Study of PSMA PET/MR Guided Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost (SBRT-SIB) for High-Intermediate and High Risk Prostate Cancer (PSMA SBRT-SIB)

Single-Arm Phase II Study of PSMA PET/MR Guided Stereotactic Body Radiation Therapy With Simultaneous Integrated Boost (SBRT-SIB) for High-Intermediate and High Risk Prostate Cancer

This is a single-arm Phase II clinical trial assessing the clinical efficacy of prostate specific membrane antigen (PSMA) PET/MR guided MR-LINAC based SBRT-SIB with planned accrual of 50 patients.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: PSMA PET/MR - Gallium-68 labeled PSMA-HBED-CC; Radiation: Stereotactic Body Radiation Therapy (SBRT)

Detailed Description

Localized prostate cancer can be treated in 5 sessions using a precise, targeted form of radiation known as stereotactic body radiation therapy (SBRT), with low toxicity. Despite these advances, overall outcomes for aggressive (high risk) prostate cancer remain poor, with 10-year recurrence-free survival of approximately 65% regardless of treatment modality. Recurrences are typically distant and carry poor prognosis, with 5 year survival of 25%. The investigators propose to utilize the latest advances in cancer imaging (PSMA Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MR)) and radiation delivery (MR-guided radiation therapy with real-time adaptive planning), to deliver a personalized radiation treatment that targets the areas of greatest risk of recurrence in the prostate with improved precision, and as a result improve clinical outcomes for individuals with high risk prostate cancer. PSMA PET/MR is a novel imaging modality, not yet widely available, that augments the tissue detail provided by MR. The combination of PSMA PET with MR results in improved delineation of intraprostatic nodules and higher diagnostic accuracy for detection of metastatic disease compared to conventional imaging. PSMA PET/MR imaging data is readily transferable to a MR-based linear accelerator (MR-LINAC), a novel, innovative platform that allows direct visualization of the tumor during treatment, and permits real-time individualized correction for motion with online adaptive radiation planning.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Fabiana Gregucci, M.D.; Phone Number: 646-962-3110; Email: fgr4002@med.cornell.edu
• Study Contact Backup: Name: Dakota Trick; Phone Number: 646-962-3118; Email: dat4015@med.cornell.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065'
      • Recruiting
      • Weill Cornell Medicine
      • Principal Investigator: Silvia Formenti, M.D.
      • Contact: Fabiana Gregucci, M.D.; Phone Number: 646-962-3110; Email: fgr4002@med.cornell.edu
      • Contact: Dakota Trick; Phone Number: 646-962-3118; Email: dat4015@med.cornell.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male aged 21 years or older.
• Ability to provide signed informed consent and willingness to comply with protocol requirements.
• Pathologic confirmation of high-risk adenocarcinoma of the prostate gland as follows: a. Gleason 8-10 or tertiary component 5 disease and/or b. PSA of 20 ng/ml or greater and/or c. Tumor stage of T2c or greater; OR Unfavorable intermediate risk (Gleason 4+3=7, >50% of cores involved, or 2 or more intermediate risk factors which include Gleason 7 disease, PSA 10-20, or T2b disease)
• Participants must agree to use an acceptable form of birth control and utilize condoms for a period of seven days after each PSMA injection, if engaged in sexual activity.
• No evidence of metastatic disease, including pelvic lymph nodes.

Exclusion Criteria:

• Clinical and/or technical factors that would compromise statistical analysis of the PET and/or MR.
• Contraindications to PSMA IV administration
• Contraindications to prostate SBRT (history of transurethral resection of prostate; prostate size greater than 150 cc; AUA score greater than 20; history of prior radiation to the prostate)
• Other unspecified reasons that, in the opinion of investigators, make the subject unsuitable for enrollment
• Patients on or intending to take abiraterone will be excluded

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Single Arm; Patients enrolling on the protocol will undergo prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET)/Magnetic Resonance(MR) prior to start of the radiation treatment planning process. PSMA tracer is administered by IV injection and PET images are acquired. Any patients found to have possible metastatic disease will undergo a standard of care confirmatory biopsy (if feasible) and receive treatment appropriate for their stage. The PSMA PET/MR scan will be performed prior to initiation of androgen deprivation therapy (ADT).

