Stereotactic Ablative Radiation Therapy for Prostate Cancer

Prostate Cancer Clinical Trial

— SUPR-SABR  

Official title:

Phase II Trial of Sparing the Urethra, Pudendal Artery and Rectum During Stereotactic Ablative Body Radiotherapy (SUPR-SABR) for Low and Intermediate Risk Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05668351
• Other study ID #: 103629
• Status: Recruiting
• Phase: N/A
• Start date: May 12, 2023
• Est. completion date: January 15, 2026

Study information

• Verified date: October 2023
• Source: Medical University of South Carolina
• Contact: Alan Brisendine
• Phone: 843-792-6382
• Email: brisend[@]musc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This single arm trial will investigate a novel way to plan and deliver SABR for prostate cancer. Prostate-directed SABR will be high-dose SABR (40 Gy in 5 fractions) with central sparing of the urethra and peripheral sparing of the rectum and pudendal arteries (SUPR-SABR). This study tests the hypothesis that genitourinary (GU) and gastrointestinal (GI) toxicity rates following SUPR-SABR are comparable to (or possibly lower than) historical GU and GI toxicity rates following standard SABR (stSABR) with 36.25 Gy in the treatment of low- and intermediate-risk prostate cancer.

Description:

It is estimated that there will be 268,000 prostate cancer diagnoses and nearly 35,000 deaths due to prostate cancer in the United States in 2022 [1]. Most men diagnosed with prostate cancer present with localized or organ confined disease which is most commonly managed with active surveillance, prostatectomy, brachytherapy, and external beam radiotherapy (EBRT). Conventionally fractionated (1.8-2.0 Gy per fraction for nine weeks) EBRT is of historical and clinical importance in localized prostate cancer, however, moderately hypofractionated (≥2.5 Gy per fraction for four to six weeks) EBRT and SABR have also emerged as standards of care in appropriately selected patients.

The increased precision associated with image guided stereotactic techniques now permits safe delivery of large doses per fraction, also known as hypofractionation. SABR is a specific type of hypofractionated RT. Hallmarks of the SABR technique, also commonly known as stereotactic body radiotherapy (SBRT), include doses of at least 5 Gy per fraction, five or fewer fractions, motion management, noncoplanar beam or arc therapy, body immobilization, and ablative prescription doses.

There is growing interest in the use of SABR in men with low- and intermediate- risk prostate cancer due to their lower risk of extra prostatic disease including pelvic lymph node micrometastases and the low alpha/beta ratio of prostate cancer. Several series with follow up times exceeding five years have demonstrated excellent biochemical control for SABR approaching 95% for low risk and 80-90% for intermediate risk disease with low rates of clinically significant late GU and GI toxicity. Most published clinical experiences of SABR for prostate cancer have employed 35 to 36.25 Gy in 7- to 7.25 Gy fractions (i.e., standard SABR or stSABR). Importantly, it has never been established whether this represents the optimal dose level for SABR and, nationally, there is not only a single standard of care for SABR prescription dose and fractionation. What is more, contemporary literature with prostate SABR suggests a benefit with dose escalation, however, there is interest in avoiding a parallel increase in GU, GI, and sexual side effects of treatment.

The proposed trial concept would offer men with low- and intermediate-risk prostate cancer a dose-escalated SABR regimen (SUPR-SABR) of 40 Gy in 5 fractions with a safety profile already supported by medical literature and which is expectedly more efficacious than stSABR. This dose and fractionation is already being used in some radiation oncology practices. However, to further improve the therapeutic index of curative RT, the protocol will employ all available methods to spare the urethra, pudendal artery, and rectum (SUPR-SABR): foley catheter placement during planning, rectal spacer gel placement, endorectal balloon during planning and treatment, prostatic immobilization, strict contouring and dose constraints, and the most highly conformal photon planning available. This protocol will offer men a clinical study with highly important endpoints and lower anticipated treatment related morbidity. If the primary analysis demonstrates favorable healthcare related quality of life (HRQOL) with SUPR-SABR when compared to prospectively collected historic controls of stSABR, then this would serve as the basis for a randomized trial between SUPR-SABR and stSABR.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: January 15, 2026
• Est. primary completion date: January 15, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for the duration of the study

3. Male patients aged 18 years and older

4. In good general health as evidenced by medical history to be a candidate for curative-intent prostate cancer treatment

