PSMA-PET for Biopsy and Treatment Guidance in Primary Prostate Cancer
Phase: PHASE2
Conditions: Prostate Cancer
Sponsor: Indiana University

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The Role of 68Ga-PSMA-11 PET in MRI Fusion Biopsy  
and Surgery Guidance in Prostate Cancer 
 
INDIANA UNIVERSITY PROTOCOL  
IUSCC-0658/ IRB # 1805494415/ NCT03429244 
Principal 
Investigator: 
Clinton D. Bahler, MD, MS 
Assistant Professor of Urology 
Indiana University School of Medicine 
535 Barnhill Dr., Ste 150 
Indianapolis, IN 46202 
Cell: 317.313.5405 
Fax: 317.944.0174 
cdbahler@iupui.edu 
Co-investigators: 
Michael Koch, MD 
Professor of Urology 
mkoch2@IUHealth.org 
 
Mark Tann, MD 
Professor of Radiology 
matann@iupui.edu 
 
Mark Green, PhD 
Professor of Radiology 
magreen@iu.edu 
 
Gary Hutchins, PhD 
Professor of Radiology, Vice Chair of Research 
gdhutchi@iupui.edu 

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Liang Cheng, MD 
Virgil H. Moon Professor of Pathology, Department of Pathology 
and Laboratory Medicine 
lcheng@iu.edu; liang_cheng@yahoo.com 
 
Temel Tirkes, MD 
Associate Professor of Radiology and Urology, Director of 
Genitourinary Radiology 
atirkes@iupui.edu 
 
Jason Parker, PhD 
Associate Professor, Director of Diagnostic Physics, Dept. 
of Radiology 
parkerjg@iu.edu 
 
Yang Zong, PhD 
Assistant Professor of Biostatistics 
zangy@iu.edu 
 
Yan Tong, PhD, MS 
Biostatistician, Department of Biostatistics 
tongy@iu.edu 
 
Justin Sims, MD 
Assistant Professor of Clinical Radiology 
simsjb@iupui.edu  
 
 
 
Support: 
Indiana University Departments of Urology, Radiology, and 
Pathology 
IND#: 
141706 
Date of Protocol: 
January 30, 2020 
 
 

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INVESTIGATOR’S AGREEMENT 
By signing below, I confirm that I have read this protocol and agree: 
• To assume responsibility for the proper conduct of this study at this site 
• To conduct the study according to the procedures described in this protocol 
and any future amendments 
• Not to implement any deviation from, or changes to, the protocol without written 
approval from the Institutional Review Board (IRB), except where necessary to 
eliminate immediate hazard to the subject(s) 
• That I am aware of all updates and will comply with all applicable regulations 
and guidelines 
 
 
 
Principal investigator’s signature 
 
Date 
Clinton D. Bahler, MD, MS 
 
 
Principal investigator’s name (print) 
 
 
Assistant Professor of Urology,  
Indiana University School of Medicine 
 
 
 
Principal investigator’s title (print) 
 
 
 
 

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PROTOCOL SYNOPSIS 
Primary 
Objectives: 
Define the accuracy of 68Ga-PSMA-11 PET-CT for detecting the 
location and size of clinically significant prostate cancer lesions in 
low and intermediate risk disease. 
Secondary 
Objectives: 
Evaluate how knowledge of the PSMA-PET might inform treatment 
planning. 
Exploratory 
Objectives: 
Generate pilot data to be validated in larger studies 
 
Study Design: 
Prospective, early phase clinical trial, single arm 
Test 
Factor/Exposur
e: 
Intravenous injection of 68Ga-PSMA-11 and detection with PET-CT 
scanner 
Duration of 
Treatment: 
Patients will undergo injection of 68Ga-PSMA-11 PET-CT and pre-
treatment MRI scan and followed until biopsy and/or surgical 
resection.   
 
Enrollment: 
Subject accrual is planned for 24 months 
Inclusion 
Criteria: 
1. ≥ 18 years of age 
2. Must provide written informed consent 
3. Presence of low or intermediate risk prostate cancer or at risk 
of having intermediate risk cancer 
a.  Intermediate risk prostate cancer: 
i. Grade group 2 = 3 + 4, or 
ii. Grade group 3 = 4 + 3 
b.  At Risk of intermediate risk prostate cancer: 
i. 4K score  ≥ 20%, or 
ii. Select MDx ≥ 20%, or 
iii. PSA Density ≥ 0.15 
iv. Grade group 1= 3+3 
4. Scheduled for MRI or has recently completed SOC MRI 
(within 6 months) for further biopsy, surgical removal or focal 
therapy. 
5. Willing and able to lie still for approximately 50 minutes in an 
enclosed space for the CT 

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Exclusion 
Criteria: 
1. Participation in another investigational trial involving research 
exposure to ionizing radiation concurrently or within 30 days. 
2. Does not meet safety criteria for MRI scan (e.g. metal implant 
that is not allowed). 
3. Significant acute or chronic medical, neurologic, or  
     illness in the subject that, in the judgment of the Principal    
     Investigator, could compromise subject safety, limit the  
     ability to complete the study, and/or compromise the 
objectives of the study. 
Number of 
Subjects: 
36 patients 
Number of 
Sites: 
Indiana University Simon Cancer Center, Indiana University Health 
Hospital, IU Health North, IU Health North medical office building, IU 
Health Methodist Hospital 
Primary 
Outcome: 
Sextant based analyses using prostatectomy whole-mount analysis 
or biopsy as Gold Standard: 
1) Sensitivity, specificity, Receiver operator curve (ROC) of 
mpMRI for each Gleason pattern (3, 4, 5) 
2) Sensitivity, specificity, ROC of PSMA PET-CT for each 
Gleason pattern (3, 4, 5) 
 
Secondary 
Outcomes: 
1. Lesion based analysis of accuracy 
2. For 3+4: Sensitivity and specificity of mpMRI based on 
Gleason %pattern 4 
3. For 3+4: Sensitivity and specificity of PET-CT based on 
Gleason %pattern 4 
4. Sensitivity and specificity for extra-capsular extension 
(mpMRI vs PET-CT) 
5. Sensitivity and specificity for seminal vesicle invasion 
(mpMRI vs PET-CT) 
6. Impact of PSMA PET-CT on treatment plan for surgery: 
a. Additional lesions found, additional sextants involved, 
extra-capsular extension detected, seminal vesicle 
invasion detected, lymph node invasion detected. 
7. Impact of PSMA PET-CT on treatment plan for biopsy: 
a. Additional lesions found, additional sextants involved  
 
 
 

