Adaptive Stereotactic Body Radiation Therapy to the Prostate and Pelvic Nodes With Simultaneous Integrated Boost to the MR-detected Nodule for Patients With High-risk and Unfavorable Intermediate-risk Prostate Cancer

Not Applicable

Active, not recruiting

• Conditions: Prostate Cancer; Cancer of the Prostate
• Interventions: Device: Ethos Varian treatment system; Radiation: Adaptive stereotactic body radiotherapy; Drug: Androgen deprivation therapy

• Registration Number: NCT05628363
• Lead Sponsor: Washington University School of Medicine

Brief Summary

This trial is a prospective clinical trial designed to demonstrate the safety and feasibility of whole-pelvis adaptive prostate stereotactic body radiation therapy (SBRT) with a tumor boost to the magnetic resonance (MR)-detected sites of disease. The hypothesis is that this treatment approach will be safe and feasible with \<15% of patients experiencing an acute CTCAEv5 grade ≥3 genitourinary (GU) or gastrointestinal (GI) adverse event.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-16
• Study First Submitted QC: 2022-11-16
• Study First Posted: 2022-11-28
• Study Start: 2023-01-18
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-30
• Last Update Posted: 2025-08-01
• Primary Completion: 2025-10-25
• Study Completion: 2030-07-25

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 28

Inclusion Criteria

• Pathologically proven adenocarcinoma of the prostate with NCCN high-risk disease or NCCN unfavorable intermediate-risk disease.

• Patients with unfavorable intermediate-risk disease must meet the following criteria:

  • At least one intermediate risk factor (IRF):

    • PSA 10-20 ng/mL
    • cT2b-c (AJCC 8th ed.)
    • Gleason score 7

  • At least one "unfavorable" intermediate-risk identifier:

    • > 1 IRF
    • Gleason score 4+3
    • ≥ 50% of biopsy cores positive

  • NO high-risk features

  • Predicted risk of lymph node involvement ≥ 10% using the Memorial Sloan-Kettering prostate cancer nomogram

• Patients with high-risk disease must meet at least one of the following criteria:

  • cT3a-T3b
  • PSA > 20
  • Gleason score ≥ 8

• 3T MRI scan of the prostate with at least one MR-detectable PIRADS 3 lesion in the prostate/seminal vesicles. PET/CT which is found to display activity n the prostate consistent with prostate cancer may be substituted per investigator discretion.

• Planning to undergo concurrent whole-pelvis SBRT and androgen deprivation therapy (ADT). ADT may be initiated at any time per institutional standard, so long as ADT begins within 60 days of the start of radiotherapy.

• At least 18 years of age.

• ECOG performance status ≤ 1

• Agreement to adhere to Lifestyle Considerations throughout study duration

• Able to complete relevant patient-reported quality-of-life questionnaires in the opinion of the treating physician.

• Able to understand and willing to sign an IRB approved written informed consent document.

