SBRT for Prostate Cancer

(PREPARE SBRT Trial)

Overseen By Pragya Yadav, Ph.D.

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Weill Medical College of Cornell University

Disqualifiers: Pelvic radiotherapy, Inflammatory bowel disease, others

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

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to radiation therapy for men with aggressive prostate cancer, specifically those with a Gleason Score of 8 or higher or evidence of advanced disease. The goal is to identify the safest and most effective radiation dose by exploring different levels, a process known as dose escalation. Only men with prostate cancer who have not previously undergone pelvic radiation and are fit for surgery qualify as candidates. Participants will help researchers understand how different doses impact cancer and side effects.

As an unphased trial, participation offers a unique opportunity to contribute to pioneering research in radiation therapy for aggressive prostate cancer.

Do I have to stop taking my current medications for the trial?

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 prior data suggests that this dose escalation is safe for prostate cancer patients?

Research has shown that SBRT (Stereotactic Body Radiotherapy) with doses between 32.5 and 40 Gy usually carries a low risk of moderate or severe side effects. Most people do not experience serious problems from this treatment. Studies also suggest that higher doses of SBRT can control the disease more effectively.

In trials, small groups of patients begin with lower doses. If they do not experience serious side effects, the dose increases for the next group. This process helps identify the safest dose that remains effective.

Overall, SBRT is generally well-tolerated, but monitoring for side effects, especially at higher doses, remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the use of SBRT (Stereotactic Body Radiation Therapy) for prostate cancer because it offers a more targeted and efficient approach to treatment. Unlike traditional radiation therapies that require multiple sessions over several weeks, SBRT delivers higher doses of radiation in just a few sessions, potentially reducing treatment time and improving patient convenience. This dose escalation study aims to fine-tune the optimal radiation levels to maximize effectiveness while minimizing side effects. By focusing on precise radiation delivery, SBRT could lead to fewer side effects and better outcomes for patients with prostate cancer.

What evidence suggests that this dose escalation is effective for prostate cancer?

Research has shown that stereotactic body radiotherapy (SBRT) is promising for prostate cancer. One study found that administering a total dose of 36.25 Gy over five sessions successfully prevented cancer progression in 96% of patients over three years. Other studies with SBRT doses between 32.5 and 40 Gy reported that patients tolerated the treatment well and experienced better outcomes without serious side effects. Data from five-year follow-ups also demonstrated excellent results, comparable to other effective prostate cancer treatments. This trial will explore dose escalation within SBRT, testing doses of 5 Gy, 6 Gy, and 6.5 Gy to determine the recommended phase II dose. These findings suggest that SBRT, even at higher doses, effectively treats prostate cancer with minimal side effects. ^{2 4 6 7 8}

Who Is on the Research Team?

Silvia C. Formenti, M.D.

Principal Investigator

Weill Cornell Medicine - New York Presbyterian Hospital

Are You a Good Fit for This Trial?

The PREPARE SBRT trial is for men over 18 with high-risk prostate cancer, confirmed by a Gleason Score of 8+ or evidence of advanced disease (T3). Participants must be fit for surgery, have no prior pelvic radiotherapy, and not currently treated for inflammatory bowel disease. They need to have clear bone scans and MRI/CT scans without significant nodal involvement.

Inclusion Criteria

Patient can undergo an MRI.

I am mostly able to care for myself and carry out daily activities.

I am a man over 18 with confirmed prostate cancer.

Exclusion Criteria

I am currently being treated for inflammatory bowel disease.

I have had radiation therapy to my pelvic area before.

I do not want to have surgery to remove my prostate.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive stereotactic body radiotherapy (SBRT) with dose escalation and de-escalation to determine the recommended phase II dose

1 week

5 visits (in-person)

Surgery

Participants undergo radical prostatectomy after SBRT

1 month

Follow-up

Participants are monitored for acute toxicity and quality of life scores after treatment

3 months

Long-term follow-up

Participants' quality of life scores are collected over an extended period

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Dose escalation

Trial Overview This study tests the effects of increasing doses of stereotactic body radiotherapy (SBRT) before prostate removal surgery in men with aggressive prostate cancer. The goal is to see if higher radiation doses can better control the cancer when given before surgery.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

This is a modified dose escalation and de-escalation study with an expansion of 3 or 6 pts to allow the recommended phase II dose (RP2D) be examined in a total of 9 pts. The dose limiting toxicity (DLT) is defined as Grade 3 or higher toxicity related to preoperative radiotherapy according to the Clavien-Dindo Classification. 3 radiation dose levels, 5 Gy, 6 Gy and 6.5Gy are considered. At the start of each dose level, 3 pts will be enrolled and treated for five days. If none of the 3 pts develop the DLT, the testing dose will escalate to the next level. If 1 of the 3 pts develops the DLT, the current dose will be tested in an additional 3 pts. If no additional pts develop the DLT, the dose will escalate.