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1 
TABLE OF CONTENTS 
INVESTIGATOR’S AGREEMENT .................................................................................................................................... 3 
PROTOCOL SYNOPSIS ...................................................................................................................................................... 4 
1 
TABLE OF CONTENTS .............................................................................................................................................. 6 
2 
SCHEMA ......................................................................................................................................................................... 8 
3 
BACKGROUND ............................................................................................................................................................. 9 
3.1 
BACKGROUND & PRELIMINARY WORK ................................................................................................................................ 9 
3.2 
RATIONALE ................................................................................................................................................................................. 13 
4 
STUDY OBJECTIVES ............................................................................................................................................... 14 
4.1 
PRIMARY ..................................................................................................................................................................................... 14 
4.2 
SECONDARY .............................................................................................................................................................................. 14 
4.3 
EXPLORATORY .......................................................................................................................................................................... 14 
5 
ELIGIBILITY CRITERIA ............................................................................................................................................ 14 
5.1 
INCLUSION CRITERIA .............................................................................................................................................................. 14 
5.2 
EXCLUSION CRITERIA ............................................................................................................................................................. 15 
6 
PATIENT REGISTRATION ...................................................................................................................................... 15 
7 
STUDY PROCEDURES ............................................................................................................................................ 16 
7.1 
SUMMARY ................................................................................................................................................................................... 16 
7.2 
STUDY CALENDAR ................................................................................................................................................................... 17 
7.3 
ASSESSMENTS BY VISIT ........................................................................................................................................................ 19 
8 
STUDY WITHDRAWAL/DISCONTINUATION ................................................................................................... 22 
9 
STATISTICAL CONSIDERATIONS ...................................................................................................................... 23 
9.1 
STUDY DESIGN ......................................................................................................................................................................... 23 
9.2 
STUDY POPULATION ............................................................................................................................................................... 23 
9.3 
SAMPLE SIZE ............................................................................................................................................................................. 23 
9.4 
STUDY ENDPOINTS ................................................................................................................................................................. 24 
9.5 
PARTICIPANT CHARACTERISTICS ....................................................................................................................................... 24 
9.6 
CONCOMITANT MEDICATIONS ............................................................................................................................................. 24 
9.7 
ANALYSIS OF PRIMARY OBJECTIVE ................................................................................................................................... 25 
9.8 
ANALYSIS OF SECONDARY OBJECTIVES ......................................................................................................................... 25 
10 
DATA FORMS AND SUBMISSION SCHEDULE ......................................................................................... 25 
11 
DATA AND SAFETY MONITORING PLAN ................................................................................................... 25 
11.1 
IND ANNUAL REPORTS ......................................................................................................................................................... 26 
11.2 
STUDY AUDITING AND MONITORING ................................................................................................................................. 27 

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11.3 
DATA MANAGEMENT/ONCORE REPORTING REQUIREMENTS ................................................................................. 27 
11.4 
ONCORE SAFETY REPORTING ........................................................................................................................................... 27 
11.5 
STUDY ACCRUAL OVERSIGHT ............................................................................................................................................. 27 
11.6 
PROTOCOL DEVIATION REPORTING ................................................................................................................................. 27 
12 
ADVERSE EVENTS .............................................................................................................................................. 28 
12.1 
DEFINITIONS OF ADVERSE EVENTS .................................................................................................................................. 28 
12.2 
ADVERSE EVENT REPORTING REQUIREMENTS: .......................................................................................................... 29 
13 
PATIENT CONSENT AND PEER JUDGEMENT ......................................................................................... 30 
14 
REFERENCES ........................................................................................................................................................ 30 
15 
APPENDICES ......................................................................................................................................................... 33 
15.1 
APPENDIX A ............................................................................................................................................................................... 33 
15.2 
APPENDIX B ............................................................................................................................................................................... 34 
15.3 
APPENDIX C ............................................................................................................................................................................... 36 
15.4 
APPENDIX D ............................................................................................................................................................................... 37 
 
 

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2 
SCHEMA  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
While the total N=36 for this trial, the number of subjects enrolled on each arm (prostatectomy vs. surveillance) 
is not required to be divided evenly.  

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3 
BACKGROUND 
3.1 
Background & Preliminary Work 
Up to 60% of men in the U.S. unwittingly have Gleason 6 (pure pattern 3: 3+3) prostate 
cancer by their 80s on autopsy, which argues for active surveillance of this tumor 
(Zlotta, et al. 2013).  Long-term active surveillance cohorts demonstrate low (<5%) 15-
year metastasis rates (Musunuru, et al. 2017).  However, <50% choose active 
surveillance when diagnosed on biopsy with Gleason 6 prostate cancer (Womble, et al. 
2015).  This is due to multiple factors: (1) prostate cancer is multi-focal in >80%; (2) 
prostate cancer commonly has mixed grade lesions; and (3) conventional imaging 
modalities (US, MRI) miss significant cancer. There is also disagreement on what 
follow-up is needed during active surveillance. Molecular imaging agents would bring 
assurance and peace of mind to hundreds of thousands of men, if they are capable of 
selectively detecting clinically significant prostate cancer (Gleason patterns 4 and 5).  
We expect to determine whether the PSMA-targeted PET agent, 68Ga-PSMA-11, 
reliably detects significant prostate cancer and what minimum percentage Gleason 
pattern 4 is required for detection by comparison of PET/MR to whole mount analysis. 
Multiparametric 3-T MRI has shown the ability to locate prostate cancer lesions that are 
higher grade and increased size. For example, MRI-targeted biopsy increases the 
detection of clinically significant prostate cancer using fewer cores than template biopsy 
(Pokorny, et al. 2017, Wysock, et al. 2014), while reducing detection of insignificant 
Gleason 6. However, recent studies mapping MRI lesions to final whole-mount 
pathology show limitations.  For example, a recent study showed only 80% of index 
(largest) tumors were seen by MRI and even fewer clinically significant non-index 
lesions (Le, et al. 2014).  Another recent study showed MRI missed a clinically 
significant lesion in 26% of patients using whole-mount analysis (Borofsky, et al. 2017).  
Fittingly, Borofsky titled their paper, “What are we missing? False negative cancers at 
Multiparametric MR imaging of the prostate.”  MRI interpretation has also been shown 
to vary substantially across radiologists, which persisted after correcting for radiologist 
practice volume (Sonn, et al. 2017).  Therefore, the majority of urologists still take 
ultrasound-based template biopsies at the time of MRI guided biopsy (MRI-ultrasound 
fusion). 
The status quo for pathologic assessment is Gleason Grading, which combines the two 
dominant Gleason patterns and sometimes lists a tertiary pattern. Gleason grading 
might be sufficient when treating the whole gland: surgery, radiation, cryotherapy, etc.  
However, conventional Gleason grading gives insufficient detail when considering active 
surveillance or focal therapy because the Gleason grade combines all the lesions into a 

