PRE-ProstAtectomy MRI-GuidEd Stereotactic Body RadioTherapy for High-Risk Prostate Cancer Trial (PREPARE SBRT)
Phase: NA
Conditions: Prostate Cancer
Sponsor: Weill Medical College of Cornell University

 
 
 
COVER PAGE 
 
Official Title: PRE-ProstAtectomy MRI-GuidEd Stereotactic Body RadioTherapy for High-Risk 
Prostate Cancer Trial (PREPARE SBRT) 
IRB Protocol #: 19-07020533 
NCT03663218 
Document date: 09OCT2024 
 

Protocol # 1712018849 
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TITLE: 
PRE-ProstAtectomy MRI-GuidEd Stereotactic Body RadioTherapy for High-Risk Prostate Cancer 
Trial (PREPARE SBRT) 
 
IRB Protocol #: 1712018849 
Version number: 7.0 
Version Date: 09OCT2024 
 
Principal Investigators: 
Silvia Formenti, MD 
 
 
 
 
 
 
Christopher Barbieri, MD PhD 
 
 
 
 
Co-Investigators: 
Sandra Demaria, MD 
 
 
 
 
 
Olivier Elemento, PhD 
 
 
 
 
 
 
Bishoy M.Faltas, MD 
 
 
 
 
 
Jim Hu, MD MPH 
 

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Josephine Kang, MD PhD 
 
 
 
 
 
Francesca Khani, MD 
 
 
 
 
 
Daniel Margolis, MD 
 
 
 
 
Ana M. Molina, MD 
 
 
 
 
 
Juan Miguel Mosquera, MD MSc 
 
 
 
 
David Nanus, MD 
 
 
 
 
Brian D. Robinson, MD 
 
 
 

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Douglas S. Scherr, MD 
 
 
 
 
Peter Schlegel, MD 
 
 
 
 
 
Scott Tagawa, MD MS 
 
 
 
 
Statisticians: 
Study Contact, Radiation Oncology: 
Karla Ballman, PhD 
Fabiana Gregucci, MD 
 
 
 
 
 
 
 
  
 
 
Xi Kathy Zhou 
 
 
 
 
 
 
Responsible Study/Data Manager- Radiation Oncology: 
Dakota Trick 
 
 
 
 
 
  
Maahi Patel 
 
 
 

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For Protocol enrollments and Study related matters, please email our list serv: 
rocto@med.cornell.edu 
  
 
 
Responsible Study contact-Urology: 
Thomas Flynn 
 
 
 
 
 
 
 
 
Responsible Study contact-Urology: 
Miko Yu 
 
 
 
 
 
 
Participating Sites: Weill Cornell Medicine – NewYork-Presbyterian Hospital 
 

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Confidentiality Statement 
This document is confidential and is to be distributed for review only to investigators, potential 
investigators, consultants, study staff, and applicable independent ethics committees or 
institutional review boards. The contents of this document shall not be disclosed to others 
without written authorization from WCM. 

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List of Abbreviations 
All abbreviations used throughout the protocol must be defined. 
 
 
AE 
Adverse Event 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
CTSC 
Clinical Translational Science Center 
DSMB 
Data Safety Monitoring Board 
DSMP 
Data Safety Monitoring Plan 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HRBFA 
Human Research Billing Analysis Form 
HUD 
Humanitarian Use Device 
ICF 
Informed Consent Form 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
PHI 
Protected Health Information 
PI 
Principal Investigator 
REDCap 
Research Electronic Data Capture 
RP 
SAE 
SBRT 
SUSAR 
Radical Prostatectomy 
Serious Adverse Event 
Stereotactic Body Radiotherapy 
Suspected Unexpected Serious Adverse Reaction 
UAP 
Unanticipated Problem 
WCM 
Weill Cornell Medicine 

7 
 
 
Protocol Summary 
 
Full Title: 
 PRE-ProstAtectomy MRI-GuidEd Stereotactic Body RadioTherapy 
for High-Risk Prostate Cancer Trial 
Short Title: 
PREPARE SBRT 
Clinical Phase: 
I 
Principal Investigators: 
Himanshu Nagar and Christopher Barbieri 
Sample Size: 
N = 20-40 (3 patients per dose escalation arm with 7 additional 
patients in maximum tolerated dose arm) 
Accrual Ceiling: 
This study will enroll up to 45 subjects. 
Study Population: 
Men with prostate cancer with Gleason Score of 8 or greater or 
clinical/radiographic evidence of T3 disease 
Accrual Period: 
3 years 
Study Design: 
Single arm, feasibility and safety dose escalation study 
Study Duration: 
Patients will remain on study for 5 years. 
Study Agent/ 
Intervention Description: 
Stereotactic Body Radiotherapy (SBRT) 
Primary Objective: 
The primary outcome is that a patient can undergo a radical 
prostatectomy after SBRT without a post-operative dose limiting 
toxicity (DLT) within 30 days after prostatectomy. DLT will be 
considered as Grade 3 or higher adverse events according to the 
Clavien-Dindo Classification 
Secondary Objectives: 
Secondary objectives include assessment of acute toxicity and 
quality of life scores. 
Exploratory Objectives: 
Exploratory objectives will include analysis of tumor and normal 
biopsied and resected tissue and serum markers and interpretation 
of interfraction and intrafraction MRIs. 
Endpoints: 
The primary endpoint is the ability of a patient to undergo a radical 
prostatectomy without a post-operative Grade 3 or higher adverse 
events within 30 days according to the Clavien-Dindo Classification 

