Stereotactic Ablative Radiation Therapy for Prostate Cancer

NCT ID: NCT05668351

Last Updated: 2025-02-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-12
• Study Completion Date: 2028-01-15

Brief 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.

Detailed 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.

Conditions

Prostate Cancer

Keywords

stereotactic body radiation therapy; stereotactic ablative body radiotherapy; SBRT; SABR; pudendal artery

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SUPR-SABR treatment

The prescription dose of this study will be 40 Gy in 5 fractions assigned to PTV\_4000 which permits sparing of the rectum, urethra and pudendal artery. There will be a secondary dose level of 36.25 Gy in 5 fractions. A minimum dose of 36.25 Gy will be given to the entire prostate PTV\_3625. 36.25 Gy in five fractions is currently endorsed as a standard of care for localized prostate cancer by the National Comprehensive Cancer Network guidelines in prostate cancer. Escalating the therapeutic radiation dose above 36.25 Gy provides potential for improved biochemical control of prostate cancer and decrease in relapse free survival.

Group Type: EXPERIMENTAL

SUPR-SABR treatment

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: RADIATION

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Harriet Eldredge-Hindy

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Harriet Eldredge-Hindy, MD

Role: PRINCIPAL_INVESTIGATOR

MUSC Department of Radiation Oncology

Locations

Medical University of South Carolina Hollings Cancer Center

Charleston, South Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Alan Brisendine

Role: CONTACT

Phone: 843-792-6382

Email: brisend@musc.edu

Jasmin Brooks

Role: CONTACT

Email: brooksjm@musc.edu

Facility Contacts

Harriet Eldredge-Hindy, MD

Role: primary

Other Identifiers

SUPR-SABR 103629

Identifier Type: -

Identifier Source: org_study_id