Clinical trial NCT02919111
Conditions: Prostate Cancer
Sponsor: University of California, San Francisco
Start date: 2016-09-23; Completion date: 2019-12-31
Enrollment: 299 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The investigators are imaging patients with prostate cancer using a new PET imaging agent (Ga-68-PSMA-11) in order to evaluate it's ability to detection prostate cancer in patients with high risk disease prior to prostatectomy.

Detailed description:
Imaging and staging of prostate cancer is critical for surgical and treatment planning. Patients with suspected metastatic prostate cancer will be imaged using Gallium-68 labeled PSMA-11 in order to demonstrate its utility. The investigators plan to utilize this data to obtain further approvals of the Ga-68-PSMA-11 compound, so that this agent will become available for clinical imaging in prostate cancer patients. In the pre-prostatectomy population, the primary objective is to determine the sensitivity and specificity for detection on nodal metastasis.

This compound has been shown to be superior to choline based PET agents for the staging of prostate cancer, both Carbon-11 and Fluorine-18 compounds. But this compound was not patented and therefore no company or private entity will make the investment required to bring Ga-68-PSMA-11 to market. In the vacuum of availability, academic groups must take the lead in order to collect the necessary data for future FDA approval.

Arms: arm 1: PSMA PET imaging: Patients will receive Ga-68 labeled PSMA-11 PET and then undergo PET/CT or PET/MRI approximately 55-70 minutes later.
Interventions: intervention 1: Ga-68 labeled PSMA-11 PET
Intervention descriptions: intervention 1: Patients will be imaged using Ga-68 labeled PSMA-11 PET to determine if the presence of metastatic disease. Prostate Specific Membrane Antigen (PSMA) is a protein expressed on prostate cancer cells that can be imaged using small molecules that target this protocol.

Protocol documents:
Prot_SAP_000.pdf: 
Proprietary and Confidential 
The information in this document is considered privileged and confidential, and may not be disclosed to others except 
to the extent necessary to obtain Institutional Review Board approval and informed consent, or as required by 
Federal and State laws.  Persons to whom this information is disclosed should be informed that this information is 
privileged and confidential and that it should not be further disclosed. 
Gallium-68 PSMA-11 PET in intermediate to high-risk 
preprostatectomy patients  
Protocol Number:  CC #16559 
Study Drug:  Gallium-68 PSMA-11 
Version Number:  Version 1.1 
Version Date:  6/8/2018 
IND Number:  127621 
Principal Investigator (Sponsor-Investigator) 
Thomas Hope, MD 
University of California San Francisco 
 
 
Co-Investigators 
Dr. Rahul Aggarwal, MD 
Dr. Peter Carroll, MD 
Dr. Matthew Cooperberg, MD 
Dr. Michael Evans, PhD 
Dr. Felix Feng, MD 
Dr. Larry Fong, MD 
Dr. Terence Friedlander, MD 
Dr. Kirsten Greene, MD 
Dr. John Kurhanewicz, PhD 
Dr. Amy Lin, MD 
Dr. Hao Nguyen, MD 
Dr. Mack Roach, MD 
Dr. Eric Small, MD 
Dr. Li Zhang, PhD (Statistician) 
Clinical Research Coordinator 
 
 
 
 
 
NCT# 02919111


 
 
Protocol Signature Page 
Protocol No.: 16559 
Version Date: 6/8/2018 
1. I agree to follow this protocol version as approved by the UCSF Protocol Review Committee 
(PRC), Committee on Human Research (CHR), and Data Safety Monitoring Committee 
(DSMC).  
2. I will conduct the study in accordance with applicable CHR requirements, Federal 
regulations, and state and local laws to maintain the protection of the rights and welfare of 
study participants.  
3. I certify that I, and the study staff, have received the requisite training to conduct this 
research protocol.  
4. I have read and understand the information in the Investigators’ Brochure (or Manufacturer’s 
Brochure) regarding the risks and potential benefits. I agree to conduct the protocol in 
accordance with Good Clinical Practices (ICH-GCP), the applicable ethical principles, the 
Statement of Investigator (Form FDA 1572), and with local regulatory requirements. In 
accordance with the FDA Modernization Act, I will ensure the registration of the trial on the 
www.clinicaltrials.gov website.  
5. I agree to maintain adequate and accurate records in accordance with CHR policies, 
Federal, state and local laws and regulations. 
UCSF Principal Investigator / Study Chair 
           Thomas A. Hope 
 
 
Printed Name 
 
 
Signature 
 
Date 
 
 


 
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Abstract 
Title 
Gallium-68 PSMA-11 PET in patients with biochemical recurrence 
Patient 
population 
• 
Intermediate to high-risk disease (as determined by elevated PSA 
[PSA>10], T-stage [T2b or greater], Gleason score [Gleason score > 6] or 
other risk factors). 
Rationale for 
Study 
Gallium-68 PSMA-11 has been shown to have a higher sensitivity for the 
detection of metastatic prostate cancer compared to choline based imaging. 
Primary 
Objective 
• 
Sensitivity, specificity, positive and negative predictive value of PSMA PET 
for the detection of regional nodal metastases compared to pathology at 
radical prostatectomy on a per patient basis using nodal regional 
correlation.  
Secondary 
Objectives 
• 
Sensitivity, specificity, positive and negative predictive value of PSMA PET 
for the detection of extra-pelvic nodal metastases, visceral metastases and 
osseous metastases compared to biopsy and imaging follow-up. 
• 
Safety. 
Exploratory 
Endpoints 
• 
Sensitivity, specificity, negative and positive predictive value for detection 
of regional nodal metastases in comparison to cross sectional imaging 
performed contemporaneously with the PSMA-11 PET. 
• 
One year PSA progression free survival, comparing patients with and 
without pelvic nodal metastases. 
• 
Correlation between SUVmax from PSMA-11 PET and short axis diameter 
of nodal disease on cross sectional imaging correlate to presence of true 
pathology. 
• 
Incidence of osseous and distant metastatic lesions. 
Study Design 
This is a phase 2/3 multi-center open label study.  
Number of 
patients 
Total population of patients will be 300 patients across all institutions. 
• 
300 patients imaged at UCSF. 
Duration of 
Therapy 
The study will involve a single imaging study. 
Duration of 
Follow up 
The patients will be followed-up by phone one to three days after the study 
completion. 
Duration of 
study 
The study will reach completion three years from the time the study opens to 
accrual. 


 
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Study Drugs 
Gallium-68 labeled PSMA-11 (or HBED-CC PSMA, DFKZ-11 or the 
Heidelberg compound) 
Safety 
Assessments 
Patient vital signs will be taken immediately before and after the 
administration of the radiopharmaceutical.  The patients will also be asked to 
report adverse events. 
 