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single score and is not lesion specific.  For example, a prostate with three cancer 
lesions might be reported as Gleason 3 + 4 (90%/10%) on final pathology while the 
individual lesions are:  (1) 3 + 4 + 5 (30%/60%/10%), (2) 3 + 4 (90%/10%), (3) 3 + 3. 
Lesion (1) is clinically significant while lesion (3) is not.  Lesion (2) is of debatable 
significance and requires further study.  Certainly, the above 3-lesion cancer is different 
than a single lesion 3+4 cancer despite the same grading. A detailed lesion-specific 
analysis is required to accurately assess new imaging agents and ultimately to test the 
paradigm of focal organ-sparing therapy.  The proposed research is innovative, in our 
opinion, because we perform lesion and intra-lesion specific analyses while testing 
68Ga-PSMA-11 with PET-CT.  This requires researchers with experience in lesion 
specific prostate cancer pathology, mpMRI and PET imaging, and focal therapy. Finally, 
we feel the study design is innovative because it incorporates PSMA PET-CT imaging 
into the standard clinical workflow.  This enables pilot data using the current standard-
of-care as the control; the goal is to facilitate translation of molecular imaging more 
quickly to clinical care.   
Whole mount pathologic analysis of PET imaging in prostate cancer has been reported 
primarily out of Germany.  No prospective trials were found combining PSMA, PET-CT, 
and whole-mount analysis.  Furthermore, studies have focused on high-risk disease 
rather than low/intermediate risk.  For example, a retrospective trial out of Germany 
(Eiber, et al. 2016) combined 68Ga-PSMA-11 and PET-CT and found improvement in 
Receiver operator curve (ROC) for PET-CT over MRI (0.73 to 0.88, p<0.001).  Of the 53 
patients, 53% were high risk.  The authors concluded prospective studies were 
warranted for biopsy guidance.  Recently, 18F-FACBC (Fluciclovine) was used with 
PET-CT and compared to MRI for biopsy guidance in a prospective clinical trial 
(Jambor, et al. 2017).  18F-FACBC had high sensitivity (87%), but low specificity (56%) 
resulting in a low ROC (0.72).  18F-FACBC is not specific for prostate cancer resulting in 
replacement with PSMA-based tracers in clinical practice. 
The Urology-Radiology-Pathology team at Indiana University has been employing 
fusion biopsy since 2013 and has performed more than 600 during this time.  A recent 
abstract presented at the annual meeting of the American Urologic Association in 2017 
demonstrated 22% of index lesions (largest tumor) were missed by MRI (Bahler, et al. 
2017), and MRI undersized the index cancer lesion when compared to final pathology 
(2.2cm vs. 1.9cm, p = 0.03).  A tracer that is both more sensitive and specific is desired 
leading urologists to continue ultrasound template biopsies with MRI targeted biopsy. 
The 68Ga-PSMA-11 (HBED-CC) radiopharmaceutical (Eder, et al. 2014; Eiber, et al. 
2015, Afshar-Oromieh, et al. 2015) is structurally based on a class of urea-derived 
inhibitors of PSMA (Pillai, et al. 2016). The targeting peptide has been modified at its N-
terminus to incorporate the HBED-CC chelating agent with an exceptionally high binding 
affinity (~1039) for the Ga3+ ion (Figure 1 and Table 1). Methods for on-demand 

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production of 68Ga-PSMA-11 are already established (IND # 131,806), based on our 
research use of this radiopharmaceutical in imaging patients with recurrent prostate 
cancer. 
Table 1. PSMA Affinities of the PSMA-11 Agent Before, and After, Ga3+ Chelation 
PSMA Ligand 
IC50 (nM) 
PSMA-11  HBED-CC 
5.7 ± 0.5 
Ga-PSMA-11 HBED-
CC 
6.1 ± 0.8 
 
Figure 1. Structure of the PSMA-11 
(HBED-CC) conjugate employed in 
preparation of the 68Ga-PSMA-11 
radiopharmaceutical. The PSMA-11 has a 
molecular weight of 947 g/mol. The 
radiopharmaceutical synthesis protocol for 
on-demand production of 68Ga-PSMA-11 
employs 10-µg of the PSMA-11 conjugate 
per batch. 
 
 
The project investigators have significant experience in PET with 68Ga-PSMA-11. Our 
initial human experience with 68Ga-PSMA-11 PET was in performing patient imaging for 
dosimetry assessment, studying ten prostate cancer patients with biochemical 
recurrence who had been previously clinically imaged with 11C-acetate under an 
Expanded Access IND (Green, et al. 2017). The expected utility of 68Ga-PSMA-11 PET 
was apparent even in that limited series, with 68Ga detection of sites of metastasis that 
were not apparent in 11C-acetate imaging (Figure 2).  We have subsequently dropped 
11C-acetate imaging in prostate cancer patients with biochemical recurrence in favor of 
68Ga-PSMA-11 PET, and have performed clinical imaging on over 100 patients under 
Expanded Access IND 131,806.  When evaluating the first 70 68Ga-PSMA-11 PET 
scans, we found improved detection (p<0.05) over 11C-acetate PET at PSA-values >2 
(abstract accepted to America Urologic Association 2018 national meeting). 
We have also recently completed a prospective clinical trial evaluating 68Ga-PSMA-11 
whole-body PET-CT in 10 patients with biopsy-proven high-risk prostate cancer.  The 
PET-CT was obtained prior to scheduled surgical resection for correlation of imaging 

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findings with whole-mount pathology. These subjects also received a second 68Ga-
PSMA-11 dose intraoperatively to allow in vitro high-resolution PET assessment of 
tracer binding within the resected tissue. All staging 68Ga-PSMA-11 PET/CT scans 
showed suspicious prostate lesions with median (IQR) of 10.6 SUV (8-14); benign 
prostate had a median (IQR) of 3.8 SUV (3-5).  Four staging 68Ga-PSMA-11 PET-CT 
scans showed seminal vesicle invasion, and two showed nodal involvement; all were 
confirmed on final pathology.  
Indiana University performed >1,000 robotic prostatectomies over the past four years 
and >600 MRI-fusion biopsies during the same span.  This clinical volume will provide 
adequate numbers for trial accrual (n=36).  There are currently no competing trials for 
our study population. The investigators (Koch, Bahler) and clinical trial coordinator 
(Beasley) will identify patients in the Indiana University urology clinic and 
inclusion/exclusion criteria will be assessed prior to informed consent 
Figure 2:  68Ga-PSMA-11 PET/CT demonstrated avid lymph nodes (A) and bony 
metastasis (B) not seen with the 11C-acetate PET/CT.  The PSA was 1.7 and 11.1, 
respectively. During the recent clinical trial, a PET-CT scanner was installed at Indiana 
University allowing us to compare PET-CT to PET-MRI (Figure 3).  MRI has far superior 
soft-tissue contrast compared to the CT, which cannot identify the lesions within the 
prostate gland by itself, and cannot qualify as a “one-stop-shop” examination. Integrated 
utilization of PSMA PET and MRI has paramount implications for the improved 
diagnostic pathway of the prostate cancer. In addition to the better diagnostic potential, 
there is also a potential for significantly reduced cost of the total diagnostic workup of 
the prostate cancer using a single examination (i.e., PSMA PET-CT) compared to 
having a mpMRI, PSMA PET study, and a bone scan. We hypothesize the improved 

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soft tissue resolution will improve biopsy accuracy and surgical planning when 
compared to PET-CT. 
 
 
 
 
 
 
 
Figure 3: The PET-CT (A) shows much more soft tissue detail within the prostate when 
compared to the PET-CT (B) on the same patient.  
3.2 
Rationale 
Our long-term goal is to improve cancer outcomes and quality of life for prostate cancer 
patients by bringing novel imaging agents and systems to the diagnosis and treatment 
of prostate cancer. The overall objective of this Early Phase Clinical Trial is to begin 
defining the accuracy of 68Ga-PSMA-11 for detecting the location and size of clinically 
significant prostate cancer lesions in low and intermediate risk disease. 
The proposed studies will be performed with a state-of-the-art Vision PET-CT system 
which offers unprecedented spatial resolution and counting sensitivity for a clinical PET 
system that make it ideal for supporting biopsy and focal therapy decisions.  We 
propose detailed intra-lesion whole-mount pathologic analysis as the gold standard for 
critically assessing PSMA PET accuracy in patients undergoing surgery, and blinded 
PSMA PET-CT comparison with standard multi-parametric MRI (mpMRI) for patients 
having biopsy on active surveillance. This intensive testing of the accuracy and value of 
PSMA-based tracers requires our unique collaboration of surgeons, radiologists, 
pathologists, and imaging scientists with decades of experience and innovation. 

