Trial Outcomes & Findings for PRE-ProstAtectomy MRI-GuidEd Stereotactic Body RadioTherapy for High-Risk Prostate Cancer Trial (PREPARE SBRT) (NCT NCT03663218)

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). 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).

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). 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).

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). 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).

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. 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.

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. 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.

n=3 Participants

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). 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).

n=3 Participants

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). 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).

n=4 Participants

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). 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).

n=6 Participants

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. 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.

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. 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.

n=16 Participants

Total of all reporting groups

n=3 Participants

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). 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).

n=3 Participants

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). 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).

n=4 Participants

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). 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).

n=6 Participants

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. 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.

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. 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.

n=3 participants at risk

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). 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).

n=3 participants at risk

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). 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).

n=4 participants at risk

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). 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).

n=6 participants at risk

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. 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.

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. 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.