 
 


 
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List of Abbreviations 
AE 
adverse event 
CHR 
Committee on Human Research (UCSF IRB) 
CRC 
Clinical Research Coordinator 
CRF 
case report form 
CT 
computerized tomography 
CTCEA 
Common Terminology Criteria for Adverse Events 
DSMC 
Data and Safety Monitoring Committee 
DSMP 
Data and Safety Monitoring Plan 
ECOG 
Eastern Cooperative Oncology Group 
FDA 
Food and Drug Administration 
Ga-68 
Gallium 68 
HDFCCC 
Helen Diller Family Comprehensive Cancer Center 
ICH 
International Conference on Harmonization 
IND 
investigational new drug application 
IRB 
Institutional Review Board 
IV 
intravenous 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute 
PET 
PK 
Positron Emission Tomography 
pharmacokinetics 
PRC 
PSA 
PSMA 
Protocol Review Committee (UCSF) 
Prostate specific antigen 
Prostate specific membrane antigen 
SD 
standard deviation 
 
 


 
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Table of Contents 
Protocol Signature Page ............................................................................................................... 0 
Abstract 
1 
List of Abbreviations ...................................................................................................................... 3 
Table of Contents .......................................................................................................................... 4 
1 
Introduction .......................................................................................................................... 6 
1.1 
Overview ............................................................................................................... 6 
1.2 
Background ........................................................................................................... 6 
1.3 
Patient Population .................................................................................................. 7 
2 
Objectives of the Study ........................................................................................................ 7 
2.1 
Primary .................................................................................................................. 7 
2.2 
Secondary .............................................................................................................. 7 
2.3 
Exploratory ............................................................................................................ 7 
2.4 
Endpoints ............................................................................................................... 7 
2.4.1 
Primary Endpoints ............................................................................................. 7 
2.4.2 
Secondary endpoints .......................................................................................... 8 
2.4.3 
Exploratory Endpoints ....................................................................................... 8 
3 
Study Design ....................................................................................................................... 8 
3.1 
Characteristics ....................................................................................................... 8 
3.2 
Number of Subjects ............................................................................................... 8 
3.3 
Eligibility Criteria .................................................................................................. 8 
3.3.1 
Inclusion Criteria ............................................................................................... 8 
3.3.2 
Exclusion Criteria .............................................................................................. 8 
3.4 
Duration of Follow Up .......................................................................................... 9 
3.5 
Study Timeline ...................................................................................................... 9 
3.5.1 
Primary Completion .......................................................................................... 9 
3.5.2 
Study Completion .............................................................................................. 9 
4 
Study Drugs ......................................................................................................................... 9 
4.1 
Description, Supply and Storage of Investigational Drugs ................................... 9 
4.1.1 
Investigational Drug #1 ..................................................................................... 9 
5 
Treatment Plan .................................................................................................................... 9 
5.1 
Dosage and Administration ................................................................................... 9 
5.1.1 
Other Modality(ies) or Procedures .................................................................... 9 
5.2 
Monitoring and Toxicity Management ................................................................ 10 
6 
Study Procedures and Observations (Appendix 2 and 3) .................................................. 10 
6.1 
Schedule of Procedures and Observations .......................................................... 10 
6.1.2 
Treatment Period ............................................................................................. 10 
6.1.3 
Site level image interpretation ......................................................................... 11 
6.1.4 
Clinical follow-up ............................................................................................ 11 
6.1.5 
Post-treatment Follow Up Visits ..................................................................... 11 
6.2 
Prohibited Medications ........................................................................................ 12 
7 
Reporting and Documentation of Results .......................................................................... 12 
7.1 
Evaluation of Efficacy (or Activity) .................................................................... 12 
7.2 
Evaluation of Safety ............................................................................................ 12 
7.3 
Definitions of Adverse Events ............................................................................ 12 


 
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Table of Contents 
7.3.1 
Adverse Event.................................................................................................. 12 
7.3.2 
Adverse reaction .............................................................................................. 12 
7.4 
Recording of an Adverse Event ........................................................................... 13 
7.5 
Follow-up of Adverse Events .............................................................................. 14 
7.6 
Expedited Reporting ............................................................................................ 14 
8 
Statistical Considerations and Evaluation of Results ......................................................... 15 
8.1 
Study Endpoints .................................................................................................. 15 
8.1.1 
Randomization ................................................................................................. 15 
8.2 
Determination of Sample Size and Accrual Rate ................................................ 15 
8.2.1 
Sample Size and Power Estimate .................................................................... 15 
8.2.2 
Accrual estimates ............................................................................................. 16 
8.3 
Analyses Plans ..................................................................................................... 16 
8.3.1 
Analysis Population ......................................................................................... 16 
8.3.2 
Analysis of Primary Endpoint ......................................................................... 16 
8.3.3 
Analysis of Secondary Endpoints .................................................................... 18 
8.3.4 
Analysis of Exploratory Endpoints.................................................................. 20 
9 
Study Management ............................................................................................................ 21 
9.1 
Pre-study Documentation .................................................................................... 21 
9.2 
Institutional Review Board Approval .................................................................. 21 
9.3 
Informed Consent ................................................................................................ 21 
9.4 
Changes in the Protocol ....................................................................................... 21 
10 
Protection of Human Subjects ........................................................................................... 21 
10.1 
Protection of Privacy ........................................................................................... 21 
References 
23 
Appendices 
25 
Appendix 1 
Performance Status Criteria ............................................................................... 25 
Appendix 2 
Schedule of procedures ..................................................................................... 26 
Appendix 3 (flow chart) ............................................................................................................... 27 
List of Tables 
Table 1.1 
Schedule of Study Procedures and Assessments ............................................ 26 
 
 
 
 