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4 
STUDY OBJECTIVES 
4.1 
Primary 
Define the accuracy of 68Ga-PSMA-11 PET-CT for detecting the location and size of 
clinically significant prostate cancer lesions in low and intermediate risk disease. 
4.2 
Secondary 
Evaluate how knowledge of the PSMA-PET can inform treatment planning. 
4.3 
Exploratory 
Generate pilot data for future larger clinical trials 
5 
ELIGIBILITY CRITERIA 
5.1 
Inclusion Criteria 
To be considered eligible to participate in this study, a patient must meet all the 
inclusion criteria listed below: 
1. ≥ 18 years of age 
2. Must provide written informed consent 

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3. Presence of low or intermediate risk prostate cancer or at risk of having 
intermediate risk cancer 
a.  Intermediate risk prostate cancer: 
i. Grade group 2 = 3 + 4, or 
ii. Grade group 3 = 4 + 3 
b.  At Risk of intermediate risk prostate cancer: 
i. 4K score  ≥ 20%, or 
ii. Select MDx ≥ 20%, or 
iii. PSA Density ≥ 0.15 
iv. Grade group 1= 3+3 
Note: Where multiple cancer lesions are present on biopsy, it is allowable to have 
Gleason 8 or 9 cancer lesions if they are in addition to the intermediate risk cancer as 
described above. 
4. Scheduled for MRI or has recently completed SOC MRI (within 6 months) for 
further biopsy, surgical removal, or focal therapy. 
5. Willing and able to lie still for approximately 50 minutes in an enclosed space for 
the CT. 
5.2 
Exclusion Criteria 
1. Participation in another investigational trial involving research exposure to 
ionizing radiation concurrently or within 30 days. 
2. Does not meet safety criteria for MRI scan (e.g. metal implant that is not 
allowed). 
3. Significant acute or chronic medical, neurologic, or psychiatric illness in the 
subject that, in the judgment of the Principal Investigator, could compromise 
subject safety, limit the subject’s ability to complete the study, and/or 
compromise the objectives of the study. 
6 
PATIENT REGISTRATION 
Patient enrollment will take place over 24 months at a single institution – Indiana 
University Simon Cancer Center (IUSCC) encompassing Indiana University Hospital 
(IUH), IU Health North, IU Health North medical office building, IU Health Methodist 
Hospital. Potential patients will be identified in the Urology clinic, or by physician 
referrals, mostly likely but not exclusively during pre-operative consultations for biopsy 
or surgical removal of prostate cancer. All study procedures will take place at 
IUSCC/IUH/IU-Health Methodist Hospital, with the research imaging performed at the IU 
Health Goodman Hall outpatient facility.  All patients will be registered with the Indiana 
University (IU) Department of Urology. Regulatory files will be maintained by the 
Department of Urology. Applicable regulatory documents must be completed and on file 

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prior to registration of any patients. Patients who appear to be eligible for this trial will 
undergo the Informed Consent Process and be screened for eligibility utilizing the 
Eligibility Criteria. Individual patient registration will be done in the REDCap database. 
The original signed Institutional Review Board (IRB) approved Informed Consent 
Document and completed eligibility checklist will be stored in the following location: 
Indiana University Department of Urology, 535 N. Barnhill Dr., Ste 150, Indianapolis, IN, 
46202. 
7 
STUDY PROCEDURES 
7.1 
Summary 
This patient population will have low (1 = Gleason 3 + 3) or intermediate risk (2 = 3 + 4; 
3 = 4 + 3) prostate cancer, or be at risk of having intermediate disease as evidenced by 
a 4K score >20%, or Select MDx > 20%, or PSA Density > 0.15. Patients will be 
scheduled for a MRI as part of routine care for either surgical planning or for further 
biopsy. Following the informed consent process, patients who enroll in the study will 
receive a 68Ga-PSMA-11 PET study along with their standard of care (SOC) MRI on an 
PET-CT.  If the Vision PET-CT is not available, a standard PET-CT and SOC MRI can 
be done with co-registration of PET and MRI done using software to generate the 
equivalent of the PET-CT images.  Patients receiving SOC MRI guided biopsy will have 
the additional PET data factored into their guided biopsy plan.  The sensitivity and 
specificity for lesion characterization will be evaluated, along with the ability of the tracer 
to inform the treatment planning.  Patients receiving surgical removal of the prostate will 
have a slice-by-slice whole mount analysis to assess the sensitivity and specificity the 
PSMA PET.

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7.2 
Study Calendar 
  
Screening/ 
Baseline 
(-180 days) 
Biopsy 
if indicated 
Imaging 
Surgery 
if indicated 
REQUIRED ASSESSMENTS 
 
 
 
 
Informed Consent 
X 
 
 
 
Inclusion/Exclusion 
X 
 
 
 
Medical History1 
X 
 
 
 
PSMA dose and PET scan 
 
 
X2 
 
SOC MRI 
 
 
 
 
SOC MRI-guided biopsy 
 
X 
 
 
SOC PET-guided biopsy 
 
X 
 
 
SOC Focal Therapy 
 
 
 
X 
Pathologic assessment of biopsy 
 
X 
 
 
SOC prostatectomy 
 
 
 
X 
Pathologic assessment of whole mount 
 
 
 
X 

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Footnotes: 
1. Medical history may be obtained via medical records, as necessary. 
2. A second 68Ga-PSMA-11 PET, approximately 6-12 months following initial scan may be requested, if: (1) the subject undergoes HIFU 
treatment and/or (2) during follow-up, is rescheduled for MRI-fusion biopsy as standard of care. 

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7.3 
Assessments by Visit 
7.3.1 Baseline/Screening (within 6 months of scan(s)/biopsy): 
• Informed consent: investigators or their designees will discuss with subjects the 
nature of the study, its requirements, risks, and restrictions to obtain informed 
consent for participation in the study. Subjects should have sufficient time to 
review the study information and consent form and to ask any questions 
necessary to make an informed decision regarding their participation in the study. 
Written informed consent is to be obtained before any other study-specific 
procedure. 
 