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Document History 
 
Document Name 
Version number 
Version Date 
Amendment 7 
7.0 
09OCT2024 
Amendment 6 
6.0 
10SEP2020 
Amendment 5 
5.0 
26JUN2020 
Amendment 4 
4.1 
18MAR2020 
Amendment 3 
4.0 
10.03.2019 
Amendment 2 
3.0 
06.18.2019 
Amendment 1 
2.0 
10.25.2018 
Initial Protocol 
1.0 
04.24.2018 
Summary of changes: Protocol 09OCT2024 version 7.0 
 
1. Removing Dr. Himanshu Nagar as PI from the protocol, as he has left WCM. 
2. Updating Dr. Formenti's role to be the new PI for the protocol. 
3. Removing Pragya Yadav, Ariel Marciscano, Sharanya Chandrasekhar and Jessica Richman, 
as they have left WCM. 
4. Adding Fabiana Gregucci as Study Contact. 
5. Adding Dakota Trick and Maahi Patel as Responsible Study/Data Manager. 
6. Removing personnel will not affect the integrity of the research. 
Summary of changes: Protocol 10SEP2020 version 6.0 
 
1. Removing Stool sample collection from the protocol. 
2. Updating schema to reflect changes in the study design. 
 
Summary of changes: Protocol 26JUN2020 version 5.0 
 
1. Reducing the dose escalation to include only 3 doses, 5 Gy, 6Gy and 6.5 Gy. 
2. Removing Viji Nagaraj from the study as she is no longer with our department. 
 
 
Summary of changes: Protocol 18MAR2020 version 4.1 
 
1.  Adding Dr. Ariel Marciscano as a Co-investigator on the study. 

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Summary of changes: Protocol 10.03.2019 version 4.0 
1.  
Change study title to PREPARE SBRT: PRE-ProstAtectomy MRI-GuidEd 
Stereotactic Body RadioTherapy for High-Risk Prostate Cancer Trial 
2.  
Modify primary objective and primary end point-- The primary outcome is that a 
patient can undergo a radical prostatectomy after SBRT without a post-operative Dose 
limiting toxicity (DLT). DLT will be defined as Grade 3 or higher adverse events within 30 
days of prostatectomy according to the Clavien-Dindo Classification. 
3.  
In Secondary end points: added International Prostate Symptom Score (IPSS) 
instead of EQ5D. 

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4. 
Revised stats section 8 and stopping rule section 10.2 
5. 
Removed from Exclusion criteria: Prior chemotherapy and ADT 
6. 
Remove pre-surgery research samples from the Table 1 Study procedures 
7.  
Updated- serum to PBMCs in Section 6 to make it consistent with the initial e IRB 
application 
8. 
Added Xi Cathy Zhou as a statistician 
9. 
Remove Michael Smith as a co-investigator. 
 
Summary of changes: Protocol 06.18.2019 version 3.0 
 
1. Removing SPACEOARTM from the protocol as Augmenix is no longer the sponsor of the study. 
2. Adding Viji Nagaraj as an additional data manager for the study 
3. Revising phone numbers for Sharanya and Pragya 
4. Revising study calendar section 5.1. Removing SPACEOARTM from the calendar and indicating that 
certain procedures are required only at the first follow up visit. 
 
 
Summary of changes: Protocol 10/25/2018 version 2.0 
 
1. Revised the time between radiation therapy and surgery from 3-6 weeks to less than 4 weeks. 
2. Removed pre-surgery Radiation Oncology follow up visit 
3. Adding Miko Yu and Thomas Flynn as study coordinators 
 
Informed consent version date 10/25/2018. 
 