 
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1 
Introduction 
1.1 
Overview 
Imaging and staging of prostate cancer is critical for surgical and treatment planning.  We aim to 
image patients with suspected metastatic prostate cancer using Gallium-68 labeled HBED-CC 
PSMA (68Ga-PSMA-11) in order to demonstrate its utility.   We plan to utilize this data to obtain 
further approvals of the 68Ga-PSMA-11compound, so that this agent will become available for 
clinical imaging in prostate cancer patients.   
This compound has been shown to be superior to choline based PET agents for the staging of 
prostate cancer, both Carbon-11 and Fluorine-18 compounds.  But this compound was not 
patented and therefore no company or private entity will make the investment required to bring 
68Ga-PSMA-11 to market.  In the vacuum of availability, academic groups must take the lead in 
order to collect the necessary data for future FDA approval.  
The rate of prostatectomy is increasing in high-risk prostate cancer patients (1), which means 
that there is an increasing unmeet need to detect regional and distant metastases prior to 
surgery.  There have been two published studies looking in intermediate to high-risk patients 
using 68Ga-PSMA-11 PET prior to prostatectomy, demonstrating a per patient sensitivity for 
nodal metastases of 64-66% (2,3), much improved compared to conventional imaging 
modalities.  We aim to study the ability of 68Ga-PSMA-11 to detect pelvic nodal disease in 
intermediate and high-risk preprostatectomy patients. 
1.2 
Background 
Prostate cancer is the most commonly diagnosed cancer and second leading cause of cancer 
death in American men (1).   Existing conventional imaging (CT, MRI and bone scans) has a 
low sensitivity in detecting local recurrence or metastatic disease (2).  The one exception being 
NaF PET/CT for the detection of osseous metastasis.  Due to this limitation, numerous 
approaches to stage patients have been evaluated. 
Choline imaging has been frequently used, as prostate cancer exhibits increase choline uptake 
that has been associated with the presence of choline kinase (3).  Choline uptake is increased 
in comparison to FDG in both androgen dependent and independent prostate cancer patients 
(4).  Choline has also been shown to be sensitive for the detection of recurrent tumor in patients 
with PSA (prostate specific antigen) values of less than 1.0 ng/ml (5).  There are two forms of 
choline that are used in imaging prostate cancer, C-11 and F-18 choline.  C-11 choline has a 
short half-life of 20 minutes, which limits its detection for metastatic disease but results in 
improved local detection due to decreased urinary activity at the time of imaging.  F-18 choline 
has significant urinary excretion that limits evaluation of the prostate but, but has been shown to 
have better detection rates for distant metastatic disease (6).  C-11 choline has limited 
sensitivity for osseous metastasis, possibly due to the decreased uptake time (7).  Additionally, 
the sensitivity of C-11 choline is limited in patients with PSA values < 1.0 ng/ml (8-10).  Although 
choline PET may be limited in sensitivity, it clearly delineates more lesions than cross section 
imaging or bone scan in patients with known disease (11).   In 2012, the Mayo Clinic obtained 
NDA (new drug application) approval from the FDA for the use of C-11 choline.   
A separate approach is to image the prostate specific membrane antigen (PSMA).  PSMA is 
expressed on the majority of prostate cancer cells, and so would be an ideal cell membrane 
protein to image.  The initial imaging approach to PSMA imaging target the intracellular domain 
using Indium-111-capromab (Prostascint), a murine monoclonal antibody (12,13).  Although 
there was early promise for the detection of nodal metastasis (14), the agent was never able to 
adequately visualize osseous metastasis (15).  Although combination with SPECT/CT does 
improve lesion detection (16).  One main limitation to In-111-capromab is that it takes a 
prolonged time to localize to the target tissue, which likely relates to both the size of the 
monoclonal antibody and the fact that agent targets the intracellular domain of the PSMA 


 
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protein. Additionally, Prostascint also recognizes an intracellular epitope so the antibody must 
cross the membrane to be effective. This likely only occurs in permeable dead or dying tumor 
cells.  
Because of the limitations of In-111 capromab, there has been continued effort to develop 
agents that target the extracellular domain of the PSMA protein. The Ga-68 labeled PSMA-11 
compound has become of particular interest because in the last year there have been two 
important articles. The first demonstrates that PSMA-11 has a higher sensitivity for the detection 
of disease than F-18 choline in a head-to-head intra-patient comparison that included 37 
patients (17).  The second paper looked at the sensitivity of PSMA-11 in the detection of 
metastatic lesions in patients with recurrent prostate cancer (18).  Their results demonstrated a 
detection rate of 50% for patients with a PSA less than 1 ng/ml, and detection rate above 85% 
for patients with a PSA greater than 2 ng/ml.  These detection rates are significantly higher than 
that reported by groups using choline (5). 
Because of the improved resolution and image quality with PET, ability to quantitate uptake, 
increased sensitivity compared to choline, we intend to evaluate the utility of 68Ga-PSMA-11 for 
the imaging of prostate cancer. We expect that the data from this study will support applications 
for clinical approval of this imaging agent, leading to wider availability within the United States. 
1.3 
Patient Population 
Patients with intermediate to high-risk prostate cancer planning to undergo prostatectomy.  
2 
Objectives of the Study 
2.1 
Primary 
• 
Sensitivity, specificity, positive and negative predictive value of PSMA PET for the 
detection of regional nodal metastases compared to pathology at radical prostatectomy 
on a per patient basis using nodal regional correlation. 
2.2 
Secondary 
• 
Sensitivity, specificity, positive and negative predictive value of PSMA PET for the 
detection of extra-pelvic nodal metastases, visceral metastases and osseous 
metastases compared to biopsy and imaging follow-up. 
• 
Safety, as characterized by CTCAE 4.03. 
2.3 
Exploratory 
• 
Sensitivity, specificity, negative and positive predictive value for detection of regional 
nodal metastases in comparison to cross sectional imaging performed 
contemporaneously with the PSMA-11 PET. 
• 
One year PSA progression free survival, comparing patients with and without pelvic 
nodal metastases. 
• 
Correlation between SUVmax from PSMA-11 PET and short axis diameter of nodal 
disease on cross sectional imaging correlate to presence of true pathology. 
• 
Incidence of osseous and distant metastatic lesions. 
2.4 
Endpoints 
2.4.1 Primary Endpoints 
• 
PSMA PET results for regional nodal disease. 
• 
Nodal histology results from prostatectomy. 


 
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2.4.2 Secondary endpoints 
• 
PSMA PET results for extra-pelvic disease. 
• 
Biopsy results and imaging follow-up results 
2.4.3 Exploratory Endpoints 
• 
Time to PSA progression 
• 
SUVmax of lesions. 
• 
Presence of osseous and distant metastasis.  
• 
Safety: blood pressure, heart rate, self reported adverse events 
3 
Study Design 
3.1 
Characteristics 
This is a prospective, multi-center, open-label study in patients with prostate cancer. Eligible 
participants will undergo baseline assessments at enrollment. Study participants will receive a 
one-time administration of Ga-68 PSMA-11 and undergo a PET/CT or PET/MRI imaging study.  
3.2 
Number of Subjects 
A total of 300 patients will be enrolled across all sites.  300 patients will be imaged at UCSF. 
3.3 
Eligibility Criteria 
Patients must have baseline evaluations performed prior to the administration of the 
radiopharmaceutical and must meet all inclusion and exclusion criteria.  In addition, the patient 
must be thoroughly informed about all aspects of the study, including the study visit schedule 
and required evaluations and all regulatory requirements for informed consent.  The written 
informed consent must be obtained from the patient prior to enrollment.  The following criteria 
apply to all patients enrolled onto the study: 
3.3.1 Inclusion Criteria 
1. Biopsy proven prostate adenocarcinoma. 
2. Planned prostatectomy with lymph node dissection. 
3. Intermediate to high-risk disease (as determined by elevated PSA [PSA>10], T-stage 
[T2b or greater], Gleason score [Gleason score > 6] or other risk factors). 
4. Karnofsky performance status of ≥50 (or ECOG/WHO equivalent). 
5. Age > 18. 
6. Ability to understand a written informed consent document, and the willingness to sign it. 
3.3.2 Exclusion Criteria 
1. Patients not capable of getting PET study due to weight, claustrophobia, or inability to 
lay still for the duration of the exam. 
2. Neoadjuvant chemotherapy or radiation therapy prior to prostatectomy. 
a. Including focal ablation techniques (HiFu). 