• Eligibility criteria: make sure patient meets study eligibility criteria. 
• Demographics: track sex, race, ethnicity, date of birth, address, etc. 
• Medical history: includes past medical history, past surgical history, allergies, any 
ongoing medical conditions, and including medications noted in patients record at 
time of screening 
7.3.2 Imaging 
• Eligibility criteria: ensure subject continues to meet study eligibility (if longer than 
60 days since screening) 
• Medical history: capture additional medical history since screening (if longer than 
60 days since screening) 
• Concomitant medications: record medications taken since screening through day 
of surgery (if longer than 60 days since screening) 
• There will be a ≥4week wait period between prior biopsy and protocol related MR 
imaging to allow for resolution of hematomas. 
• 
68Ga-PSMA-11 PET-CT and mpMRI:   

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o Patient receives a ~3-5 mCi dose of 68Ga-PSMA-11. (A physician-
sponsored IND has been successfully obtained) 
o Patient will undergo research Vision PET-CT and SOC MRI at Goodman 
Hall (or similar facility) which is anticipated to last approximately 60 
minutes.  Per our institutional standard of care, patients will receive 
intravenous iodinated contrast with the PET-CT unless medically 
contraindicated. 
o Imaging Protocol for 68Ga-PSMA-11 PET Data Acquisition (approximate 
times): 
 
Time 
(minutes) 
Activity 
- 60 
Patient arrives, and completes consent forms, while radiopharmaceutical synthesis and 
quality control procedures are completed. 
0 
Administer 68Ga-PSMA-11, 3-5 mCi (outside the camera). 
5-50 
Start standard-of-care pelvic MR acquisition with simultaneous collection of 68Ga-
PSMA-11 PET. 
50-55  
Patient can leave camera and depart. 
o The PET read will be done by a board certified nuclear medicine 
specialist (e.g. Mark Tann, MD or similar) and the MRI read will be done 
by a board certified MR radiologist (e.g. Temel Tirkes, MD or similar).  
Suspicious lesions will be marked in a blinded fashion. 
o AE assessment: AEs will be assessed at the time of 68Ga-PSMA-11 
administration and also at the appointment for biopsy (if done) any event 
not expected is collected including but not limited to: rash and shortness 
of breath. 
o Safety monitoring following radiopharmaceutical administration will 
consist of visual and verbal monitoring of the patent after injection, and 
during and at the conclusion of the PET/CT procedure, with any apparent 
patient abnormalities, reactions or reported effects noted in the study 
records. 
o The nuclear medicine technologists administering the 
radiopharmaceutical are responsible for immediately reporting any 
adverse or unexpected events to the principal investigator or clinical 

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designee, who will report the occurrence of any adverse events to the 
IRB. 
o As in most clinical nuclear medicine procedures, these 
radiopharmaceuticals are administered at a sub-pharmacologic 
doses.  Adverse events are exceedingly unlikely, as 68Ga-HBED-CC has 
been clinically employed, extensively and without reported incident, 
in  clinical patient diagnostic imaging studies in prostate cancer patients in 
Germany and other European countries, as well as in over 100 patients 
locally.  
o If there is a discrepancy between the PSMA and conventional MRI scan, 
the investigators will discuss the treatment plan with the patient at the 
investigator’s discretion.  
o If the patient does not undergo a prostatectomy, no further study 
procedures will be performed. 
o If the Vision PET-CT is not available, a standard PET-CT and mpMRI 
may be done with software registration of PET and MR images. 
o A patient may have a second 68Ga-PSMA-11 PET, approximately 6-12 
months following initial scan, if: (1) the patient undergoes HIFU treatment 
and/or (2) during follow-up, is rescheduled for MRI-fusion biopsy as 
standard of care.  
7.3.3 PET, MRI Biopsy: 
• Patients proceeding to surgery following PSMA PET and MRI may forgo biopsy. 
• Patients not proceeding to surgery will undergo a SOC MRI-fusion biopsy based 
on the pre-biopsy scan detailed in 7.3.2.  PET findings will be integrated into the 
planning of the fusion biopsy.  See appendix C for details of the fusion biopsy. 
• AE assessment: AEs will be assessed at the time of 68Ga-PSMA-11 
administration and also at the appointment for biopsy (if done) any event not 
expected is collected including but not limited to: rash and shortness of breath. 
• A sextant-based analysis will be performed. See appendix D for details of sextant 
analysis. 
• A secondary “per lesion” analysis will also be performed. 

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• How the knowledge of the PSMA-PET informs treatment will be tracked.  
Examples of informing the decision include PSMA-PET detected additional 
intraprostatic cancer lesions diagnosed. 
7.3.4 Surgery and Pathology 
• The standard of care surgical procedure is performed as indicated by the cancer. 
• Pathologic assessment: whole mount sections of prostate tissue and routine 
sections of lymph nodes if applicable will be fixed and analyzed by licensed 
pathologist per routine care.  This typically happens within 2 weeks of 
prostatectomy. 
• Additional study-related pathologic assessment: intraprostatic lesion-based 
assessment will be done to document the % Gleason pattern 3, 4, and 5 within 
each lesion. 
• A sextant-based analysis will be performed.  See appendix D for details of 
sextant analysis. 
• A secondary “per lesion” analysis will also be performed. 
• How the knowledge of the PSMA-PET informs treatment will be tracked. 
Examples of informing the decision include the number and location of 68Ga-
PSMA-PET detected: additional intraprostatic cancer lesions diagnosed, extra-
prostatic extension, seminal vesicle invasion, and lymph node invasion. 
• Genomic studies (e.g. Decipher, mRNA sequencing, or similar) may be done as 
standard of care for medical management following biopsy or surgery or may be 
done for determining association of mRNA (e.g. FOLH1 or others) and imaging 
characteristics. 
8 
STUDY WITHDRAWAL/DISCONTINUATION 
Subjects must be discontinued from the study for the following reasons: 
• Withdrawal of consent 
• Investigator deems withdrawal necessary at any time if it is determined that it is 
not in the subjects best interest to continue, or if the subject is found to be 
noncompliant with study procedures. 

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If subject discontinues after administration of study drug, he or she will be encouraged 
to continue on study for safety procedures per protocol. Reason(s) for discontinuing 
must be clearly documented in the appropriate source documents. 
9 
STATISTICAL CONSIDERATIONS 
9.1 
Study Design 
Prospective, phase 2 clinical trial, single arm 
9.2 
Study Population 
The enrolled population comprises all patients who meet the eligibility criteria and are 
registered onto the study. 
9.3 
Sample Size 
Table 1: Sample size calculation: 
 
sensitivity= 
0.80 
sensitivity= 
0.85 
sensitivity= 
0.90 
sensitivity= 
0.95 
Error allowed (d)= 7.5% 
46 
37 
27 
14 
Error allowed (d)= 10% 
27 
21 
15 
8 
 
Our sample size is based on the key primary endpoint of sensitivity to detect clinically 
significant (Gleason >6 and >5mm) cancer overall. In the Table above we summarized 
the sample size required to achieve a certain degree of accuracy for different sensitivity 
levels. All the calculations are based on the normal approximation of the binomial 
distribution. For this pilot, we will also assume the samples within each patient are 
independent statistically. Each patient has six samples for diagnostic testing (sextants) 
and the prevalence of cancer per sextant is estimated to be 40% (Eiber et al., 2016). 
The rows (d) present the marginal maximal error under 95% confidence interval and the 
columns represent the sensitivity rate. The numbers in Table 1 represent the required 
number of patients needed for each different combination of marginal error (d) and 
sensitivity rate. In other words, for a sensitivity of 90% and a marginal error of 7.5%, we 

