Proton Radiation Therapy for Prostate Cancer

(PR11 Trial)

Overseen By Intake Coordinator

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: University of Florida

Must be taking: Androgen deprivation therapy

Must not be taking: Anticoagulants

Disqualifiers: T4 prostate, Metastasis, Prior prostate treatment, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether proton radiation, a specific type of radiation therapy, effectively treats high-risk prostate cancer. It targets prostate areas identified by MRI scans to deliver higher doses of radiation in a shorter time. Participants should be men diagnosed with high-risk prostate cancer who have visible tumors on MRI scans. The goal is to determine if this approach can better manage the cancer and reduce recurrence. As an unphased trial, this study allows participants to contribute to innovative research that could lead to improved 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 exclude people who are currently taking certain blood thinners like warfarin, heparin, and others. It's best to discuss your specific medications with the trial team.

What prior data suggests that this proton radiation therapy is safe for treating high-risk prostate cancer?

Research shows that proton radiation therapy is generally well-tolerated by patients with prostate cancer. Studies have found that patients treated with proton therapy have a lower chance of developing new cancers compared to those receiving other types of radiation, indicating that proton therapy is generally safe.

One study found that men with prostate cancer who received proton therapy along with a small extra dose of radiation had their cancer well-controlled and experienced few side effects. Most patients did not suffer from severe side effects due to the treatment.

Overall, evidence suggests that proton therapy is a safe option for treating prostate cancer, with many patients experiencing few side effects and effective cancer control. However, as with any treatment, individual experiences may vary, and it is important to discuss potential risks and benefits with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments, HR-A and HR-B, because they utilize proton radiation therapy, which offers a more precise targeting of prostate cancer compared to conventional radiation therapies like X-rays. Unlike traditional methods, proton therapy delivers high doses of radiation directly to the tumor with minimal exposure to surrounding healthy tissues, potentially reducing side effects. This precision is especially crucial for treating sensitive areas like the prostate and seminal vesicles. By reducing damage to nearby organs, these treatments aim to improve patient quality of life and outcomes.

What evidence suggests that this trial's treatments could be effective for high-risk prostate cancer?

This trial will compare two approaches to proton radiation therapy for high-risk prostate cancer: HR-A and HR-B. Research has shown that proton radiation therapy holds promise for treating prostate cancer, particularly in high-risk cases. Studies have found it to be at least as effective as traditional radiation methods. Proton therapy often causes fewer severe side effects related to urinary and digestive functions. In one study, patients who received proton therapy lived longer than those who underwent other types of radiation. This suggests that proton therapy could be a strong option for managing high-risk prostate cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Curtis M Bryant, MD, MPH

Principal Investigator

University of Florida Health Proton Therapy Institute

Are You a Good Fit for This Trial?

Men over 18 with high-risk prostate cancer, who haven't had previous local treatments or pelvic radiation. They must have a visible tumor on MRI, no distant metastasis or positive lymph nodes, and be able to start treatment within 16 weeks of signing up. Participants should not have severe heart failure, end stage renal disease, inflammatory bowel diseases affecting the rectum, or recent major intrapelvic surgery.

Inclusion Criteria

I have been mostly active and able to carry out all pre-disease activities without restriction in the last 4 months.

Hemoglobin must be ≥ 10 g/ml within 4 months prior to registration

Patient must give study-specific informed consent on an IRB-approved consent prior to any research related procedures or study treatment

Exclusion Criteria

My prostate size changed by more than 25% since my last MRI, and I need another MRI.

Patients with positive nodes on cross-sectional imaging

I have an active inflammatory bowel condition affecting my rectum.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Androgen Deprivation Therapy (ADT)

ADT is started 8-10 weeks prior to radiation and continued for a total of 18 months

18 months

Radiation Therapy

Dose-escalated proton radiation therapy delivered over 8-9 weeks with a simultaneous integrated boost to the MRI identified intraprostatic tumor

8-9 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of biochemical failure, local recurrence, and overall survival

5 years

What Are the Treatments Tested in This Trial?

Interventions

• HR-A
• HR-B

Trial Overview The trial is testing if dose-escalated proton radiation therapy can better treat high-risk prostate cancer. It involves hypofractionation and an integrated boost targeting the tumor identified by MRI over 8-9 weeks. Androgen deprivation therapy may also be used for 18 months.