Drug: PSMA PET/MR - Gallium-68 labeled PSMA-HBED-CC; Patients enrolling on the protocol will undergo prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET)/Magnetic Resonance(MR) prior to start of the radiation treatment planning process. PSMA tracer is administered by IV injection and PET images are acquired. Any patients found to have possible metastatic disease will undergo a standard of care confirmatory biopsy (if feasible) and receive treatment appropriate for their stage. The PSMA PET/MR scan will be performed prior to initiation of androgen deprivation therapy (ADT).; Radiation: Stereotactic Body Radiation Therapy (SBRT); Patients will receive standard of care radiation therapy (SBRT)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical efficacy of prostate-specific membrane antigen (PSMA) Positron Emission Tomography (PET)/Magnetic Resonance(MR), MR-Linear Accelerator (LINAC) will be assessed by evaluating recurrence free survival	Evaluate the clinical efficacy of PSMA PET/MR guided, MR-LINAC-based SBRT- SIB in high-intermediate and high risk prostate cancer, as evaluated by the 2-year recurrence-free survival rate	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance of PSMA PET/MR to MR alone at staging prostate cancer	Detection of metastatic disease on each scan will be recorded, with pathologic confirmation obtained. Detection of intraprostatic nodules will be recorded with pathologic confirmation obtained.	Baseline
Performance of PSMA PET/MR to MR alone for identification of dominant intraprostatic nodules during radiation planning	The Dominant Intraprostatic Nodules (DIN) will be defined with radiologist assistance on MR alone, and subsequently PSMA PET/MR. The incidence of alterations in target will be recorded.	Baseline
Compare imaging biomarkers of interest on MR and PSMA PET/MR as predictors of treatment response, versus biopsy of treatment response and PSA		Baseline
Compare imaging biomarkers of interest on MR and PSMA PET/MR as predictors of treatment response, versus biopsy of treatment response and PSA		12 months
Change in Quality of life questionnaires (EPIC-26) will be assessed.	Expanded Prostate Cancer Index Composite (EPIC) short form questionnaire. The Expanded Prostate Cancer Index Composite (EPIC) is a comprehensive instrument designed to evaluate patient function and bother after prostate cancer treatment. Scores range from 0 to 100, lower scores indicate worse outcomes and higher EPIC scores represent better outcomes.	Baseline, 1month, 6months, 12 months, 18 months and 24 months.
Change in The American Urological Association (AUA) symptom score	The American Urological Association (AUA) has created this symptom index for understanding the severity of enlarged prostate symptoms. Scores ranging from 0-7 are considered to be mild symptoms, 8-19 are moderate and 20 - 35 are severe symptoms.	Baseline, 1month, 6months, 12 months, 18 months and 24 months.
Change in Number of Subjects with Adverse events	Adverse events will be collected from patients based on CTCAE version 5.0.	Baseline, 1month, 6months, 12 months and 24 months.
The change in radiation doses received by the surrounding normal structures/PTV for each initial and adapted plan will be analyzed with a signed-rank Wilcoxon test (non-parametric test for paired comparisons).	PTV is the planning target volume	Baseline, 1month
Compare the changes in the Microbiome during SBRT-SIB	Gut microbiome samples will be obtained for 16S RNA analyses	Baseline
Compare the changes in the Microbiome during SBRT-SIB	Gut microbiome samples will be obtained for 16S RNA analyses	approx. 3 weeks
Compare the changes in the Microbiome during SBRT-SIB	Gut microbiome samples will be obtained for 16S RNA analyses	12 months
Compare the immunological changes during SBRT-SIB	serum samples will be obtained for immune correlate analyses	Baseline
Compare the immunological changes during SBRT-SIB	serum samples will be obtained for immune correlate analyses	approx. 3 weeks
Compare the immunological changes during SBRT-SIB	serum samples will be obtained for immune correlate analyses	12 months

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Collaborators: National Cancer Institute (NCI); Telix Pharmaceuticals
• Investigators: Principal Investigator: Silvia Formenti, M.D., Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 8, 2020
• First Submitted That Met QC Criteria: May 21, 2020
• First Posted (Actual): May 26, 2020

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: 19-10020928; R01CA249615 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: Yes