prostate cancer, those treated with pencil beam scanning (PBS) showed a higher proportion of significant declines in urinary quality of life (QOL) compared to those treated with passive scatter/uniform scanning (PS/US) at 12 months, indicating a potential difference in outcomes between the two proton therapy methods.

However, overall average quality-of-life declines did not significantly differ between PBS and PS/US, suggesting that while there may be specific areas of concern, both treatment modalities have similar average effects on patient-reported outcomes over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient reported outcomes following proton pencil beam scanning vs. passive scatter/uniform scanning for localized prostate cancer: Secondary analysis of PCG 001-09. Mishra, MV., Khairnar, R., Bentzen, SM., et al.[2022]

Whole-pelvis pencil beam scanning (PBS) proton therapy is effective for treating prostate cancer, providing good target coverage while minimizing damage to surrounding organs at risk (OAR).

Two treatment planning approaches, conventional optimization (CO) and robust optimization (RO), were evaluated, with RO offering potential advantages in OAR sparing and efficiency, while CO remains a viable option for institutions lacking advanced capabilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust treatment planning in whole pelvis pencil beam scanning proton therapy for prostate cancer. Butala, AA., Ingram, WS., O'Reilly, SE., et al.[2021]

In a study comparing proton beam therapy (PBT) techniques for prostate cancer, acute gastrointestinal toxicity rates were similar between pencil beam scanning (PBS) and passive scattering/uniform scanning (PS/US), with rates of 2.9% and 2.1% respectively.

However, PBS was associated with significantly higher acute genitourinary toxicity (21.9% vs. 15.1% for PS/US), indicating a need for further investigation into the safety profiles of these treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy delivered using pencil beam scanning vs. passive scattering/uniform scanning for localized prostate cancer: Comparative toxicity analysis of PCG 001-09. Mishra, MV., Khairnar, R., Bentzen, SM., et al.[2022]

Stereotactic body proton therapy (SBPT) showed greater dose escalation potential compared to stereotactic body photon therapy (SBXT) in treating prostate cancer, particularly for larger prostate volumes, indicating it may be a more effective option for high-risk patients.

In a study of 25 patients, SBPT resulted in lower doses to critical structures like the bladder neck while still achieving significant target coverage, suggesting a safer treatment profile with potentially fewer side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simulation of an HDR "Boost" with Stereotactic Proton versus Photon Therapy in Prostate Cancer: A Dosimetric Feasibility Study. Remick, JS., Sabouri, P., Zhu, M., et al.[2022]

In a study of 192 prostate cancer patients treated with proton beam therapy (PBT) over a median follow-up of 1.7 years, only 5 patients experienced grade 3 toxicity, with no occurrences of grade 4 or 5 toxicity, indicating a high safety profile for this treatment.

Patient-reported outcomes showed stable urinary function post-treatment, while sexual health scores declined slightly at 1 year but did not worsen thereafter; bowel function scores also decreased but stabilized, suggesting manageable side effects associated with PBT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes. Lee, HJ., Macomber, MW., Spraker, MB., et al.[2019]

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 33 patients with localized prostate cancer treated with modern proton beam radiotherapy (PBT), there were no severe acute toxicities, indicating a high safety profile for this treatment method.

With a median follow-up of 18 months, the use of hydrogel rectal spacers and fiducial tracking without endorectal balloons resulted in minimal treatment-related toxicity and promising oncologic outcomes, although late erectile dysfunction was noted as a common issue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Cancer Treatment with Pencil Beam Proton Therapy Using Rectal Spacers sans Endorectal Balloons. Forsthoefel, M., Hankins, R., Ballew, E., et al.[2022]

References

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

Patient reported outcomes following proton pencil beam scanning vs. passive scatter/uniform scanning for localized prostate cancer: Secondary analysis of PCG 001-09. [2022]

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

Robust treatment planning in whole pelvis pencil beam scanning proton therapy for prostate cancer. [2021]

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

The effects of motion on the dose distribution of proton radiotherapy for prostate cancer. [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Proton beam therapy delivered using pencil beam scanning vs. passive scattering/uniform scanning for localized prostate cancer: Comparative toxicity analysis of PCG 001-09. [2022]

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

Simulation of an HDR "Boost" with Stereotactic Proton versus Photon Therapy in Prostate Cancer: A Dosimetric Feasibility Study. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

5-Years Analysis of Effectivity and Toxicity of Ultra-Hypofractionated Proton Radiotherapy in the Treatment of Low- and Intermediate-Risk Prostate Cancer-A Retrospective Analysis. [2023]

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

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes. [2019]

8. 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]

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

A dosimetric comparison of ultra-hypofractionated passively scattered proton radiotherapy and stereotactic body radiotherapy (SBRT) in the definitive treatment of localized prostate cancer. [2018]

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

Effect of intrafraction prostate motion on proton pencil beam scanning delivery: a quantitative assessment. [2018]

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

Prostate Cancer Treatment with Pencil Beam Proton Therapy Using Rectal Spacers sans Endorectal Balloons. [2022]

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

Impact of intrafraction and residual interfraction effect on prostate proton pencil beam scanning. [2018]