 
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3. Androgen deprivation therapy or other neoadjuvant treatments prior to PET imaging and 
surgery. 
4. Contraindication to furosemide administration including prior allergy or adverse reaction 
to furosemide or sulfa drugs.  (Note: This exclusion criteria can be removed if 
Furosemide is omitted as part of the PET imaging protocol if a second-generation scatter 
correction is available for the used PET device). 
3.4 
Duration of Follow Up 
Patients will be followed for one to three day after the administration of the radiopharmaceutical. 
3.5 
Study Timeline 
3.5.1 Primary Completion 
The study will reach primary completion 36 months from the time the study opens to accrual. 
3.5.2 Study Completion 
The study will reach study completion 48 months from the time the study opens to accrual. 
4 
Study Drugs 
4.1 
Description, Supply and Storage of Investigational Drugs 
4.1.1 Investigational Drug #1 
Ga-68 labeled PSMA-11 (or PSMA-HBED-CC) is a radiopharmaceutical that will be produced 
under cGMP. 
5 
Treatment Plan 
5.1 
Dosage and Administration 
The imaging agent (Ga-68 PSMA-11 or PSMA-HBED-CC) will be administered on an outpatient 
basis.  It will be administered a single time intravenously prior to the PET/CT imaging.  The 
injected dose will be 3 to 7 mCi of 68Ga-PSMA-11. 
5.1.1 Other Modality(ies) or Procedures 
5.1.1.1 PET imaging 
a) 68Ga-PSMA-11 PET preparation and injection: The injected dose will be 111-259 MBq 
(3-7 mCi) of 68Ga-PSMA-11 PET.  A dose of 20 mg of Furosemide is recommended to 
be injected together with, shortly before or after administration of the radiotracer in order 
to minimize PET scatter artifacts from excreted radiotracer accumulation in the kidney 
and urinary bladder that can occur with PSMA-11.  Oral hydration and voiding is 
recommended prior to the start of the scan.  Furosemide should not be administered in 
patients with medical contraindications to furosemide administration including allergies 
and adverse reactions including sulfa allergies.  (Note: Application of Furosemide can be 
omitted as part of the PET imaging protocol if a second-generation scatter correction 
algorithm is available for the PET scanner used in this protocol).    PET imaging will 
begin 50-100 minutes after injection.  
b) PET protocol: Scan coverage will extend from mid thigh to the base of the skull, starting 
from the mid-thighs to prevent urinary bladder radiotracer accumulation at the start of 
PET imaging.  Bed position scan time will be dependent on each sites scanner 
capabilities.  At a minimum, 3 minutes per bed position will be used.  In certain 


 
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circumstances, coverage may be extended to the toes.  Contrast may be administered if 
requested by the referring clinician and is decided site dependent. 
i) 
If the patient has not had a diagnostic CT or MRI within one month of the 68Ga-
PSMA-11 PET, then 68Ga-PSMA-11 PET study will be performed with a diagnostic 
CT or MRI. 
c) Safety monitoring: Vital signs will be assessed immediately before and after injection of 
68Ga-PSMA-11 (HR and supine BP).  Patients will be monitored for adverse events 
during injection and for two hours after radiotracer administration.   Additionally, patient’s 
vitals (HR and supine BP) will be checked at the completion of the imaging study prior to 
leaving the imaging center. 
d) Patient follow-up: Patients will be contacted by phone one to three working days after 
68Ga-PSMA-11 PET to assess for the development of delayed adverse events.  Patients 
will be seen in the clinic if there are any concerning study related adverse events 
requiring further evaluation.  
5.2 
Monitoring and Toxicity Management 
Each patient receiving Ga-68 PSMA-11 will be evaluable for safety.  The safety parameters 
include physical findings and spontaneous reports of adverse events reported to the investigator 
by patients. 
6 
Study Procedures and Observations (Appendix 2 and 3) 
6.1 
Schedule of Procedures and Observations 
Screening assessments must be performed within 30 days prior to the first dose of 
investigational product.  Any results falling outside of the reference ranges may be repeated at 
the discretion of the investigator.  Treatment or visit delays for public holidays or weather 
conditions do not constitute a protocol violation. 
A written, signed, informed consent form (ICF) and a Health Insurance Portability and 
Accountability Act (HIPAA) authorization must be obtained before any study-specific 
assessments are initiated.  A copy of the signed ICF will be given to the subject and a copy will 
be filed in the medical record.  The original will be kept on file with the study records.   
6.1.1.1 Screening Assessments  
The Screening procedures and assessments must be completed within 30 days of the day 1 
Visit.  
• 
Laboratory values: all patients must have a recent PSA (preferably within 30 days prior 
to the 68Ga-PSMA-11 PET) 
• 
Pathology: all patients must have histopathology/biopsy of the prostate with a 
documented Gleason score  
• 
Performance status: all patients must have their Karnofsky performance status (or 
ECOG/WHO equivalent) evaluated (Appendix 1). 
6.1.2 Treatment Period 
6.1.2.1 Study Procedures, Imaging Day 1 
• 
Vital signs 
• 
Evaluation of adverse events 


 
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6.1.3 Site level image interpretation 
PET images will initially be interpreted by a board certified nuclear medicine physician or a 
board certified radiologist experienced in reading PET at the time of the imaging study at the 
institution that the study is being performed. These interpretations will not be used for final 
evaluation. 
 
6.1.4 Clinical follow-up 
a) Prostatectomy: patients without evidence of PSMA-11 PET positive nodal or metastatic 
disease noted on imaging will undergo radical prostatectomy.  If a PSMA-11 PET 
positive regional pelvic node is noted, the urologist will be informed of the location of the 
suspicious node and the patient will undergo prostatectomy with nodal dissection. 
i) 
Patients with nodes seen on PSMA-11 PET without positive nodes on pathology, will 
be rescanned with CT or MRI to determine if the suspicious node was thought to be 
removed.  A PSMA-11 PET may be repeated as well at the discretion of the treating 
physician. 
b) If sites of PSMA PET positive osseous or distant metastatic lesions are noted, the 
urologist will be informed, and further evaluation including further imaging (bone scan, 
NaF PET, CT or MRI cross section imaging) or targeted biopsy will be performed in 
order to restage the patient prior to the decision regarding whether or not a 
prostatectomy will be performed as per the responsible surgeon and standard of clinical 
care. 
6.1.5 Post-treatment Follow Up Visits 
Patients will be followed for one to three days after enrollment, by phone.  The following 
procedure will be performed at 1-3 days: 
• 
 Evaluation of adverse events 


