PRE-ProstAtectomy MRI-GuidEd Stereotactic Body RadioTherapy for High-Risk Prostate Cancer Trial (PREPARE SBRT)
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Subjects Who Successfully Complete Radical Prostatectomy After SBRT Without a Post-operative DLT of Grade 3 or Higher (Part 1)
研究概览
简要总结
Men with prostate cancer with Gleason Score of 8 or greater or clinical/radiographic evidence of T3 disease will be considered for this trial.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: maximum tolerated dose (6.5 Gy x 5 fractions) (Radiation)
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).
干预措施: 5 Gy x 5 fractions (Radiation)
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).
干预措施: 6 Gy x 5 fractions (Radiation)
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).
干预措施: 6.5 Gy x 5 fractions (Radiation)
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.
干预措施: recommended phase 2 dose (6.5 Gy x 5 fractions) (Radiation)
结局指标
主要结局
Number of Subjects Who Successfully Complete Radical Prostatectomy After SBRT Without a Post-operative DLT of Grade 3 or Higher (Part 1)
时间窗: 1 month
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.
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)
时间窗: 1 year
Part 2: Successful completion of radical prostatectomy after SBRT without a post-operative DLT of grade 3 or higher within 1 year after prostatectomy.
次要结局
- 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).(3 months)