1. ICF has been updated to be consistent with the protocol. 

 
SCHEMA 
 
 
 
 
 
 
10 

11 
 
 
Table of Contents 
 
SCHEMA .......................................................................................... ERROR! BOOKMARK NOT DEFINED. 
1 
STUDY OBJECTIVES ...................................................................................................................... 13 
1.1 
Primary Objectives ....................................................................................................................... 13 
1.2 
Secondary Objectives .................................................................................................................. 13 
1.3 
Exploratory Objectives ................................................................................................................ 13 
2 
BACKGROUND .............................................................................................................................. 13 
2.1 
Disease ......................................................................................................................................... 13 
2.2 
Rationale ...................................................................................................................................... 14 
2.3 
Risk/Benefit Assessment ............................................................................................................. 14 
3 
SUBJECT SELECTION ..................................................................................................................... 15 
3.1 
Study Population.......................................................................................................................... 15 
3.2 
Inclusion Criteria .......................................................................................................................... 15 
3.3 
Exclusion Criteria ......................................................................................................................... 15 
4 
REGISTRATION PROCEDURES ...................................................................................................... 16 
4.1 
Patient Registration ..................................................................................................................... 16 
5 
STUDY CALENDAR ........................................................................................................................ 17 
5.1 
Table 1. Schedule of trial events ................................................................................................. 17 
5.2 
Screening Visit ............................................................................................................................. 17 
5.3 
Imaging Studies ............................................................................................................................ 17 
5.4 
Radiation Treatment Planning .................................................................................................... 18 
5.5 
Trial Procedures ........................................................................................................................... 19 
5.6 
General Concomitant Medication and Supportive Care Guidelines ......................................... 19 
5.7 
Duration of Therapy and Criteria for Removal from Study ........................................................ 19 

12 
 
 
5.8 
Duration of Follow Up ................................................................................................................. 20 
6 
CORRELATIVE/SPECIAL STUDIES ................................................................................................. 20 
7 
DATA REPORTING / REGULATORY CONSIDERATIONS ................................................................ 20 
7.1 
Data Collection ............................................................................................................................. 20 
7.2 
REDCap ......................................................................................................................................... 20 
7.3 
Data Management ....................................................................................................................... 21 
7.4 
Regulatory Considerations .......................................................................................................... 21 
8 
STATISTICAL CONSIDERATIONS ................................................................................................... 21 
8.1 
Study Design/Endpoints .............................................................................................................. 21 
8.2 
Sample Size/Accrual Rate ............................................................................................................ 22 
8.3 
Stratification Factors ................................................................................................................... 23 
8.4 
Analysis of Endpoints .................................................................................................................... 23 
8.5 
Analysis of Primary Endpoints .................................................................................................... 23 
8.6 
Analysis of Secondary Endpoints ................................................................................................ 23 
8.7 
Interim Analysis ........................................................................................................................... 23 
9 
ADVERSE EVENT REPORTING REQUIREMENTS ........................................................................... 23 
9.1 
Assessing and Recording Adverse events ................................................................................... 24 
9.2 
Definition of SAE .......................................................................................................................... 25 
10 
DATA AND SAFETY MONITORING PLAN (DSMP) .................................................................... 25 
10.1 
DSMB safety Review .................................................................................................................... 26 
10.2 
Stopping Rules ............................................................................................................................. 26 
11 
REFERENCES ............................................................................................................................. 27 

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1 
Study Objectives 
 
1.1 
Primary Objectives 
 
Assess the feasibility of stereotactic body radiotherapy (SBRT) before radical 
prostatectomy (RP) in patients with high risk prostate cancer. The primary outcome 
is that a patient can undergo a radical prostatectomy after SBRT without a post- 
operative dose limiting toxicity (DLT). DLT will be defined as Grade 3 or higher 
adverse events within 30 days after prostatectomy according to the Clavien-Dindo 
Classification. 
 
1.2 
Secondary Objectives 
 
Assess the acute toxicity and quality of life scores in subjects after SBRT and RP. 
Assess negative margin rate and neurovascular bundle preservation rate. 
 
1.3 
Exploratory Objectives 
 
Analyze tumor and normal biopsied and resected tissue and serum markers. 
Interpret interfraction and intrafraction MRI of prostate and seminal vesicles. 
 
2 
Background 
 
2.1 
Disease 
 
Prostate cancer is the most common non-cutaneous cancer in men and the second leading 
cause of cancer death in men 1. It is predicted that the number of cases will almost double by 
2030 (GLOBOCAN 2012). The standard of care for patients with high-risk prostate include 
radiotherapy with androgen deprivation therapy (ADT) or prostatectomy which may be 
followed by adjuvant therapy 2. Radical prostatectomy is the most common treatment for 
prostate cancer according to the National Cancer Institute’s Pattern of Care study from 14 
regional cancer registries with the proportion of men undergoing prostatectomy was 70% for 
age <60 years, 51% for 60-64 years, and 39% for 65-75 years 3. An increasing number of 
patients with high-risk prostate cancer are undergoing primary radical prostatectomy with a 
20% increase from 2004 to 2012 4. 
High-risk features for recurrence include extra-capsular extension and/or seminal vesicle 
invasion (pT3 disease) and positive surgical margins, which occur in an estimated 20% and 16% 
of patients, respectively 5. Post-prostatectomy radiotherapy to the prostate bed for pT3 
disease or positive surgical margins has been shown to reduce the risk of recurrence in three 

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randomized trials: Southwest Oncology Group, European Organization for Research and 
Treatment of Cancer and Auckland Radiation Oncology 6-8. As such, adjuvant radiotherapy after 
prostatectomy is the standard for care for patients with pT3 disease, positive margins or 
Gleason Grade 8-10 2. 
 