 
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6.2 
Prohibited Medications 
There are no prohibited medications. 
7 
Reporting and Documentation of Results 
7.1 
Evaluation of Efficacy (or Activity) 
7.1.1.1 Definitions 
Evaluable for toxicity 
All patients will be evaluable for toxicity from the time of Ga-68 PSMA-11. 
7.2 
Evaluation of Safety 
Analyses will be performed for all patients receiving Ga-68 PSMA-11.  The study will use the 
CTCAE v4.0 for reporting of adverse events. 
7.3 
Definitions of Adverse Events 
7.3.1 Adverse Event 
An adverse event (also known as an adverse experience) is defined as any untoward medical 
occurrence associated with the use of a drug in humans, whether or not considered drug 
related.  More specifically, an adverse event (can be any unfavorable and unintended sign (e.g., 
an abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
drug, without any judgment about causality.  An adverse event can arise from any use of the 
drug (e.g., off-label use, use in combination with another drug) and from any route of 
administration, formulation, or dose, including an overdose.  
7.3.2 Adverse reaction 
An adverse reaction is defined as any adverse event caused by the use of a drug.  Adverse 
reactions are a subset of all suspected adverse reactions for which there is reason to conclude 
that the drug caused the event. 
7.3.2.1 Suspected  
A suspected adverse reaction is defined as any adverse event for which there is a reasonable 
possibility that the drug caused the adverse event. For the purposes of IND safety reporting, 
“reasonable possibility” indicates that there is evidence to suggest a causal relationship 
between the drug and the adverse event.  A suspected adverse reaction implies a lesser degree 
of certainty about causality than an adverse reaction. 
7.3.2.2 Unexpected  
An adverse event or suspected adverse reaction is considered unexpected if it is not listed in 
the investigator brochure or package insert(s), or is not listed at the specificity or severity that 
has been observed, or, if an investigator brochure is not required or available, is not consistent 
with the risk information described in the general investigational plan or elsewhere in the current 
application.  
“Unexpected,” as used in this definition, also refers to adverse events or suspected adverse 
reactions that are mentioned in the investigator brochure as occurring with a class of drugs or 


 
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as anticipated from the pharmacological properties of the drug, but are not specifically 
mentioned as occurring with the particular drug under investigation. 
Adverse events that would be anticipated to occur as part of the disease process are 
considered unexpected for the purposes of reporting because they would not be listed in the 
investigator brochure.  For example, a certain number of non-acute deaths in a cancer trial 
would be anticipated as an outcome of the underlying disease, but such deaths would generally 
not be listed as a suspected adverse reaction in the investigator brochure. 
7.3.2.3 Serious 
An adverse event or suspected adverse reaction is considered serious if, in the view of either 
the investigator or sponsor, it results in any of the following outcomes:  
• 
Death 
• 
Life-threatening adverse event 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life function 
• 
Congenital anomaly/birth defect 
Important medical events that may not result in death, are life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, 
they may jeopardize the patient or subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition.  Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood 
dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
7.3.2.4 Life-threatening 
An adverse event or suspected adverse reaction is considered life-threatening if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject at immediate risk 
of death. It does not include an adverse event or suspected adverse reaction that, had it 
occurred in a more severe form, might have caused death.  
7.4 
Recording of an Adverse Event 
All grade 3 and above adverse events will be recorded using the NCI CTCAE v4.0.   The 
Investigator will assign attribution of the possible association of the event with use of the 
investigational drug.  
Relationship  
Attribution  
Description  
Unrelated to investigational 
drug/intervention 
Unrelated 
The AE is clearly NOT related to the 
intervention  
Unlikely 
The AE is doubtfully related to the 
intervention  
Related to investigational 
drug/intervention 
Possible 
The AE may be related to the intervention  
Probable 
The AE is likely related to the intervention  
Definite 
The AE is clearly related to the intervention  
 


 
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Signs or symptoms reported as adverse events will be graded and recorded by the Investigator 
according to the CTCAE.  When specific adverse events are not listed in the CTCAE they will be 
graded by the Investigator as none, mild, moderate or severe according to the following grades 
and definitions: 
Grade 0 
No AE (or within normal limits) 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
Grade 2 
Moderate; minimal, local, or noninvasive intervention (e.g., packing, cautery) 
indicated; limiting age-appropriate instrumental activities of daily living (ADL) 
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care ADL 
Grade 4: Life-threatening consequences; urgent intervention indicated 
Grade 5: Death related to AE 
7.5 
Follow-up of Adverse Events 
All adverse events will be followed with appropriate medical management until resolved.  
Patients removed from study for unacceptable adverse events will be followed until resolution or 
stabilization of the adverse event.  For selected adverse events for which administration of the 
investigational drug was stopped, a re-challenge of the subject with the investigational drug may 
be conducted if considered both safe and ethical by the Investigator. 
7.6 
Expedited Reporting  
Reporting to the Data and Safety Monitoring Committee 
If a death occurs during the treatment phase of the study or within 30 days after the last 
administration of the study drug(s) and it is determined to be related either to the study drug(s) 
or to a study procedure, the Investigator or his/her designee must notify the DSMC Chair (or 
qualified alternate) within 1 business day of knowledge of the event.  The contact may be by 
phone or e-mail. 
Reporting to UCSF Committee on Human Research (Institutional Review Board) 
The Principal Investigator must report events meeting the UCSF CHR definition of 
“Unanticipated Problem” (UP) and the San Francisco VA Medical Center within 5 business days 
of his/her awareness of the event.  
Expedited Reporting to the Food and Drug Administration 
If the study is being conducted under an IND, the Sponsor-Investigator is responsible for 
determining whether or not the suspected adverse reaction meets the criteria for expedited 
reporting in accordance with Federal Regulations (21 CFR §312.32).  
The Investigator must report in an IND safety report any suspected adverse reaction that is both 
serious and unexpected.  The Sponsor-Investigator needs to ensure that the event meets all 
three definitions:  
• 
Suspected adverse reaction (as defined in 6.1.30) 
• 
Unexpected (as defined in 0) 
• 
Serious (as defined in 6.1.5) 


 
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If the adverse event does not meet all three of the definitions, it should not be submitted as an 
expedited IND safety report. 
The timeline for submitting an IND safety report to FDA is no later than 15 calendar days after 
the Investigator determines that the suspected adverse reaction qualifies for reporting (21 CFR 
312.32(c)(1)).  
Any unexpected fatal or life-threatening suspected adverse reaction will be reported to FDA no 
later than 7 calendar days after the Investigator’s initial receipt of the information (21 CFR 
312.32(c)(2)).  
Any relevant additional information that pertains to a previously submitted IND safety report will 
be submitted to FDA as a Follow-up IND Safety Report without delay, as soon as the 
information is available (21 CFR 312.32(d)(2)).   
8 
Statistical Considerations and Evaluation of Results 
8.1 
Study Endpoints 
Primary endpoints:  
• 
PSMA PET results for regional nodal disease. 
• 
Nodal histology results from prostatectomy.   
8.1.1 Randomization 
There will be no randomization performed.  There will be no blinding performed. 
8.2 
Determination of Sample Size and Accrual Rate 
8.2.1 Sample Size and Power Estimate 
Across all sites, the estimated sample size will be 271 patients in total to adequately power the 
primary aim. Our power analysis will be based on the comparison of sensitivity between 
conventional imaging and PSMA PET.  With a power of 80% and a significance level of 0.01, we 
will require a sample size of 61 patients with nodal metastases.  Given the assumptions below 
we will need to enroll a total of 271, although only those undergoing prostatectomy will be 
included for analysis (203 patients). 
i) 
30% of intermediate to high-risk patients have nodal metastases at prostatectomy. 
ii) 25% of patients will not undergo the planned prostatectomy.  Patients that do not 
undergo prostatectomy will not be included in the analysis population, and will not 
undergo central imaging review. 
iii) Conventional imaging has a 45% detection sensitivity for nodal metastases on a per 
patient basis (2). 
iv) PSMA PET has a 65% detection sensitivity for nodal metastases on a per patient 
basis. 