How Is the Trial Designed?

Group I: HR-B (High-risk B) Experimental Treatment 1 Intervention

* Prostate, proximal seminal vesicles, and pelvic nodes: 2 cobalt gray equivalent per fraction to a total does of 46 cobalt gray equivalent. * Prostate and proximal seminal vesicles: 2 cobalt gray equivalent per fraction to a total dose of 32 cobalt gray equivalent. * Entire uninvolved seminal vesicle when part of the seminal vesicle is involved with tumor: 2 cobalt gray equivalent per fraction to a total dose of 78 cobalt gray equivalent. * Simultaneous integrated boost to the IPT: 2.2 cobalt gray equivalent per fraction to a total dose of 85.8 cobalt gray equivalent.

Group II: HR-A (High-risk A) Experimental Treatment 1 Intervention

* Prostate and proximal seminal vesicles: 2 cobalt gray equivalent per fraction to a total dose of 78 cobalt gray equivalent. * Simultaneous integrated boost to the IPT: 2.2 cobalt gray equivalent per fraction to a total dose of 85.8 cobalt gray equivalent.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Published Research Related to This Trial

In a study of 192 patients treated with proton beam therapy for prostate cancer, the rate of grade 2 or higher gastrointestinal toxicity was 21.3%, primarily manifesting as rectal bleeding, but severe toxicity (grade 3 or higher) was rare.

Patient-reported quality of life regarding bowel function remained high throughout the 2-year follow-up, with median EPIC bowel domain scores only slightly decreasing from pretreatment to 2 years post-treatment, indicating that proton beam therapy is generally safe and well-tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of Gastrointestinal Toxicity in Patients Receiving Proton Beam Therapy for Prostate Cancer: A Single-Institution Experience. Lee, HJ., Macomber, MW., Spraker, MB., et al.[2022]

In a study of 423 men treated with proton beam therapy (PBT) for prostate cancer, the 5.2-year follow-up showed an impressive overall survival rate of 99.8% and a disease-specific survival rate of 100%, indicating high efficacy of this treatment.

While acute toxicity was relatively low, with no severe grade ≥3 complications, there was a modest but clinically significant decrease in bowel quality of life scores after treatment, suggesting that while PBT is effective, it may still impact certain aspects of quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy for Localized Prostate Cancer: Results from a Prospective Quality-of-Life Trial. Pugh, TJ., Choi, S., Nogueras-Gonzalaez, GM., et al.[2022]

Proton radiation therapy is gaining popularity for localized prostate cancer due to its ability to deliver high doses to the tumor while minimizing damage to surrounding healthy tissue, thanks to the unique Bragg peak effect.

While proton therapy has shown effectiveness in dose escalation for prostate cancer, it currently lacks clear dosimetric superiority over traditional X-ray intensity-modulated radiation therapy, although advancements in techniques like pencil-beam scanning may enhance its benefits in the future.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton radiation for localized prostate cancer. Coen, JJ., Zietman, AL.[2021]

In a study of 215 prostate cancer patients treated with image-guided accelerated hypofractionated proton therapy, the 5-year rates of freedom from disease progression were very high, at 95.9% overall, indicating strong efficacy of this treatment approach.

The treatment resulted in minimal severe toxicities, with only 0.5% experiencing significant gastrointestinal issues and 1.7% facing severe urologic toxicities, suggesting that this therapy is safe for selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-year outcomes from a prospective trial of image-guided accelerated hypofractionated proton therapy for prostate cancer. Henderson, RH., Bryant, C., Hoppe, BS., et al.[2018]

In a study of 582 prostate cancer patients treated with moderately accelerated hypofractionated proton therapy (AHPT), the 5- and 7-year rates of freedom from biochemical progression were very high, at 96.8% and 95.2% overall, indicating strong long-term efficacy of this treatment.

The treatment was associated with minimal toxicities, with low rates of grade 2 gastrointestinal (9.9% at 5 years) and grade 3 genitourinary (1.3% at 5 years) side effects, and no severe toxicities (grade ≥4) reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five- and seven-year outcomes for image-guided moderately accelerated hypofractionated proton therapy for prostate cancer. Henderson, RH., Bryant, CM., Nichols, RC., 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 289 prostate cancer patients, hypofractionated proton beam therapy (PBT) showed no significant differences in acute adverse event rates or quality of life, as measured by the International Prostate Symptom Score (IPSS), compared to conventionally fractionated PBT.