 
2.2 
Rationale 
 
Patients at high risk of recurrence are recommended to undergo post-operative radiotherapy 
as a surrogate to eradicate subclinical disease. The clinical target volume (CTV) is the prostate 
bed which is difficult to delineate once the prostate has been surgically removed and can be 
overestimated by the utilizing location of surgical clips 9. As such, controversy exists in the field 
as to the optimal target volume. National and international guidelines suggest including a 
significant portion of the posterior and inferior aspects of the bladder, and anterior aspect of 
the rectum, exposing a significant amount of normal tissue to high dose radiation 10-12. 
Additionally, post-operative radiotherapy is delivered in 37-39 fractions over the course of 7 
weeks, representing a high burden of therapy, which may be related to lower utilization of 
post-operative radiotherapy 13. 
Modern radiotherapy for untreated prostate cancer has been afforded many advantages 
including improved target delineation with multiparametric MRI and image-guided 
radiotherapy allowing for larger dose delivery in fewer fractions and tighter margins with 
stereotactic body radiotherapy (SBRT) 14. Moreover, newer technologies with MRI based image 
guided radiotherapy with the ViewRay and MRIdian linear accelerator now available at 
NewYork-Presbyterian/Weill Cornell Medicine will allow for significantly improved daily 
adaptive target delineation. 
In patients that are likely to need radiotherapy after RP, the potential advantages of SBRT 
delivered over 5 fractions prior to surgery (preoperative) are: 1) reduced radiation dose to 
normal tissues, 2) increased convenience to patients because of fewer treatment days, 3) 
reduced costs to patients because of reduced travel expenses and copays, 4) improved 
resource utilization for physicians because of the fewer number of treatments per patient and 
overall and consequently 5) reduced cost to society. In prostate cancer specifically, SBRT has 
the added potential of not increasing toxicity while delivering a higher biological dose and 
therefore increased efficacy 16. 
 
2.3 
Risk/Benefit Assessment 

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Two prior phase I trials have explored preoperative radiotherapy prior to prostatectomy for 
patients with high risk prostate cancer. A trial at Duke University treated the patients’ prostate 
and seminal vesicles in a dose escalation fashion in 1.8 Gy daily fractions to total doses of 39.6 
Gy, 45 Gy, 50.4 Gy and 54 Gy. Acute GU and GI toxicities were limited to Grade 1 and no 
observed intraoperative complications occurred. Late urinary toxicity was within the range 
expected for adjuvant radiotherapy 17. A trial at Princess Margaret Hospital utilized a 
preoperative dose of 25 Gy delivered in 5 fractions without image guidance. Similar to the trial 
at Duke University, there were no observed intraoperative complications and urinary toxicity 
was within the range expected for adjuvant radiotherapy 18. The current trial has the 
potential benefit of limiting radiation dose received by normal tissues that would be exposed 
in the postoperative setting, namely the bladder and rectum, with advanced image guided and 
dose delivery techniques. Additionally, as the prior phase I preoperative study using a 
hypofractionated dose of 25 Gy in 5 fractions did not demonstrate significantly different 
toxicities or any observed intraoperative complications, this study will begin at that dose level 
of 5 Gy x 5. 
 
 
3 
Subject Selection 
 
3.1 
Study Population 
 
Subjects with a diagnosis of high-risk prostate cancer who meet the inclusion 
and exclusion criteria will be eligible for participation in this study. 
 
3.2 
Inclusion Criteria 
 
1. Men aged  18 with histologically confirmed primary prostate cancer. 
2. KPS  70 
3. Patient with a negative staging bone scan. 
4. Patient can undergo an MRI. 
5. 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. 
6. Patient is medically fit to undergo prostatectomy. 
7. Patient has either Gleason Score  8 on biopsy and/or clinical/radiographic 
evidence of T3 disease. 
 