 
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8.2.2 Accrual estimates 
At all sites, we anticipate enrolling 300 patients in total. 300 patients will be enrolled at UCSF. 
8.3 
Analyses Plans 
8.3.1 Analysis Population 
All patients that undergo prostatectomy and have histology correlates will be included in the 
analysis for the primary endpoint. 
8.3.2 Analysis of Primary Endpoint 
a) Imaging interpretation 68Ga-PSMA-11 PET: 
PET images will initially be interpreted by a board certified nuclear medicine physician or 
a board certified radiologist experienced in reading PET at the time of the imaging study 
at the institution that the study is being performed. These interpretations will not be used 
for final evaluation.  Imaging data will be anonymized and collected at a central site. PET 
data will be interpreted by three different readers in a random order at separate reading 
sessions.  Cross sectional imaging from the PET will be available for anatomic correlate.  
Final reads for each patient will be interpreted as positive or negative for the presence of 
pelvic nodal disease, and positive or negative for the presence of osseous metastatic 
disease and soft tissue metastases outside of the pelvis.  68Ga-PSMA PET reading 
training set and guides will be provided and completion of this training will be required for 
all central review readers.   
Visual interpretation of PET data:  
Regions of suspected disease will be graded on a two-point scale by each reader 
(0=Negative or 1=Positive). A region will be judged as positive if at least one lesion in 
this region is visually positive.  
i) 
Lymph nodes will be considered positive if the 68Ga-PSMA-11 uptake is focal and 
greater than adjacent background. Pelvic lymph nodes will be subclassified 
according to their localization as follows: R/L obturator, R/L external iliac, R/L internal 
iliac and other (total of 7 subgroups). 
ii) Visceral lesions will be considered positive if the 68Ga-PSMA-11 uptake is focal and 
greater than physiologic background activity of the involvement organ or anatomic 
site. 
iii) Bone lesions will be considered positive if the 68Ga-PSMA-11 uptake is focal and 
greater than physiologic bone marrow.  
b) Pathology analysis: Specimens from prostatectomy will be evaluated for the presence of 
nodal metastasis.  This will be reported on a per patient basis as positive or negative.   
i) 
Nodes will be marked by location per site specific protocol.  For example if the 
urologist removed left and right nodal regions separately, then that patient will have 
two nodal regions (left/right).  If a different surgeon removes nodes in six groups 
(bilateral internal/external/obturator nodes), then that patient will have six nodal 
regions that will be analyzed.  


 
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ii)  Although not routinely performed during standard practice, immunohistochemical 
staining for PSMA of tumor specimens (primary and lymph node metastases) may be 
performed, but is not required for this study. 
iii) The number of nodes counted on pathology will also be recorded. 
c) Analysis plan for Primary Aim 1: For this study to reach success, two out of the three 
readers will have to demonstrate a detection sensitivity of 65% or greater for nodal 
metastases.  Additionally, two out of the three readers will have to demonstrate a 
detection specificity of 90% or greater for regional nodal metastases based upon region 
as defined below on a per patient level.  The sensitivity, specificity, positive and negative 
predictive value of PSMA-11 PET for the detection on a per patient basis will be 
determined using the below criteria: 
i) 
True positive patient: 
(1) PSMA-11 PET positive for regional nodes; pathology at prostatectomy positive 
for regional nodes.  Region will be defined by the granularity used by the 
urologist at time of prostatectomy.  Sensitivity will be calculated at a patient level 
by region, meaning that one correct region would make a true positive on a 
patient level.  Only one node needs to correspond between imaging and 
pathology for a patient to be considered a true positive. 
(2) PSMA-11 PET positive for regional nodes, pathology negative for regional nodes, 
imaging after prostatectomy demonstrates node was not removed at surgery, 
and follow-up biopsy or imaging demonstrates presence of nodal disease. 
(a) Criteria for positive node on follow-up imaging: imaging within 3-12 months, 
the node decreases by more than 30% (for patients undergoing systemic 
treatment or focal therapy at this site) or increase by more than 20% in short 
axis diameter in the absence of treatment (with a minimum of 3 mm in 
change in size). 
ii)  True negative patient: 
(1) PSMA-11 PET negative for regional nodes; pathology at prostatectomy negative 
for regional nodes. 
iii) False positive patient: 
(1) PSMA-11 PET positive for regional nodes, pathology at prostatectomy is 
negative, and imaging after prostatectomy demonstrates that node is no longer 
present. 
(2) PSMA-11 PET positive for regional node, but pathology at prostatectomy is 
positive for node but in a different nodal region than that node seen on PSMA 
PET. 
iv) False negative patient: 
(1) PSMA-11 PET negative for regional nodes, but pathology at prostatectomy is 
positive. 
v) Non-evaluable:  


 
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(1) PSMA-11 PET positive for regional nodes, pathology negative for regional nodes, 
imaging after prostatectomy demonstrates node was not removed at surgery, 
and no definitive follow-up is available. 
(2) Patients with extrapelvic nodal metastases will not be included in this analysis if 
patients do not undergo prostatectomy. 
 
8.3.3 Analysis of Secondary Endpoints 
a) Analysis plan for Secondary Endpoint 1: We will report the sensitivity, specificity, positive 
and negative predictive value of PSMA PET over all imaged regions as well as broken 
down by the following regions: extra-pelvic nodal metastases, visceral metastases and 
osseous metastases.  Follow-up for extra-pelvic nodal metastases, visceral metastases 
and osseous metastases are defined as below: 
i) 
Lymph nodes will be assessed by change in size. 68Ga-PSMA-11 positive lymph 
nodes will be considered: 
(1) True positive:  
- If on follow-up imaging within 3-12 months, lymph nodes seen on CT or MRI 
decrease by more than 30% (for patients undergoing systemic treatment of focal 
therapy at this site) or increase by more than 20% in short axis diameter (with a 
minimum of 3 mm in change in size). 
- If patients with solitary lymph node regions show a decrease of PSA by greater 
than 50% after targeted treatment (i.e. external beam radiation) and the lymph 
nodes do not change in size (less than 30% decrease or less than 20% increase 
in short axis diameter). 
(2) False positive:  
- If on follow-up imaging within 3-12 months, sites of initial68Ga-PSMA-11 positive 
lymph node lesions seen on CT or MRI decrease by more than 30% without 
systemic therapy or focal therapy at this site. 
- If 68Ga-PSMA-11 positive lymph node lesions do not meet the criteria for above 
false positive or true positive findings. 
ii) Visceral lesions (non-lymph node soft tissue or organ) will be assessed by change in 
size. 68Ga-PSMA-11 positive visceral lesions will be considered: 
(1) True positive:  
- If on follow-up imaging within 3-12 months, visceral lesions seen on CT or MRI 
decrease by 30% (for patients undergoing systemic treatment of focal therapy at 
this site) or increase by 20% in largest diameter. 
- If patients with solitary visceral metastasis show a decrease of PSA by greater 
than 50% after targeted treatment (i.e. external beam radiation) and lesions do 
not change in size (less than 30% decrease or 20% increase in largest diameter). 
(2) False positive:  


