PRE-ProstAtectomy MRI-GuidEd Stereotactic Body RadioTherapy for High-Risk Prostate Cancer Trial (PREPARE SBRT) (PREPARE SBRT)

Men with prostate cancer with Gleason Score of 8 or greater or clinical/radiographic evidence of T3 disease will be considered for this trial.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Radiation: 5 Gy x 5 fractions; Radiation: 6 Gy x 5 fractions; Radiation: 6.5 Gy x 5 fractions; Radiation: maximum tolerated dose (6.5 Gy x 5 fractions); Radiation: recommended phase 2 dose (6.5 Gy x 5 fractions)

Detailed Description

Patients with a diagnosis of high risk prostate cancer with a Gleason score of 8 or greater are eligible for this trial. The study will enroll 20 subjects in 3 years. This is a single-arm study including two parts. Part 1 will be a modified dose escalation and de-escalation study to determine maximum tolerated dose (MTD) and the recommended phase II dose (RP2D) based on acute toxicity measures. Part 2 will be a cohort expansion study to further evaluate the safety and tolerability of the RP2D based on toxicities measured at 1 year.

For Part 1, the primary endpoint is to assess if a patient can undergo a radical prostatectomy after SBRT without a post-operative GU and/or GI grade 3 or higher toxicity (according to Clavien-Dindo Classification) at 30 days.

For Part 2, the primary endpoint is to assess GU and/or GI grade 3 or higher toxicity based on CTCAE v5.0 at 1 year.

The previously entered quality-of-life measure was removed to align the record with the primary and secondary endpoints as pre-specified in the IRB-approved protocol.

Exploratory objectives will include analysis of tumor and normal biopsied and resected tissue and serum markers and interpretation of interfraction and intrafraction MRIs.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men aged greater than equal to18 with histologically confirmed primary prostate cancer.
• KPS greater than equal to 70
• Patient with a negative staging bone scan.
• Patient can undergo an MRI.
• Patient with negative staging CT or MRI of pelvis. Suspicious evidence of nodal involvement on staging CT or MRI of pelvis is defined as greater than 1 cm on short axis. Documented negative biopsy of suspicious node required.
• Patient is medically fit to undergo prostatectomy.
• Patient has either Gleason Score greater than equal to 8 on biopsy and/or clinical/radiographic evidence of T3 disease.

Exclusion Criteria:

• Prior history of receiving pelvic radiotherapy.
• Patient is unwilling to undergo prostatectomy.
• Patient with active inflammatory bowel disease defined as currently receiving therapy for IBD.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Part 1 - Arm 5 Gy x 5 fractions; Part 1 uses a modified 3+3 dose escalation/de-escalation design with expansion to define the RP2D in a minimum of 3 to a maximum of 9 patients. DLT is defined as Grade ≥3 GI and/or GU toxicity related to preoperative radiotherapy per Clavien-Dindo within 30 days. Three dose levels are evaluated: 5 Gy, 6 Gy, and 6.5 Gy. At each level, 3 patients are treated over five days. If 0/3 experience DLT, escalate. If 1/3 has DLT, expand to 6. If ≤1/6 have DLT, escalate; if ≥2/6, de-escalate and define the prior dose as MTD. The MTD is expanded to 9 patients. If ≤2/9 have DLT, it is the RP2D; if ≥3/9, further de-escalation occurs. In the arm "Part 1 - Arm 5 Gy x 5 fractions" the participants will receive a dose of 5 Gy for each RT fraction for a total of 5 fractions (total dose 25 Gy).	Radiation: 5 Gy x 5 fractions; In the arm "Part 1 - Arm 5 Gy x 5 fractions" the participants will receive a dose of 5 Gy for each RT fraction for a total of 5 fractions (total dose 25 Gy).
Other: Part 1 - Arm 6 Gy x 5 fractions; Part 1 uses a modified 3+3 dose escalation/de-escalation design with expansion to define the RP2D in a minimum of 3 to a maximum of 9 patients. DLT is defined as Grade ≥3 GI and/or GU toxicity related to preoperative radiotherapy per Clavien-Dindo within 30 days. Three dose levels are evaluated: 5 Gy, 6 Gy, and 6.5 Gy. At each level, 3 patients are treated over five days. If 0/3 experience DLT, escalate. If 1/3 has DLT, expand to 6. If ≤1/6 have DLT, escalate; if ≥2/6, de-escalate and define the prior dose as MTD. The MTD is expanded to 9 patients. If ≤2/9 have DLT, it is the RP2D; if ≥3/9, further de-escalation occurs. In the arm "Part 1 - Arm 6 Gy x 5 fractions" the participants will receive a dose of 6 Gy for each RT fraction for a total of 5 fractions (total dose 30 Gy).	Radiation: 6 Gy x 5 fractions; In the arm "Part 1 - Arm 6 Gy x 5 fractions" the participants will receive a dose of 6 Gy for each RT fraction for a total of 5 fractions (total dose 30 Gy).
Other: Part 1 - Arm 6.5 Gy x 5 fractions; Part 1 uses a modified 3+3 dose escalation/de-escalation design with expansion to define the RP2D in a minimum of 3 to a maximum of 9 patients. DLT is defined as Grade ≥3 GI and/or GU toxicity related to preoperative radiotherapy per Clavien-Dindo within 30 days. Three dose levels are evaluated: 5 Gy, 6 Gy, and 6.5 Gy. At each level, 3 patients are treated over five days. If 0/3 experience DLT, escalate. If 1/3 has DLT, expand to 6. If ≤1/6 have DLT, escalate; if ≥2/6, de-escalate and define the prior dose as MTD. The MTD is expanded to 9 patients. If ≤2/9 have DLT, it is the RP2D; if ≥3/9, further de-escalation occurs. In the arm "Part 1 - Arm 6.5 Gy x 5 fractions" the participants will receive a dose of 6.5 Gy for each RT fraction for a total of 5 fractions (total dose 32.5 Gy).	Radiation: 6.5 Gy x 5 fractions; In the arm "Part 1 - Arm 6.5 Gy x 5 fractions" the participants will receive a dose of 6.5 Gy for each RT fraction for a total of 5 fractions (total dose 32.5 Gy).
Other: Part 1 - ARM MTD expansion cohort; Part 1 uses a modified 3+3 dose escalation/de-escalation design with expansion to define the RP2D in a minimum of 3 to a maximum of 9 patients. DLT is defined as Grade ≥3 GI and/or GU toxicity related to preoperative radiotherapy per Clavien-Dindo within 30 days. Three dose levels are evaluated: 5 Gy, 6 Gy, and 6.5 Gy. At each level, 3 patients are treated over five days. If 0/3 experience DLT, escalate. If 1/3 has DLT, expand to 6. If ≤1/6 have DLT, escalate; if ≥2/6, de-escalate and define the prior dose as MTD. The MTD is expanded to 9 patients. If ≤2/9 have DLT, it is the RP2D; if ≥3/9, further de-escalation occurs. In the arm "Part 1 - MTD Expansion Cohort" participants will receive the dose established as the maximum tolerated dose (MTD) based on the previously tested dose levels.	Radiation: maximum tolerated dose (6.5 Gy x 5 fractions); In the arm "Part 1 - MTD Expansion Cohort" participants will receive the dose established as the maximum tolerated dose (MTD) based on the previously tested dose levels.
Other: Part 2 - Arm RP2D; In part 2 of the study, additional 21 patients will be enrolled to further examine the safety of the R2PD in a total of 30 patients. The primary safety endpoint will be G2+ GI and/or GU AEs related to preoperative radiotherapy according to the CTCAE v5.0 measured at 1 year. Patients will be continuously monitored to ensure the acute G3+ GU and/or GI AEs based on the Clavien-Dindo Classification at 30 days do not exceed 4 of 18 patients, and 6 of 27 patients. In the arm "Part 2 - Arm RP2D" participants will receive the dose established as the recommended phase 2 dose (RP2D) based on the previously tested dose levels.	Radiation: recommended phase 2 dose (6.5 Gy x 5 fractions); In the arm "Part 2 - Arm RP2D" participants will receive the dose established as the recommended phase 2 dose (RP2D) based on the previously tested dose levels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Who Successfully Complete Radical Prostatectomy After SBRT Without a Post-operative DLT of Grade 3 or Higher (Part 1)	Part 1: Successful completion of radical prostatectomy after SBRT without a post-operative dose limiting toxicity (DLT) of grade 3 or higher within 1 month after prostatectomy according to the Clavien-Dindo Classification.	1 month
Number of Gastric-intestinal (GI) and/or Genitor-urinary (GU) Adverse Events Equal or Higher G3 Related to Preoperative Radiotherapy According to the CTCAE v5.0 Measured at 1 Year (Part 2)	Part 2: Successful completion of radical prostatectomy after SBRT without a post-operative DLT of grade 3 or higher within 1 year after prostatectomy.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Toxicity in Patients After Stereotactic Body Radiotherapy (SBRT) and Radical Prostatectomy (RP) Will be Assessed Based on NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (Part 2).	Acute toxicity in patients after stereotactic body radiotherapy (SBRT) and radical prostatectomy (RP) will be assessed based on NCI Common terminology criteria for adverse events (CTCAE) version 5.0.	3 months

Collaborators and Investigators

• Sponsor: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Silvia C. Formenti, M.D., Weill Cornell Medicine - New York Presbyterian Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2018
• Primary Completion (Actual): December 31, 2023
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: August 30, 2018
• First Submitted That Met QC Criteria: September 6, 2018
• First Posted (Actual): September 10, 2018

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 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; Physiological Phenomena; Pharmacological and Toxicological Phenomena; Toxicity Tests; Toxicological Phenomena; Maximum Tolerated Dose
• Other Study ID Numbers: 1712018849

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: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No