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are 95% sure that the sensitivity lies between 82.5% and 97.5% if we enroll 27 patients. 
Based on Table 1, the maximal sample size is 46 assuming the sensitivity is 
80%.  Therefore, we decided 36 patients was adequate to ensure that the proposed trial 
can achieve certain accuracy of the sensitivity across the majority the scenarios 
considered in Table 1.  
9.4 
Study Endpoints 
9.4.1 Primary 
Sextant based analyses using prostatectomy whole-mount analysis or biopsy as 
Gold Standard (Appendix D): 
• Sensitivity, specificity, Receiver operator curve (ROC) of mpMRI overall and for 
each Gleason pattern (3, 4, 5) 
• Sensitivity, specificity, ROC of PSMA PET-CT overall and for each Gleason 
pattern (3, 4, 5) 
9.4.2 Secondary 
• Lesion based analysis of accuracy 
• For 3+4: Sensitivity and specificity of mpMRI based on Gleason %pattern 4 
• For 3+4: Sensitivity and specificity of PET-CT based on Gleason %pattern 4 
• Sensitivity and specificity for extra-capsular extension (mpMRI vs PET-CT) 
• Sensitivity and specificity for seminal vesicle invasion (mpMRI vs PET-CT) 
• Impact of PSMA PET-CT on treatment plan for surgery: 
o Additional lesions found, Additional sextants involved, extra-capsular 
extension detected, seminal vesicle invasion detected, lymph node 
invasion detected. 
• Impact of PSMA PET-CT on treatment plan for biopsy: 
o Additional lesions found, Additional sextants involved 
9.5 
Participant Characteristics 
Demographic characteristics will be summarized using descriptive statistics. 
9.6 
Concomitant Medications 
Concomitant medications will be coded using the WHO Drug dictionary and will be 
summarized in tabular format. 

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9.7 
Analysis of Primary Objective 
We will use the generalized estimation equation (GEE) to fit the data and estimate the 
sensitivity and specificity. We will use the receiver operating characteristic (ROC) curve 
to represent the values of sensitivity and specificity at different thresholds (PET= SUV, 
mpMRI=suspicion scores). According to the ROC curve, we will determine the optimal 
threshold with a minimal sensitivity of 50% by maximizing the Youden index. We will 
use the McNemar test to compare the sensitivity and specificity values between PET 
and MRI although data from this pilot study is considered hypothesis generating only 
due to the small sample size. In addition, we will use the bootstrapping method to detect 
the significant difference of the area under curve (AUC) with different ROC curves. 
9.8 
Analysis of Secondary Objectives 
The proportion of patients who had cancer detected by both the standard of care 
imaging (MRI) and the 68Ga-PSMA-11 PET imaging will be calculated, along with exact 
95% confidence intervals. A similar approach will be used for other secondary outcomes 
in Section 9.4.2 to compare the cancer detection of the mpMRI and  68Ga-PSMA-11 
detection method to the surgical observations and the clinical tissue histopathology 
findings. 
10 
DATA FORMS AND SUBMISSION SCHEDULE 
This study will utilize the secure, web-based, Research Electronic Data Capture 
(REDCap) system for data input.  REDCap was developed by Vanderbilt University and 
is provided by Indiana University through their community license.  REDCap is 
managed by the Indiana University Department of Biostatistics and secured by 
University Information Technology Services Advanced IT Core.  Access to the password 
protected database will be limited to the investigators of this study, and any data that is 
distributed will be either de-identified or authorized by written permission from the 
subject. 
All source documents are to remain in the patient’s clinic file.  All documents should be 
kept according to applicable federal guidelines.  
11 
DATA AND SAFETY MONITORING PLAN 
This study will be conducted in accordance with the IU Simon Cancer Center 
Institutional DSMP for High Risk Trials.    
  

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Investigators will conduct continuous review of data and subject safety. Weekly review 
meetings for high risk trials are required and will include the principal investigator, 
clinical research specialist and/or research nurse (other members per principal 
investigator’s discretion). Weekly meeting summaries should include review of data and 
subject safety by including for each dose level: the number of subjects, significant 
toxicities as described in the protocol, dose adjustments and responses observed. 
Study teams should maintain meeting minutes and attendance for submission to the 
DSMC upon request.    
Data and Safety Monitoring Committee  
The IUSCC Data and Safety Monitoring Committee (DSMC) is responsible for oversight 
of subject safety, regulatory compliance, and data integrity for this trial.  The DSMC will 
review this study semi-annually to review overall trial progress, toxicity, compliance, 
data integrity, and accrual per the Institutional DSMP.    
  
Furthermore, the DSMC conducts an administrative review of serious adverse events 
(SAEs), deviations, reportable events, and any other outstanding business.  Major 
issues may require further DSMC review or action.    
  
For any increase in frequency of grade 3 or above adverse events (above the rate 
reported in the Investigator Brochure or package insert), the principal investigator will 
notify the DSMC Chair immediately.  The notification will include the incidence of study 
adverse events, grades, and attributions, as well as investigator statements regarding 
comparison with risks per the IB/ package insert.     
  
At any time during the conduct of the trial, if it is the opinion of the investigators that the 
risks (or benefits) to the subject warrant early closure of the study, the DSMC Chair and 
Compliance Officer must be notified within 1 business day via email, and the IRB must 
be notified within 5 business days. Alternatively, the DSMC may initiate suspension or 
early closure of the study based on its review. 
11.1 
IND Annual Reports 
For trials with an IND held locally by the IU principal investigator or university, the IND 
Annual Report will be prepared and submitted to the Compliance Team.  This report will 
be reviewed by the DSMC at the time of FDA submission.  

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11.2 
Study Auditing and Monitoring  
All trials conducted at the IUSCC are subject to auditing/monitoring. Reports will be 
forwarded to the DSMC for review.  
11.3 
Data Management/OnCore Reporting Requirements   
The DSMC reviews data and study progress directly from Oncore; therefore, timely data 
entry and status updates are vital.  Study data must be entered within Oncore promptly, 
no later than one week from study visit occurrence.  Subject status in Oncore will be 
updated in real time, as this may affect overall trial enrollment status.  Global SAEs and 
deviations will be reviewed on a monthly basis by the DSMC Chair directly from Oncore.    
11.4 
OnCore Safety Reporting  
In addition to protocol- and regulatory-required safety reporting, all serious adverse 
events (SAEs) will be captured in the Oncore system within 1 business day of 
notification.  Initial SAE reporting will include as much detail as available, with follow-up 
to provide complete information.   
Attributions will be assessed to study drugs, procedures, study disease, and other 
alternate etiology.      
11.5 
Study Accrual Oversight  
Accrual data will be entered into the IU Simon Cancer Center OnCore system. The 
Protocol Progress Committee (PPC) reviews study accrual twice per year while the PPC 
coordinator reviews accrual quarterly. 
11.6 
Protocol Deviation Reporting  
Protocol deviations will be entered into OnCore within 5 days of discovery and reviewed 
by the DSMC Chair on a monthly basis. Findings will be reported to the full DSMC at the 
time of study review.  For serious or repetitive protocol deviations, additional action may 
be required by the DSMC.   