 
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- If on follow-up imaging within 3-12 months, sites of initial68Ga-PSMA-11 positive 
visceral lesions seen on CT or MRI decrease by more than 30% without systemic 
therapy or focal therapy at this site. 
- If 68Ga-PSMA-11 positive visceral lesions do not meet the criteria for above 
false positive or true positive findings. 
iii) 68Ga-PSMA-11 positive bone lesions will be considered: 
(1) True positive: 
- If there was a corresponding positive sclerotic lesion on the CT portion of the 
68Ga-PSMA-11 PET in the same location as the PSMA uptake. 
- If there is focal uptake seen in the same location as the PSMA uptake on the 
baseline bone scan performed within one month of 68Ga-PSMA-11 PET. 
- If there is a lesion noted in the same location as the PSMA uptake on the initial 
MRI performed within one month of 68Ga-PSMA-11 PET. 
- If within 12 months follow-up CT demonstrates development of sclerosis in the 
same location as the PSMA uptake. 
- If within 12 months follow-up MRI demonstrates a new bone lesion in the same 
location as the PSMA uptake. 
- If within 12 months follow-up bone scan demonstrates new focal uptake in the 
same location as the PSMA uptake. 
(2) False positive: 
- If 68Ga-PSMA-11 positive bone lesions do not meet the criteria for true positive 
findings. 
iv) Histopathology correlation: for lesions that have biopsy correlation, we will use the 
following criteria to determine positive and negative lesions: 
(1) Positive HP/Biopsy: Confirmed sites of metastatic or tumor involvement by 
histopathology/biopsy will be discussed with the responsible physician/surgeon.   
(2) Negative Biopsy: Patients with suspected tumor recurrence on 68Ga-PSMA-11 
PET with negative histopathology/biopsy will be handled as outlined below: 
(a) Lymph nodes: 
− 
For patients undergoing nodal dissection: Patients will be rescanned with 
dedicated CT or MRI to determine if the suspicious 68Ga-PSMA-11 
positive node was removed.   
- If 68Ga-PSMA-11 positive lymph node is still present, a repeat biopsy 
can be pursued if clinically feasible and applicable, or follow-up using 
imaging as described above will be performed.    
- If the corresponding node was removed, then this will be considered a 
False Positive. 


 
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− 
For patients undergoing needle biopsy: Images of the procedure will be 
reviewed to determine if the correct node was biopsied.   
- If the correct node was biopsied, then a negative biopsy will be 
considered a False Positive. 
- If the incorrect node was biopsied, then follow-up imaging as described 
above will be performed. 
(b) Bone lesions:  Given the high rate of false negative biopsies for osseous 
metastases in patients with prostate cancer, patients with negative bone 
biopsies of PSMA PET positive lesions will be further evaluated: 
− 
If pathology demonstrates an alternative diagnoses that is known to be 
PSMA positive (eg Renal Cell Carcinoma metastases, Paget’s disease), 
then this will be considered a False Positive. 
− 
If pathology is indeterminate, then follow-up imaging as described above 
will be performed to determine if the lesion is a True Positive or False 
Positive. 
(c) Additionally a repeat 68Ga-PSMA-11 can also be obtained, as allowable, in 
addition to repeat conventional imaging (CT and/or MRI) in cases of negative 
biopsy to determine if the biopsy was true negative or false negative. 
b) Safety: Safety will be reported descriptively as rates of patient reported adverse events. 
Additionally, adverse events will be characterized and quantified by CTCAE 4.03. 
 
8.3.4 Analysis of Exploratory Endpoints 
PPVs on a per-patient and per-region-basis of 68Ga-PSMA-11 PET for detection of tumor 
location confirmed by histopathology/biopsy and conventional imaging follow-up will be 
calculated and reported along with the corresponding two-sided 95% confidence intervals. The 
paired McNemar’s test will be used to compare the PPVs of 68Ga-PSMA-11 PET imaging to the 
PPVs of conventional imaging. 
Sensitivity, specificity, and NPVs on a per-patient basis of 68Ga-PSMA-11 PET for detection of 
tumor location confirmed by histopathology/biopsy will be summarized in tabular format. 
Furthermore, the positive and negative likelihood ratios (LR+ and LR-) will be calculated and 
reported. Ninety-five confidence intervals of sensitivity, specificity, and NPV will be calculated 
using the Wilson score method. The comparisons of sensitivity, specificity, and NPV on a per-
patient basis of 68Ga-PSMA-11 PET imaging will be compared to of sensitivity, specificity, and 
NPV on a per-patient basis of conventional imaging using a paired McNemar’s test. 
Detection rates on a per-patient basis of 68Ga-PSMA-11 PET stratified by PSA value (0.2 - <0.5, 
0.5 - <1.0, 1.0 - <2.0, 2.0 - <5.0, 5.0) will be summarized in tabular format and compared 
between PSA strata using chi-square analysis. The impact of 68Ga-PSMA-11 PET on clinical 
management in BCR patients will be evaluated using descriptive statistics.  