3.3 
Exclusion Criteria 

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1. Prior history of receiving pelvic radiotherapy. 
2. Patient is unwilling to undergo prostatectomy. 
3. Patient with active inflammatory bowel disease defined as currently 
receiving therapy for IBD. 
4 
Registration Procedures 
 
4.1 
Patient Registration 
 
Once patient signs consent, please notify via email to rocto@med.cornell.edu. ROCTO will 
begin registration process as soon as the signed consent and the eligibility documents are 
obtained either as hard or soft copies. 
Patients will be centrally registered in onCORE by ROCTO. To register a patient, upload the 
following documents to onCORE: 
• 
Signed Informed consent 
• 
Email the completed eligibility document to CancerCTRegistrar. 
Registration must be completed within 24 hours of the signing of informed consent. 

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5 
Study Calendar 
 
5.1 
Table 1. Schedule of trial events 
 
Screening 
Before 
Radiation 
Day 1 – Day 5 
Radiation therapy 
Tumor assessment 
(pre-surgery) 
Surgery 
(less than 4 
weeks post RT) 
Follow up 1month 
post-surgery and 
q3months for 5 
years 
Radiotherapy 
X 
X 
X 
X 
X 
Surgery 
X 
EPIC SCORE 
X 
X 
X* 
IPSS 
X 
X 
X* 
Informed consent 
X 
Demographics/Medical history 
X 
Physical exam 
X 
X 
X 
X 
PSA serum 
X 
X 
X* 
CT or MRI pelvis (with and 
without contrast) 
X 
X 
Adverse Events 
X 
X 
X 
X 
Immune monitoring samples 
X 
X 
X* 
* - These procedures are required per protocol at the 1st follow up visit (post-surgery) only. 
5.2 
Screening Visit 
• 
Informed Consent 
• 
MRI pelvis 
• 
Medical History, demographics and any baseline adverse events 
• 
Routine Physical exam 
• 
Serum PSA 
5.3 
Imaging Studies 
Patients enrolling on the protocol will be treated as follows. Patients will be instructed to 
undergo a Fleet enema prior to planning CT/MRI and prior to each SBRT treatment. 
Treatment planning CT/MRI will be performed with vac loc immobilization. Patients will be 
advised to drink 1-2 cups of water 1 hour prior to the CT/MRI simulation to allow for a 
comfortably full bladder, if tolerated. A rectal catheter will be utilized to dispel any excess 

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bowel gas, if necessary. A urethral catheter to delineate the urethra at time of simulation can 
be considered if it is difficult to visualize the urethra on initial MRI. 
 
5.4 
Radiation Treatment Planning 
 
After consent and eligibility verification, patients will be undergo CT/MRI simulation/radiation 
therapy planning. This is a dose escalation study and the trial accrues 3 patients at each dose 
level. The dose levels that are being tested are 5 Gy x 5 fractions, 6 Gy x 5 fractions and 6.5 Gy 
x 5 fractions. 
Three (3) patients will initially receive 5 Gy for 5 fractions. If patients tolerate the dose and 
undergo surgery without a post-operative Grade 3 or higher DLT 30 days, another set of 3 
patients are selected for the next dose level. If the patients are to develop a post-operative 
Grade 3 or higher DLT, the trial will accrue additional 6 patients to the previous dose level. 
Contours 
The treatment planning CT will be fused to the T2 sequence of the MRI. The prostate + seminal 
vesicles (SV) will be contoured as the clinical target volume (CTV). The PTV expansion for the 
CTV will be 3-5 mm depending on physician discretion. 
The rectum will be drawn from the bottom of the ischial tuberosities to the sigmoid flexure. 
The urethra will be delineated on MRI from the prostatic apex, to entry of urethra into the 
penile bulb, using a 5 mm brush. The physician will have the option of placing a urethral 
catheter at time of sim as per standard care. 
The bladder, femoral heads, penile bulb will also be contoured as normal structures. 
 
Dose/Treatment Planning Parameters 
The CTV (prostate + SV) will be treated to the prescribed dose (5, 6, or 6.5) Gy 
in 5 fractions. 
PTV = CTV + 3-5 mm (treating physician’s discretion) 
VPrescription Dose (5, 6, or 6.5) Gy (volume of the PTV receiving Prescription 
Dose 
(5, 6, or 6.5) Gy should be ≥ 95% 
 
 
Critical organ limits: 

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1. Rectum: Maximum dose to 1 cc 38.5 Gy, Max dose to 3 cc 34.4 Gy, D53% 24 
Gy, 
 
Max point dose 40 Gy 
2. Bladder: Maximum dose to 1 cc 38.5 Gy, Max point dose 40 Gy 
3. Penile Bulb: No more than 105% of prescription dose; D3cc 25 Gy. This is a 
soft 
constraint. 
4. Femoral heads: Maximum point dose 30 Gy 
5. Small bowel: Maximum point dose 25 Gy 
6. Urethra: Max dose 38.78 Gy 
 