Exclusion Criteria

• Definitive radiologic evidence of nodal (cN+) or metastatic (cM1) disease on conventional imaging (bone scan) or prostate cancer-specific PET/CT scan (NaF PET/CT, Axumin PET/CT, fluciclovine, choline, or PSMA PET/CT scan). Patients with lymph nodes ≥ 1 cm on short axis are ineligible unless the lymph node is read as benign by Radiology.
• Prior androgen deprivation therapy. (If the onset of androgen ablation is ≤ 60 days prior to treatment start, the patient is eligible.) Baseline PSA and testosterone must be obtained prior to start of treatment.
• Systemic chemotherapy within 3 years prior to treatment start.
• Prior radical prostatectomy, pelvic lymph node dissection, prostate cryotherapy, or high-intensity focused ultrasound (HIFU) to the prostate.
• Prior pelvic radiotherapy.
• Presence of baseline CTCAE grade ≥ 2 GI or GU toxicity that does not resolve to grade 1 or less with appropriate intervention.
• cT4 disease.
• American Urologic Association (AUA) urinary symptom score ≥ 20
• Prostate gland measuring >90 cc.
• Unable to get prostate fiducial markers placed for image guided radiation treatment. Rectal hydrogel is optional and is left to the discretion of the treating physician.
• Patients with only PIRADS score of 3 lesions and no MR-fusion biopsy pathologic correlation.
• Hip prosthetic.
• Prior malignancy (except for non-melanoma skin cancer) unless disease-free for at least 2 years. Patients are not eligible if they have had a prior pelvic malignancy (e.g. bladder cancer, rectal cancer).
• Prior transurethral resection of the prostate (TURP) within 3 months prior to registration.
• Uncontrolled intercurrent illness precluding RT and/or ADT including, but not limited to, seizures, myocardial infarction in the past 6 months, current severe or unstable angina pectoris, congestive heart failure requiring hospitalization in the past 6 months, uncontrolled active infection, uncontrolled hypertension, or any condition that in the opinion of the investigator would preclude participation in the study.
• History of inflammatory bowel disease, including ulcerative colitis and Crohn's disease.
• Presence of anal fissure or history of bowel or bladder fistula.
• Scleroderma. Patients who are moderately symptomatic from other autoimmune diseases or patients on biologic therapies for autoimmune diseases are also excluded.
• Known history of HIV or chronic hepatitis B or C. Testing to evaluate for the presence of HIV and/or hepatitis B or C is not required in patients who do not carry the diagnosis.
• Poorly visualized bladder and bowel on diagnostic CT or CT simulation (either due to body habitus or artifact).
• Unable to spend 30 minutes lying on the radiation therapy treatment couch due to significant urinary frequency/urgency or other comorbidities.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adaptive stereotactic body radiotherapy (SBRT)	Ethos Varian treatment system	* Treatment consists of adaptive dose-escalated stereotactic body radiotherapy (SBRT) to the pelvic nodes to 25 Gy in 5 once or twice weekly fractions with simultaneous integrated boosts (SIB) to the prostate and proximal seminal vesicles to 36.25 Gy in 5 fractions (full seminal vesicles if involved), to the prostate to 40 Gy in 5 fractions, and to the involved MR-detected nodule(s) to up to 50 Gy in 5 fractions. * Androgen deprivation therapy (ADT) will be administered to study patients according to institutional standard. Unfavorable Intermediate-risk Disease: Patients should receive a minimum of 4 months of ADT. Patients can receive longer duration of ADT at the discretion of the treating physician. High-risk disease: Patients should receive a minimum of 1 year of ADT. Patients can receive up to 2 years of ADT at the discretion of the treating physician.
Adaptive stereotactic body radiotherapy (SBRT)	Adaptive stereotactic body radiotherapy	* Treatment consists of adaptive dose-escalated stereotactic body radiotherapy (SBRT) to the pelvic nodes to 25 Gy in 5 once or twice weekly fractions with simultaneous integrated boosts (SIB) to the prostate and proximal seminal vesicles to 36.25 Gy in 5 fractions (full seminal vesicles if involved), to the prostate to 40 Gy in 5 fractions, and to the involved MR-detected nodule(s) to up to 50 Gy in 5 fractions. * Androgen deprivation therapy (ADT) will be administered to study patients according to institutional standard. Unfavorable Intermediate-risk Disease: Patients should receive a minimum of 4 months of ADT. Patients can receive longer duration of ADT at the discretion of the treating physician. High-risk disease: Patients should receive a minimum of 1 year of ADT. Patients can receive up to 2 years of ADT at the discretion of the treating physician.
Adaptive stereotactic body radiotherapy (SBRT)	Androgen deprivation therapy	* Treatment consists of adaptive dose-escalated stereotactic body radiotherapy (SBRT) to the pelvic nodes to 25 Gy in 5 once or twice weekly fractions with simultaneous integrated boosts (SIB) to the prostate and proximal seminal vesicles to 36.25 Gy in 5 fractions (full seminal vesicles if involved), to the prostate to 40 Gy in 5 fractions, and to the involved MR-detected nodule(s) to up to 50 Gy in 5 fractions. * Androgen deprivation therapy (ADT) will be administered to study patients according to institutional standard. Unfavorable Intermediate-risk Disease: Patients should receive a minimum of 4 months of ADT. Patients can receive longer duration of ADT at the discretion of the treating physician. High-risk disease: Patients should receive a minimum of 1 year of ADT. Patients can receive up to 2 years of ADT at the discretion of the treating physician.

Primary Outcome Measures

Name	Time	Method
Rate of acute grade ≥3 GI and GU adverse events	From start of radiotherapy through 90 days after start of radiotherapy

Secondary Outcome Measures

Name	Time	Method
Changes in patient-reported quality of life as measured by EPIC-26	At screening, end of radiotherapy (week 5), 3 months after start of radiotherapy, and every 3 months until month 24	-The EPIC-26 is used to assess health related quality of life among persons with prostate cancer. It contains 5 domains of urinary incontinence, urinary irritability/obstructive, bowel, sexual, and hormonal. Response options for each EPIC item form a Likert scale, and multi-item scale scores are transformed linearly to a 0-100 scale, with higher scores representing better health related quality of life.
Changes in global function as measured by EQ-5D-5L	At screening, end of radiotherapy (week 5), 3 months after start of radiotherapy, and every 3 months until month 24	-The EQ-5D-5L is a commonly used and reliable questionnaire used to assess patient perception of their current health state. Patients are asked about their levels of difficulty with mobility, self-care, and usual activities, and about their pain/discomfort and anxiety/depression levels on a 5-point scale where the response "I have no problems" = 1 and "I am unable/have extreme" = 5.
Rate of acute grade ≥3 adverse events at least possibly related to radiotherapy	From start of radiotherapy through 90 days after start of radiotherapy
Rate of acute <grade 3 GI and GU adverse events	From start of radiotherapy through 90 days after start of radiotherapy
Rate of late grade ≥3 adverse events at least possibly related to radiotherapy	From day 91 after the start of radiotherapy until completion of follow-up at month 60

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States