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

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 79 prostate cancer patients treated with virtual HDR SBRT, the median PSA level dropped significantly from 5.6 ng/mL to 0.05 ng/mL after 5 years, indicating effective cancer control.

The treatment resulted in a high 5-year biochemical-relapse-free survival rate of 100% for low-risk and 92% for intermediate-risk patients, with manageable toxicity levels, including only 6% experiencing late grade 3 GU toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations. Fuller, DB., Naitoh, J., Mardirossian, G.[2023]

In a study of 551 low- and intermediate-risk prostate cancer patients treated with high-dose stereotactic body radiotherapy (SBRT), the treatment was well tolerated, with only 1.8% experiencing acute gastrointestinal toxicities and 10% experiencing acute genitourinary toxicities.

The 5-year cumulative incidence of prostate-specific antigen (PSA) failure was low at 2.1%, and 88% of patients who underwent biopsies after treatment showed no residual active disease, indicating effective tumor control with this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Tolerance and Tumor Control Outcomes with High-dose Ultrahypofractionated Radiation Therapy for Prostate Cancer. Zelefsky, MJ., Pinitpatcharalert, A., Kollmeier, M., et al.[2021]

In a study of 24 patients with intermediate- and high-risk prostate cancer treated with dose-escalated stereotactic body radiation therapy (SBRT), the treatment showed a high 24-month prostate-specific antigen relapse-free survival rate of 95.8%.

The use of a high-dose avoidance zone (HDAZ) during SBRT resulted in low rates of acute and late genitourinary (GU) and gastrointestinal (GI) toxicities, with no severe (grade ≥3) toxicities reported, indicating a safe approach to dose escalation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Escalated Stereotactic Body Radiation Therapy for Patients With Intermediate- and High-Risk Prostate Cancer: Initial Dosimetry Analysis and Patient Outcomes. Kotecha, R., Djemil, T., Tendulkar, RD., et al.[2022]

Stereotactic body radiation therapy (SBRT) resulted in significantly lower post-treatment PSA levels compared to intensity-modulated radiation therapy (IMRT) at 2 and 3 years, indicating better efficacy in controlling prostate cancer.

Both SBRT and IMRT showed similar overall survival rates after 5 years, but SBRT offers advantages such as lower cost and easier application, making it a suitable alternative for treating localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Stereotactic body radiation therapy versus conventional intensity-modulated radiation therapy for the treatment of prostate cancer]. Gao, QN.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12380758/

Analysis of standard vs dose-escalated stereotactic body ... In a Phase II trial, localized SBRT (36.25 Gy/5 every other day) yielded promising outcomes. A 36-month follow-up showed a 96% 3-year bPFS rate, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7525798/

Five-Year Outcomes of a Phase 1 Dose-Escalation Study ... SBRT doses ranging from 32.5 to 40 Gy in 5 fractions were well tolerated without severe urinary or rectal toxicities. Biopsy outcomes suggest improved rates of ...

3. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)03546-1/abstract

5-year efficacy and toxicity in the hypo-FLAME trial Prostate SBRT with an integrated focal boost demonstrated excellent 5-year outcomes. The 5-year bDFS is comparable to that of the focal boosted FLAME-cohort.

4. redjournal.org redjournal.org/article/S0360-3016(21)00543-5/fulltext

Prostate SBRT Dose Escalation (9 Gy × 5, 13.3 Gy × 3, 24 ... The vast majority of clinical evidence for the use of SBRT is based on a 5-fraction regimen of 36.25 to 40 Gy, as is used in the 2 primary randomized trials ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301623004467

Toxicity and Patient-Reported Quality-of-Life Outcomes ... A prospective, phase 2, heterogeneous dose-escalation study reported similar acute toxicity to prior, lower-dose prostate SBRT studies while treating areas of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37949730/

Long-term Outcomes from a Phase 1 Dose Escalation ... Conclusions: SBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2588931123002353

Long-term Outcomes from a Phase 1 Dose Escalation ... SBRT doses ranging from 32.5 to 40 Gy were associated with low incidence of moderate or severe toxicities. Higher doses resulted in superior disease control ...

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2723641

Long-term Outcomes of Stereotactic Body Radiotherapy for ... This cohort study of pooled individual patient data assesses long-term outcomes after stereotactic body radiotherapy for low-risk and ...