5.5 
Trial Procedures 
 
The Study Procedures Section 5.1 summarizes the trial procedures to be performed at each 
visit. It may be necessary to perform these procedures at unscheduled time points if deemed 
clinically necessary by the investigator. 
5.6 
General Concomitant Medication and Supportive Care Guidelines 
 
a. Urinary: A proportion of patients undergoing prostate SBRT can expect increase in urinary 
frequency or urgency. If this becomes bothersome to the patient, medication to alleviate 
symptoms can be prescribed at the discretion of the treating radiation oncologist and 
documented in patient chart. 
b. Bowel: Bowel symptoms during time of prostate SBRT are rare. If patients develop rectal 
urgency, tenesmus or diarrhea, medication to alleviate symptoms can be prescribed at the 
discretion of the treating radiation oncologist and documented in patient chart. 
 
5.7 
Duration of Therapy and Criteria for Removal from Study 
Radiotherapy will be delivered in a total of 5 fractions. Treatments extending over a weekend 
period are allowed. 
In the absence of treatment delays due to adverse event(s), treatment may continue or until 
one of the following criteria applies: 
o Patients unable to tolerate radiation therapy 
o Intercurrent illness that prevents further administration of treatment, 

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o Unacceptable adverse event(s), 
o Patient decides to withdraw from the study, or 
o General or specific changes in the patient’s condition render the patient unacceptable 
for further treatment in the judgment of the investigator. 
 
5.8 
Duration of Follow Up 
Patients will be followed up 30 days post-surgery. There will be a follow up every 3 months for 
5 years post-surgery or until death, whichever occurs first. Patients removed from study for 
unacceptable adverse events will be followed until resolution or stabilization of the adverse 
event. 
6 
Correlative/Special Studies 
Paraffin-embedded tissue block, PBMCs, plasma will be collected for future translational 
research analyses for predictors of toxicity and response following radiotherapy. Note: Testing 
of banked specimens will not occur until an amendment to this treatment protocol is reviewed 
and approved in accordance with IRB policies. 
7 
Data Reporting / Regulatory Considerations 
 
7.1 
Data Collection 
 
The data collection plan for this study is to utilize REDCap to capture all treatment, toxicity, 
efficacy, and adverse event data for all enrolled patients. 
 
7.2 
REDCap 
 
REDCap (Research Electronic Data Capture) is a free data management software system that is 
fully supported by the Weill-Cornell Medical Center CTSC. It is a tool for the creation of 
customized, secure data management systems that include Web-based data-entry forms, 
reporting tools, and a full array of security features including user and group based privileges, 
authentication using institution LDAP system, with a full audit trail of data manipulation and 
export procedures. REDCap is maintained on CTSC-owned servers that are backed up nightly 
and support encrypted (SSL-based) connections. Nationally, the software is developed, 
enhanced and supported through a multi-institutional consortium led by the Vanderbilt 
University CTSA. 

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7.3 
Data Management 
 
All patient data will be entered and maintained in REDCap. These data include clinical data and 
all patient safety data. The REDCap provides audit trails that track creation and modification of 
records that include user ID and timestamp. Once entered, the data is subjected to validation 
procedures that are executed either immediately or upon saving the eCRF page or during the 
batch validation process. Validation failures that are identified before the page is saved can be 
corrected immediately. Validation failures during saving of the eCRF page and during batch 
validation processes will generate a discrepancy. Depending on the database account 
privileges, the data managers may be able to correct a discrepancy or if not, route it to the 
project data manager at WCMC who can take appropriate action to correct the problem. Once 
the discrepancy is closed, by marking “resolved” or “irresolvable”, the data is marked clean 
and an audit trail is generated by the system. 
All key end points will be source verified by a second person at each site and errors will be 
corrected. Once the data is verified and all discrepancies are closed, the data can be 
locked/frozen. Locking and freezing can be done at different granular levels and will follow 
institutional SOPs and any specific requirements for the project. 
Security measures that will be taken in order to protect patient data will include firewall 
technology and database level security which will be achieved by assigning roles and privileges 
to different levels of users and by requiring that the users authenticate themselves using user 
id and password. Additional security for data transfer between remote clients and servers will 
be achieved by using digital certificates/SSL. All data will be backed-up to tape periodically 
according to the Institutional SOPs. All data will be stored for at least 5 years following the 
termination of this study. 
 
7.4 
Regulatory Considerations 
All protocol amendments and consent form modifications will be made by the Principal 
Investigator. 
8 
Statistical Considerations 
The primary endpoint for this trial will be successful completion of radical prostatectomy after 
SBRT without a post-operative DLT of grade 3 or higher within 30 days after prostatectomy. 
 