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12 
ADVERSE EVENTS 
12.1 
Definitions of Adverse Events 
12.1.1 Adverse Event 
An adverse event (AE) is defined as any untoward medical occurrence associated with 
the use of a drug in humans, whether or not considered drug related. An adverse event 
can be any unfavorable and unintended sign (e.g. an abnormal laboratory finding), 
symptom, or disease temporarily associated with the use of a drug, without any 
judgment about causality.  Adverse events will be graded according to the NCI Common 
Toxicity Criteria, Version 4.0 (Appendix A). 
12.1.2 Serious Adverse Event (SAE) 
A serious adverse event is any untoward medical occurrence resulting in one or more of 
the following: 
• Results in death or ANY death occurring within 28 days of last dose of study drug 
(even if it is not felt to be drug related)  
• Is life-threatening (defined as an event in which the patient was at risk of death at 
the time of the event; it does not refer to an event which hypothetically might 
have caused death if it were more severe) 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
NOTE: Hospitalizations that are not considered SAEs are:  
o Hospitalization planned prior to first administration of study drug 
o Hospitalization for elective treatment of a pre-existing condition unrelated to 
the study medication 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly or birth defect 
• Is an important medical event (defined as a medical event(s) that may not be 
immediately life-threatening or result in death or hospitalization but, based upon 
appropriate medical and scientific judgment, may jeopardize the patient or may 
require intervention (e.g., medical, surgical) to prevent one of the other serious 
outcomes listed in the definition above).  Examples of such events include, but 
are not limited to, intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions not resulting in 
hospitalization; or the development of drug dependency or drug abuse. 

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12.1.3 Unexpected Adverse Event 
An adverse event not mentioned in the Investigator's Brochure or package insert or the 
specificity or severity of which is not consistent with the Investigator's brochure or 
package insert. 
12.1.4 Determining Attribution to the Investigational Agent(s) 
Attribution: An assessment of the relationship between the AE and the medical 
intervention. CTCAE does not define an AE as necessarily “caused by a therapeutic 
intervention”. After naming and grading the event, the clinical investigator must assign 
an attribution to the AE using the following attribution categories: 
Relationship 
Attribution 
Description 
Unrelated to 
investigational 
agent/intervention 
Unrelated 
The AE is clearly NOT 
related 
Unlikely 
The AE is doubtfully 
related 
Related to investigational 
agent/intervention 
Possible 
The AE may be related 
Probable 
The AE is likely related 
Definite 
The AE is clearly related 
12.2 
Adverse Event Reporting Requirements: 
Adverse events will be recorded for the first study drug administration and also for the 
prostate biopsy (if indicated) regardless of whether or not the event(s) are considered 
related to trial medications. All AEs considered related to trial medication will be 
followed until resolution, return to baseline, or deemed clinically insignificant, even if this 
occurs post-trial. 
12.2.1 Reporting to the IRB:  
Unanticipated problems involving risks to subjects or others will be reported promptly 
to the IRB if they:  
• unexpected; 
• related or possibly related to participation in the research; and 
• suggest that the research places subjects or others at a greater risk of harm 
than was previously known or recognized.   
If the serious adverse event does not meet all three (3) criteria listed above, the event 
does not have to be promptly reported to the IU IRB.  However, it should be reported at 
the time of continuing review. 

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Prompt reporting of unanticipated problems to the IRB is defined as within 5 days from 
becoming aware of the event. 
12.2.2 Reporting to the IUSCC Data Safety Monitoring Committee: 
Regardless of study sponsorship, the study team must enter all initial and follow-up 
SAE, expedited, and noncompliance reports into OnCore® for review by the DSMC chair 
and/or coordinator. Expedited reports may include IRB Prompt Report Forms, AdEERS 
reports, MedWatch, and additional SAE forms as required by the sponsor. When follow-
up information is received, a follow-up report should also be created in OnCore®. This 
DSMC reporting requirement is in addition to any other regulatory bodies to be notified 
(i.e. IRB, FDA, pharmaceutical company, etc.). The DSMC chair and/or coordinator will 
review all SAE, expedited, and noncompliance reports monthly. 
13 
 PATIENT CONSENT AND PEER JUDGEMENT 
The protocol and informed consent form for this study must be approved in writing by the 
appropriate IRB prior to any patient being registered on this study.   
Changes to the protocol, as well as a change of principal investigator, must also be 
approved by the Board.  Records of the Institutional Review Board review and approval 
of all documents pertaining to this study must be kept on file by the investigator and are 
subject to inspection at any time during the study.  Periodic status reports must be 
submitted to the Institutional Review Board at least yearly, as well as notification of 
completion of the study and a final report within 3 months of study completion or 
termination.   
The study will be conducted in compliance with ICH guidelines and with all applicable 
federal (including 21 CFR parts 56 & 50), state or local laws. 
14 
REFERENCES 
Afshar-Oromieh, A., Holland-Letz, T., Giesel, F. L., Kratochwil, C., Mier, W., Haufe, S., et al. 
(2017). Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with 
recurrent prostate cancer: evaluation in 1007 patients. European Journal of Nuclear 
Medicine and Molecular Imaging, 44(8), 1258–1268. http://doi.org/10.1007/s00259-017-
3711-7 
Bahler C., Cary C., Boris R., Tirkes T., Masterson T., Gardner T., Koch M. (2017). Is magnetic 
resonance imaging sensitive enough for partial gland high intensity focused ultrasound 
treatment? Comparing prostate cancer lesions between magnetic resonance imaging and 
prostatectomy specimens. The Journal of Urology, 197(4), e98. 

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Borofsky, S., George, A. K., Gaur, S., Bernardo, M., Greer, M. D., Mertan, F. V., et al. (2017). 
What Are We Missing? False-Negative Cancers at Multiparametric MR Imaging of the 
Prostate. Radiology, 152877–10.  
Eder, M., Neels, O., Müller, M., Bauder-Wüst, U., Remde, Y., Schäfer, M., et al. (2014). Novel 
Preclinical and Radiopharmaceutical Aspects of [68Ga]Ga-PSMA-HBED-CC: A New PET 
Tracer for Imaging of Prostate Cancer. Pharmaceuticals, 7(7), 779–796. 
http://doi.org/10.3390/ph7070779 
Eiber, M., Maurer, T., Souvatzoglou, M., Beer, A. J., Ruffani, A., Haller, B., et al. (2015). 
Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand PET/CT in 248 Patients with Biochemical 
Recurrence After Radical Prostatectomy. Journal of Nuclear Medicine : Official Publication, 
Society of Nuclear Medicine, 56(5), 668–674. http://doi.org/10.2967/jnumed.115.154153 
Eiber M, Weirich G, Holzapfel K, Souvatzoglou M, Haller B, Rauscher I, et al. Simultaneous 
68Ga-PSMA HBED-CC PET/ MRI improves the localization of primary prostate cancer. Eur 
Urol. 70:829–36; 2016.  
Green MA, Eitel JA, Fletcher JW, Mathias CJ, Tann MA, Gardner T, Koch MO, Territo W, 
Polson H, Hutchins GD. Estimation of radiation dosimetry for 68Ga-HBED-CC (PSMA-11) in 
patients with suspected recurrence of prostate cancer. Nucl Med Biol. 46:32-35; 2017.  doi: 
10.1016/j.nucmedbio.2016.11.002. PubMed PMID: 28012435. 
Jambor, I., Kuisma, A., Kähkönen, E., Kemppainen, J., Merisaari, H., Eskola, O., et al. (2017). 
Prospective evaluation of 18F-FACBC PET/CT and PET/MRI versus multiparametric MRI in 
intermediate- to high-risk prostate cancer patients (FLUCIPRO trial). European Journal of 
Nuclear Medicine and Molecular Imaging, 66(Suppl 1), 7. http://doi.org/10.1007/s00259-017-
3875-1 
Koerber, S. A., Utzinger, M. T., Kratochwil, C., Kesch, C., Haefner, M. F., Katayama, S., et al. 
(2017). 68Ga-PSMA-11 PET/CT in Newly Diagnosed Carcinoma of the Prostate: Correlation 
of Intraprostatic PSMA Uptake with Several Clinical Parameters. Journal of Nuclear Medicine 
: Official Publication, Society of Nuclear Medicine, 58(12), 1943–1948. 
Le, J. D., Tan, N., Shkolyar, E., Lu, D. Y., Kwan, L., Marks, L. S., et al. (2015). Multifocality and 
Prostate Cancer Detection by Multiparametric Magnetic Resonance Imaging: Correlation 
with Whole-mount Histopathology. European Urology, 67(3), 569–576.  
Musunuru, H. B., Yamamoto, T., Klotz, L., Ghanem, G., Mamedov, A., Sethukavalan, P., et al. 
(2016). Active Surveillance for Intermediate Risk Prostate Cancer: Survival Outcomes in the 
Sunnybrook Experience. The Journal of Urology, 196(6), 1651–1658. 
http://doi.org/10.1016/j.juro.2016.06.102 
Pokorny, M. R., de Rooij, M., Duncan, E., Schröder, F. H., Parkinson, R., Barentsz, J. O., & 
Thompson, L. C. (2014). Prospective study of diagnostic accuracy comparing prostate 
cancer detection by transrectal ultrasound-guided biopsy versus magnetic resonance (MR) 
imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. 
European Urology, 66(1), 22–29.  