 
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9 
Study Management 
9.1 
Pre-study Documentation 
This study will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki as stated in 21 CFR §312.120(c)(4); consistent with GCP and all 
applicable regulatory requirements. 
Before initiating this trial, the Investigator will have written and dated approval from the 
Institutional Review Board for the protocol, written informed consent form, subject recruitment 
materials, and any other written information to be provided to subjects before any protocol 
related procedures are performed on any subjects.   
The clinical investigation will not begin until either FDA has determined that the study under the 
Investigational Drug Application (IND) is allowed to proceed or the Investigator has received a 
letter from FDA stating that the study is exempt from IND requirements. 
9.2 
Institutional Review Board Approval 
The protocol, the proposed informed consent form, and all forms of participant information 
related to the study (e.g. advertisements used to recruit participants) will be reviewed and 
approved by the UCSF CHR (UCSF Institutional Review Board).  Prior to obtaining CHR 
approval, the protocol must be approved by the Helen Diller Family Comprehensive Cancer 
Center Site Committee and by the Protocol Review Committee (PRC).  The initial protocol and 
all protocol amendments must be approved by the IRB prior to implementation.   
9.3 
Informed Consent 
All participants must be provided a consent form describing the study with sufficient information 
for each participant to make an informed decision regarding their participation.  Participants 
must sign the CHR-approved informed consent form prior to participation in any study specific 
procedure.  The participant must receive a copy of the signed and dated consent document.  
The original signed copy of the consent document must be retained in the medical record or 
research file.  
9.4 
Changes in the Protocol 
Once the protocol has been approved by the UCSF CHR, any changes to the protocol must be 
documented in the form of an amendment.  The amendment must be signed by the Investigator 
and approved by PRC and the CHR prior to implementation.   
If it becomes necessary to alter the protocol to eliminate an immediate hazard to patients, an 
amendment may be implemented prior to CHR approval.  In this circumstance, however, the 
Investigator must then notify the CHR in writing within five (5) working days after 
implementation.  The Study Chair and the UCSF study team will be responsible for updating any 
participating sites. 
10 
Protection of Human Subjects 
10.1 Protection of Privacy 
Patients will be informed of the extent to which their confidential health information generated 
from this study may be used for research purposes. Following this discussion, they will be asked 
to sign the HIPAA form and informed consent documents. The original signed document will 


 
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become part of the patient’s medical records, and each patient will receive a copy of the signed 
document. The use and disclosure of protected health information will be limited to the 
individuals described in the informed consent document. 


 
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References 
1. 
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Oyen RH, Van Poppel HP, Ameye FE, Van de Voorde WA, Baert AL, Baert LV. Lymph 
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3. 
Contractor K, Challapalli A, Barwick T, et al. Use of [11C]choline PET-CT as a 
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Castellucci P, Ceci F, Graziani T, et al. Early biochemical relapse after radical 
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9. 
Castellucci P, Fuccio C, Rubello D, et al. Is there a role for ¹¹C-choline PET/CT in the 
early detection of metastatic disease in surgically treated prostate cancer patients with a 
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Giovacchini G, Picchio M, Scattoni V, et al. PSA doubling time for prediction of 
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radical prostatectomy. Eur J Nucl Med Mol Imaging. 2010;37:1106–1116. 
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Fuccio C, Castellucci P, Schiavina R, et al. Role of 11C-choline PET/CT in the restaging 
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Seltzer MA, Barbaric Z, Belldegrun A, et al. Comparison of helical computerized 
tomography, positron emission tomography and monoclonal antibody scans for 


 
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evaluation of lymph node metastases in patients with prostate specific antigen relapse 
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Kahn D, Williams RD, Manyak MJ, et al. 111Indium-capromab pendetide in the 
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Manyak MJ, Hinkle GH, Olsen JO, et al. Immunoscintigraphy with indium-111-capromab 
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Raj GV, Partin AW, Polascik TJ. Clinical utility of indium 111-capromab pendetide 
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Aparici CM, Carlson D, Nguyen N, Hawkins RA, Seo Y. Combined SPECT and 
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Afshar-Oromieh A, Zechmann CM, Malcher A, et al. Comparison of PET imaging with a 
(68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of 
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Eiber M, Maurer T, Souvatzoglou M, et al. Evaluation of Hybrid ⁶⁸Ga-PSMA Ligand 
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Ceci F, Uprimny C, Nilica B, et al. (68)Ga-PSMA PET/CT for restaging recurrent prostate 
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van Leeuwen PJ, Stricker P, Hruby G, et al. (68) Ga-PSMA has a high detection rate of 
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Appendices 
Appendix 1 Performance Status Criteria 
ECOG Performance Status Scale 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity 
Fully active, able to carry on all 
pre-disease performance without 
restriction 
100 
Normal, no complaints, no evidence 
of disease 
90 
Able to carry on normal activity; 
minor signs or symptoms of disease 
1 
Symptoms, but ambulatory 
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 
Normal activity with effort; some 
signs or symptoms of disease 
70 
Cares for self, unable to carry on 
normal activity or to do active work 
2 
In bed < 50% of the time 
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities 
Up and about more than 50% of 
waking hours 
60 
Requires occasional assistance, but 
is able to care for most of his/her 
needs 
50 
Requires considerable assistance 
and frequent medical care 
3 
In bed > 50% of the time 
Capable of only limited self-care, 
confined to bed or chair more 
than 50% of waking hours 
40 
Disabled, requires special care and 
assistance 
30 
Severely disabled, hospitalization 
indicated 
Death not imminent 
4 
100% bedridden 
Completely disabled 
Cannot carry on any self-care 
Totally confined to bed or chair 
20 
Very sick, hospitalization indicated 
Death not imminent 
10 
Moribund, fatal processes 
progressing rapidly 
5 
Dead 
0 
Dead 
 
 
 
 


 
Version date: 2018.06.08 
Protocol CC#: 16559  
Phase III – 68Ga-PSMA-11 Preprostatectomy 
 
Page 26 of 29 
Appendix 2 Schedule of procedures 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 1.1 
Schedule of Study Procedures and Assessments 
Period/ 
Procedure 
Screening 
Imaging day 1 
One day post imaging 
Study Day/Visit Day 
-30 to 1 
1 
2-4 
Informed consent 
X 
 
 
Laboratory values, history from 
medical record 
X 
 
 
Pre-survey 
X 
 
 
Performance status 
X 
 
 
Blood Pressure, HR 
X 
X 
 
Imaging Procedure 
Ga-68 PSMA-11 
 
X 
 
PET/CT or PET/MRI  
 
X 
 
Follow-up 
Adverse event reporting 
 
 
X 


 
Version date: 2018.06.08 
Protocol CC#: 16559  
Phase III – 68Ga-PSMA-11 Preprostatectomy 
 
Page 27 of 29 
Appendix 3 (flow chart) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PCa preprostatectomy protocol entry criteria: 
(1) Biopsy proven prostate adenocarcinoma. 
(2) Planned prostatectomy with lymph node dissection. 
(3) Intermediate to high-risk disease  
PSMA PET imaging study: 
Determine location of metastases: 
1. No extraprostatic disease. 
2. Pelvic only disease (to aortic bifurcation). 
3. Extrapelvic nodal disease. 
4. Osseous metastases. 
No extraprostatic 
disease: 
Perform prostatectomy 
with nodal dissection  
Osseous metastases: 
Biopsy or imaging follow-up  
Extrapelvic nodes: 
Biopsy or imaging follow-up  
Path negative: 
Repeat cross 
sectional imaging 
or PSMA-11 PET 
to demonstrate 
node removed  
Path positive: 
PSA follow-up x 1 
year  
Follow-up: 
PSA follow-up x 1 
year  
Pelvic only disease: 
Prostatectomy, LND with 
targeting of PSMA 
positive node.  
Path positive: 
PSA follow-up x 1 
year  

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