 
8.1 
Study Design/Endpoints 
 
This is a single-arm study including two parts. Part 1 will be a modified dose 

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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. 
In part 1 of the study, a modified dose escalation and de-escalation design with an 
expansion of 3 or 6 patients to allow the recommended phase II dose (RP2D) be 
examined in a total of 9 patients will be used. The dose limiting toxicity (DLT) is 
defined as Grade 3 or higher (G3+) gastrointestinal (GI) and/or urinary (GU) AEs 
related to preoperative radiotherapy according to the Clavien-Dindo Classification at 
30 days. Three radiation dose levels, 5 Gy, 6 Gy and 6.5Gy are considered. A 3+3 dose 
escalation plan will be used. At the start of each dose level k (k=1, 2, or 3), 3 patients 
will be enrolled and treated for five days. If none of the 3 patients develop the DLT, 
the testing dose will escalate to the next level, k+1. If 1 of the 3 patients develops 
the DLT, the current dose will be tested in an additional 3 patients. If no additional 
patients develop the DLT, the dose will escalate. If 1 of the additional 3 patients 
develops DLT, i.e. a total of 2 of 6 patients with DLT, the previous dose will be 
deemed the maximum tolerated dose (MTD) and tested in a total of 9 patients. If <=2 
among the 9 patients experience the DLT, this dose will be considered as the RP2D. If 
>=2 of 3 patients or >=2 of 6 patients develop DLT, the study will stop without MTD if 
k=1 or consider dose level k-1 to be the MTD and tested in an additional 3 or 6 
patients so that a total of 9 patients are evaluated. If >=3 of 9 patients experience 
the DLT, the de-escalation will continue. This design ensures that the DLT rate to be 
<=2/9 for the 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. 
 
8.2 
Sample Size/Accrual Rate 
 
The sample size for part 1 portion of the study will vary depending on the number of patients 
that develop the DLT. If no DLTs are seen, we will recruit 3+3+3+6=15= patients at 5, 6, and 6.5 
Gy, respectively. Following the schema above, the maximum number recruited would be 27, 
which would only occur if 0 of 3 or 1 of 6 patients develop the DLT in dose escalation phase but 
>2 of 6 or >1 of 3 patients in the expansion cohort develop the DLT, triggering an expanded 
cohort at a lower dose. 

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Sample size for part 2 portion of the study will be 30 including the 9 patients from part 1. 
Having a total of 30 patients in the expansion cohort will allow us to estimate the 1-year G2+ 
toxicity rate based on CTCAE v5.0 within a 95% CI width of 0.37 and help with the decision 
making at the end of the trial. For example, an observation of >=8 of the 30 patients having 
G2+ toxicity at 1-year based on CTCAE v5.0 would suggest that the probability of the toxicity 
rate being > 0.20 is greater than 80%, which will allow us to make an informative decision on 
whether the R2PD is worth to be examined at a larger trial. 
8.3 
Stratification Factors 
 
No stratification factors are planned for the primary endpoint. 
8.4 
Analysis of Endpoints 
 
8.5 
Analysis of Primary Endpoints 
 
Primary endpoints for this study are G3+ GU and/or GI toxicities at 30 days based on Clavien- 
Dindo Classification (Part 1) and G2+ GU and GI toxicities at 1 year based on CTCAE v5.0 (Part 
2). Adverse events based on the two classification systems will be recorded. Descriptive 
statistics including the number, proportion of patients experience AEs, and 95% confidence 
interval of the proportion estimate calculated using the Clopper-Pearson method will be 
summarized. The analysis set will include patients who receive any dose of the preoperative 
radiation therapy. 
 
8.6 
Analysis of Secondary Endpoints 
 
Assessment and analysis of secondary endpoints including toxicity and quality of life scores 
will be descriptive. 
8.7 
Interim Analysis 
 
This study will have interim analyses after every dose in the sense that if any unacceptable 
dose limiting toxicities are seen, future patients will be recruited at a lower dose. 
9 
Adverse Event Reporting Requirements 
Adverse events (AEs) will be recorded REDCAP for the duration of the trial, regardless of 
whether or not the event(s) are considered related to the trial. All AEs considered related to 
trial medication will be followed until resolution even if this occurs post-trial. 
Adverse events will be recorded for the duration of a patient’s participation in the trial. All 
adverse events (except grade 1 and 2 laboratory abnormalities unless a dose treatment 

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modification, delay or therapeutic intervention is required), regardless of causal relationship, 
are to be recorded in the case report form and source documentation. Pre-existing conditions 
at baseline will be recorded. If a pre-existing condition does not change, it does not have to be 
reported on subsequent cycles. 
The investigator must determine the toxicity of adverse events according to the CTCAE version 
5.0 and their causal relationship. 
9.1 
Assessing and Recording Adverse events 
 
An adverse event is defined as any untoward medical occurrence in a patient or clinical 
investigation participant administered a pharmaceutical product and which does not 
necessarily have to have a causal relationship with this treatment. An adverse event can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, 
for example), symptom, or disease temporally associated with the use of a medicinal product 
or protocol-specified procedure, whether or not considered related to the medicinal product 
or protocol-specified procedure. 
CTCAE term (AE description) and grade: The descriptions and grading scales found in the 
revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be 
utilized for AE reporting. A copy of the CTCAE version 5.0 can be downloaded from the CTEP 
web site (http://ctep.cancer.gov). 
 