The study evaluated patients treated with different doses (2.0, 2.5, and 3.0 Gy RBE per fraction) and found that factors like diabetes, age, and androgen deprivation therapy did not influence the IPSS outcomes, suggesting that hypofractionated PBT is a safe option without increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer. Iizumi, T., Ishikawa, H., Sekino, Y., et al.[2022]

In a study of 180 prostate cancer patients treated between 1972 and 1979, those receiving a proton beam boost along with conventional x-ray therapy were able to receive a higher dose to the tumor without increasing side effects, demonstrating the safety of this approach.

Despite the increased dose delivered to the tumor using the proton beam, there were no significant differences in patient survival, disease-free survival, or local recurrence-free survival compared to those treated with conventional x-ray therapy, suggesting similar efficacy between the two methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protons or megavoltage X-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison. Duttenhaver, JR., Shipley, WU., Perrone, T., et al.[2019]

In a study of 211 prostate cancer patients treated with image-guided proton therapy, early outcomes showed high efficacy with only 1.9% experiencing Grade 3 genitourinary (GU) symptoms and less than 0.5% experiencing Grade 3 gastrointestinal (GI) toxicities after a minimum follow-up of 2 years.

The need for pretreatment GU symptom management was linked to higher rates of posttreatment GU symptoms, indicating that managing symptoms before therapy may help reduce complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early outcomes from three prospective trials of image-guided proton therapy for prostate cancer. Mendenhall, NP., Li, Z., Hoppe, BS., et al.[2022]

Proton therapy has been used for decades in treating prostate cancer, and advancements like pencil-beam scanning have improved its application, but the clinical benefits compared to traditional treatments are still unclear.

A randomized trial is underway to compare proton beam therapy with intensity-modulated radiotherapy for early-stage prostate cancer, which will help clarify the effectiveness and role of proton therapy in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical controversies: proton therapy for prostate cancer. Mouw, KW., Trofimov, A., Zietman, AL., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8489490/

Consensus Statement on Proton Therapy for Prostate Cancer Because of the relative biologic effectiveness (RBE) of proton therapy, it is predicted to be at least as effective in treating cancer as photon-based radiation ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2405630824000995

Proton therapy toxicity outcomes for localized prostate cancer Proton therapy is associated with low rates of late high grade genitourinary and gastrointensity toxicity for the treatment of localized prostate cancer.

3. academic.oup.com academic.oup.com/jrr/article/66/1/39/7954234

Real-world comparative outcomes and toxicities after ... This retrospective study aimed to compare the clinical outcomes of intensity-modulated radiation therapy (IMRT) and proton beam therapy (PBT). A ...

4. redjournal.org redjournal.org/article/S0360-3016(24)03237-1/fulltext

Phase III Randomized Clinical Trial of Proton Therapy vs. ... Proton beam therapy (PBT) has certain dosimetric advantages with the potential to reduce treatment-associated morbidity and improve oncologic ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03624660

Dose-Escalated Proton Radiation Therapy for High-Risk ... The purpose of this research study is to determine if dose-escalated proton radiation therapy is a good way to treat high-risk prostate cancer.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1538472125000017

Safety and early outcomes of proton therapy and low-dose ... At 45 months' follow-up time, treatment with PT and LDR boost led to high control rates and low toxicity for men with prostate cancer.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2331518023000136

Case-Matched Outcomes of Proton Beam and Intensity ... The data from 334 patients treated with conventionally fractionated (79.2 GyRBE in 44 fractions) PBT or IMRT were retrospectively analyzed.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7528218/

Comparison of outcomes and toxicities among radiation ... Differences in overall survival, distant metastasis, and cancer specific mortality (5-year rates: 82–97%, 1–14%, 0–8%, respectively) have not been detected in ...

9. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.709530/full

Clinical Efficacy and Safety of Proton and Carbon Ion ... A random-effect meta-analysis indicated that the 3-, 4-, 5-year OS was 97% (95% CI, 96–98%), 87% (85–89%), 92% (95% CI, 87–97%), respectively ( ...