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Sonn, G. A., Fan, R. E., Ghanouni, P., Wang, N. N., Brooks, J. D., Loening, A. M., et al. (2017). 
Prostate Magnetic Resonance Imaging Interpretation Varies Substantially Across 
Radiologists. European Urology Focus, 1–8. 
Womble, P. R., MONTIE, J. E., Ye, Z., Linsell, S. M., Lane, B. R., Miller, D. C., Michigan 
Urological Surgery Improvement Collaborative. (2015). Contemporary use of initial active 
surveillance among men in Michigan with low-risk prostate cancer. European Urology, 67(1), 
44–50.  
Wysock, J. S., Rosenkrantz, A. B., Huang, W. C., Stifelman, M. D., Lepor, H., Deng, F.-M., et al. 
(2014). A prospective, blinded comparison of magnetic resonance (MR) imaging-ultrasound 
fusion and visual estimation in the performance of MR-targeted prostate biopsy: the 
PROFUS trial. European Urology, 66(2), 343–351. 
http://doi.org/10.1016/j.eururo.2013.10.048 
Zlotta, A. R., Egawa, S., Pushkar, D., Govorov, A., Kimura, T., Kido, M., et al. (2013). 
Prevalence of prostate cancer on autopsy: cross-sectional study on unscreened Caucasian 
and Asian men. Journal of the National Cancer Institute, 105(14), 1050–1058. 
http://doi.org/10.1093/jnci/djt151 
 
 
 
 

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15 
APPENDICES 
15.1 
Appendix A 
NCI Common Toxicity Criteria (Version 4.0) 
Due to the size of the latest version of the Common Toxicity Criteria, copies of this 
appendix are not included with this protocol document. 
An electronic copy is available on the CTEP web site, 
http://ctep.cancer.gov/reporting/ctc.html 
 
 

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15.2 
Appendix B 
Performance Status Scales/Scores 
ECOG or Zubrod                               Karnofsky  
                ___Lansky__ 
 
       
Score        Activity               Score                Activity                      Score               Activity 
0 
Fully active, able 
to carry on all pre-
disease 
performance 
without restriction. 
100 
 
 
90 
Normal, no complaints, no 
evidence of disease. 
 
Able to carry on normal 
activity; minor signs or 
symptoms of disease. 
 
100 
 
 
90 
Fully active, normal. 
 
 
Minor restrictions in physically 
strenuous activity. 
1 
Restricted in 
physically 
strenuous activity 
but ambulatory 
and able to carry 
out work of a light 
or sedentary 
nature, e.g., light 
housework, office 
work. 
80 
 
 
 
 
70 
Normal activity with effort; 
some signs or symptoms of 
disease. 
 
Cares for self, unable to 
carry on normal activity or 
do active work. 
80 
 
 
 
 
70 
Active, but tires more quickly. 
 
 
 
Both greater restriction of and 
less time spent in play activity. 
2 
Ambulatory and 
capable of all 
selfcare but 
unable to carry out 
any work activities.  
Up and about 
more than 50% of 
waking hours. 
 
 
60 
 
 
 
50 
Requires occasional 
assistance, but is able to 
care for most of his/her 
needs. 
 
Requires considerable 
assistance and frequent 
medical care. 
 
 
60 
 
 
 
50 
Up and around, but minimal 
active play; keeps busy with 
quieter activities. 
 
 
Gets dressed, but lies around 
much of the day; no active play; 
able to participate in all quiet 
play and activities. 
3 
Capable of only 
limited selfcare, 
confined to bed or 
chair more than 
50% of waking 
hours. 
40 
 
 
 
30 
Disabled, requires special 
care and assistance. 
 
Severely disabled, 
hospitalization indicated.  
Death not imminent. 
40 
 
 
 
30 
Mostly in bed; participates in 
quiet activities. 
 
In bed; needs assistance even 
for quiet play. 

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4 
Completely 
disabled.  Cannot 
carry on any 
selfcare. Totally 
confined to bed or 
chair. 
20 
 
 
10 
Very sick, hospitalization 
indicated.  Death not 
imminent. 
Moribund, fatal processes 
progressing rapidly. 
20 
 
 
10 
 
Often sleeping; play entirely 
limited to very passive 
activities. 
No play; does not get out of 
bed. 
 
 

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15.3 
Appendix C 
Fusion Biopsy Procedure 
Concurrent acquisition of 68Ga-PSMA-11 PET data will be added to our present 
standard-of-care prostate mpMRI protocol performed in support of surgery planning or 
fusion biopsy for patients with prostate cancer.  There are commercially available 
devices which allow performing a biopsy by fusing the MR targeted lesion with the real-
time trans-rectal ultrasound image and thereby increasing the chance of prostate cancer 
detection. The fusion biopsy will be performed in the urology clinic, with at least two 
cores from each regions-of-interest defined by both mpMRI and PET.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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15.4 
Appendix D 
Sextant Based Analysis 
The biopsy plans will be re-assessed with full knowledge of all the mpMRI and PET 
findings, to define whether this combined data change diagnostic confidence and/or 
alter intended biopsy sites.  For the primary outcome, a “sextant” based analysis will be 
performed as previously described (Eiber et al 2016). The sextants are right-base, right-
mid, right-apex, left-base, left-mid, and left-apex.  Lesions <5 mm or Gleason 3+3 are 
generally not considered clinically relevant.   
 
 
 
 
 
 
 
Figure 4. Three different biopsies (A-C) will be performed on each patient during a 
single session.