5. Ability to receive pelvic radiotherapy and be willing to adhere to the SUPR-SABR regimen

6. Previously untreated prostate cancer (with cytotoxic chemotherapy, surgical or radiation therapy)

7. Localized adenocarcinoma of the prostate with the following features:

1. cT1-T2c

2. PSA<20

• Patients receiving a 5-alpha reductase inhibitor must have a PSA <10

3. Grade Group 1-3

8. Patient willing and able to complete the EPIC questionnaire at time of registration and 1-, 12-, and 24- months post treatment

9. Prostate volume <120 cc

10. History and physical including a digital rectal exam 90 days prior to registration

11. ECOG performance status 0-2

12. Be eligible and willing to undergo MRI prostate and pelvis as a component of RT planning

13. Bone and soft tissue imaging as clinically indicated (for unfavorable intermediate risk or symptomatic patients only) within 120 days prior to registration

14. IPSS score =20 at time of initial history and physical with treating radiation oncologist

Exclusion Criteria:

1. Female patients (due to lack of prostate gland)

2. Concurrent use of testosterone supplementation

3. Known homozygous for ATM pathogenic mutation

4. Prior pelvic RT

5. Treatment with another investigational drug for prostate cancer

6. Pre-existing conditions or overall health status which disqualifies the patient from curative-intent RT

7. Prior or concurrent invasive pelvic malignancy (except non-melanomatous skin cancer) or lymphomatous or hematogenous malignancy, unless disease free for a minimum of 5 years

8. Patients with distant metastases from prostate cancer

9. Patients with lymph node involvement by prostate cancer

10. Prior prostatectomy, cryotherapy, high-intensity focused ultrasound, pelvic irradiation overlapping with fields needed for prostate cancer treatment, prostate brachytherapy, or previous cytotoxic chemotherapy for prostate cancer

11. Unwilling or unable to provide informed consent

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Radiation:
• SUPR-SABR treatment
SUPR-SABR prescription dose to the PTV_4000 will be 8 Gy per fraction for five fractions. The prescription dose to PTV_3625 will be a minimum of 7.25 Gy per fraction for five fractions. SABR will be delivered 2-3 times a week, every other day. There will be a minimum of 40 hours between fractions and maximum of 128 hours between fractions.

Locations

Country	Name	City	State
United States	Medical University of South Carolina Hollings Cancer Center	Charleston	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of South Carolina

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	12 month Expanded Prostate Cancer Index Composite (EPIC) genitourinary score	EPIC score at 12 months post intervention will be compared with pre-intervention scores. Score scale is 0 to 100 with lower scores indicating more severe symptoms.	12 months
Primary	12 month Expanded Prostate Cancer Index Composite (EPIC) gastrointestinal score	EPIC score at 12 months post intervention will be compared with pre-intervention scores. Score is 0 to 100 with lower scores indicating more severe symptoms.	12 months
Secondary	24 month Expanded Prostate Cancer Index Composite (EPIC) genitourinary score	EPIC score at 24 months post intervention will be compared with pre-intervention scores. Score is 0 to 100 with lower scores indicating more severe symptoms.	24 months
Secondary	24 month Expanded Prostate Cancer Index Composite (EPIC) gastrointestinal score	EPIC score at 24 months post intervention will be compared with pre-intervention scores. Score is 0 to 100 with lower scores indicating more severe symptoms.	24 months
Secondary	Incidence of Common Terminology Criteria for Adverse Events (CTCAE) version 5 grade 3 or higher adverse events from radiation therapy	CTCAE adverse events are on a scale of 0 to 5 with 5 indicating the most severe events.	24 months
Secondary	1 month genitourinary toxicity as assessed by the International Prostate Symptom Score (IPSS)	The IPSS is made up of 7 questions related to voiding symptoms. A score of 0 to 7 indicates mild symptoms, 8 to 19 indicates moderate symptoms and 20 to 35 indicates severe symptoms. IPSS scores at 1 month will be compared with baseline pretreatment IPSS scores.	1 month
Secondary	12 and 24 month erectile function as assessed by the Sexual Health Inventory for Men (SHIM) score.	SHIM score is on a scale of 5-25 with lower scores indicating more severe symptoms of erectile dysfunction.	24 months
Secondary	Biochemical failure rate at 24 months.	Biochemical failure will be reported as a percentage. biochemical failure is defined as prostate specific antigen nadir post treatment + 2 ng/mL.	24 months
Secondary	To correlate changes in Sexual Health Inventory for Men (SHIM) score at 12 and 24 months with radiation dose to the pudendal artery (Gy)	SHIM score is 5 to 25 with lower scores indicating worse erectile function	24 months