Attribution of the AE: 
- Definite – The AE is clearly related to the study treatment. 
- Probable – The AE is likely related to the study treatment. 
- Possible – The AE may be related to the study treatment. 
- Unlikely – The AE is doubtfully related to the study treatment. 
- Unrelated – The AE is clearly NOT related to the study 
treatment. 
 
9.1.1 
Evaluating Adverse Events 
 
An investigator who is a qualified physician will evaluate all adverse events according to the 
NCI Common Terminology for Adverse Events (CTCAE), version 5.0. Any adverse event which 
changes CTCAE grade over the course of a given episode will have each change of grade 
recorded on the adverse event case report forms/worksheets. All adverse events regardless of 
CTCAE grade must also be evaluated for seriousness. 
9.1.2 
Recording of Adverse Events 

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All adverse events will be recorded on a patient specific AE log. The AE log will be maintained 
by the research staff and kept in the patient’s research chart. The AEs are documented in 
REDCAP database. 
 
9.1.3 
Reporting of AE to WCM IRB 
 
All AEs occurring on this study will be reported to the IRB according to the IRB policy, which 
can be accessed via the following link: 
http://researchintegrity.weill.cornell.edu/forms and policies/forms/Immediate Reportin 
g Policy.pdf. 
 
9.2 
Definition of SAE 
 
SAE’s include death, life threatening adverse experiences, prolonged hospitalization, disability 
or incapacitation, overdose, congenital anomalies and any other serious events that may 
jeopardize the subject or require medical or surgical intervention to prevent one of the 
outcomes listed in this definition. 
9.2.1 
Reporting of SAE to IRB 
 
All SAEs occurring on this study will be reported to the IRB according to the IRB policy, which 
can be accessed via the following link: 
http://researchintegrity.weill.cornell.edu/forms and policies/forms/Immediate Reporting P 
olicy.pdf. 
10 
Data and Safety Monitoring Plan (DSMP) 
The study will be monitored internally by the study teams in Radiation Oncology and Urology. 
Adverse events will be reviewed at every dose level. 
The WCMC Data and Safety Monitoring Board (DSMB) is the central monitoring board for this 
study. The WCMC Cancer Institute DSMB is the local monitoring board for WCMC patients. 
This study will be conducted in accordance with the guidelines in the 2001 NCI approved data 
Safety and Monitoring plan for the WCMC Cancer Institute and with the WCMC approved data 
Safety and Monitoring plan for the WCMC Cancer Institute. Reports to the DSMB will include 
the following information: accruals, targets, responses, adverse events and evidence of 
reporting to appropriate review committees. The WCMC Data and Safety Monitoring Board 
(DSMB) will review the IRB approved protocol, the data and safety monitoring plan and any 
stopping guidelines during protocol initiation. During the course of the study, the DSMB will 

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review cumulative study data twice a year to evaluate safety, efficacy, study conduct, and 
scientific validity and integrity of the trial. The WCMC DSMB may also convene as needed if 
stopping criteria are met or other safety issues arise that the Principal Investigator and/or IRB 
would like the WCMC DSMB to address. 
10.1 
DSMB safety Review 
 
Safety reports will be submitted to the DSMB every six months. 
10.2 
Stopping Rules 
 
For Part1, after completion of a dose level, if >=2 of 3, >=2 of 6 or >=3 of 9 patients develop 
develop a post-operative gastrointestinal or urinary grade 3 or higher toxicity at 30 days 
related to preoperative radiotherapy, the trial will accrue patients to the previous lower dose 
level. If >=2 of 3, >=2 of 6 or >=3 of 9 patients develop a post-operative gastrointestinal or 
urinary grade 3 or higher toxicity at 30 days related to preoperative radiotherapy at 5 Gy x 5 
fractions, the trial will stop. During Part 2, the study will stop if >=5 of 18, or 7 of 27 patients 
develop a post-operative gastrointestinal or urinary grade 3 or higher toxicity at 30 days 
related to preoperative radiotherapy at the R2PD. Adverse events at 30 days will be recorded 
based on according to the Clavien-Dindo Classification. 
If safety concerns arise, the DSMB will identify these concerns and recommend modification or 
termination of the clinical trial. There is no formal interim analysis for this trial. 

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11 
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