Clinical trial NCT03803475
Conditions: Prostate Cancer
Sponsor: Thomas Hope
Start date: 2018-10-11; Completion date: 2020-08-25
Enrollment: 485 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The investigators are imaging patients with prostate cancer using a new Positron Emission Tomography (PET) imaging agent (Ga-68-PSMA-11) in order to evaluate its ability to detect prostate cancer.

Detailed description:
Patients will be imaged using Ga-68 labeled PSMA-11 PET to determine if there is 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. PET imaging will begin 50-100 minutes after injection, but may be possible in certain circumstances for imaging to be delayed due to patient workflow or equipment issues

Primary Objective:

Sensitivity on a per-patient and per-region-basis (Table 1) of 68Ga-PSMA-11 PET for detection of tumor location confirmed by histopathology/biopsy, clinical and conventional imaging follow-up.

Arms: arm 1: 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 imaging. The injected dose will be 3 to 7 millicurie (mCi) +/- 10% of 68Ga-PSMA-11.
Interventions: intervention 1: Ga-68 labeled PSMA-11 intervention 2: Positron emission tomography-computed tomography (PET/CT) intervention 3: Positron emission tomography-magnetic resonance imaging (PET/MRI)
Intervention descriptions: intervention 1: Patients will be imaged using Ga-68 labeled PSMA-11 PET to determine if there is 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. intervention 2: Positron emission tomography-computed tomography (PET/CT) is a nuclear medicine technique which combines, in a single gantry, a positron emission tomography (PET) scanner and an x-ray computed tomography (CT) scanner, to acquire sequential images from both devices in the same session intervention 3: A PET/MRI scan is a two-in-one test that combines images from a positron emission tomography (PET) scan and a magnetic resonance imaging (MRI) scan in a single session

Protocol documents:
Prot_SAP_000.pdf: 
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Gallium-68 PSMA-11 PET in prostate cancer patients
Study Drug:  Gallium-68 PSMA-11
Version: 1.3
Version Date:  November 26, 2019
Principal Investigator (Sponsor-Investigator)
Thomas Hope, MD
University of California San Francisco
Revision History
Version 1.0
10/06/2018
Version 1.1
03/04/2019
Version 1.2
04/02/2019
NCT#  03803475


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Protocol Signature Page
Protocol No.: 185513
Version Date: 26NOV2019
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
Printed Name
Signature
Date


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Abstract
Title
Gallium-68 PSMA-11 PET in prostate cancer patients
Patient 
population
Patients with biopsy proven prostate cancer who have a concern for 
metastatic disease.
Rationale for 
Study
Gallium-68 PSMA-11 has been shown to have a higher sensitivity for the 
detection of metastatic prostate cancer than conventional imaging.
Primary 
Objective
Determine detection rate of PSMA-11 PET broken down by PSA 
Study Design
This is a single center open label study. 
Number of 
patients
Total population of patients will be 1,000 patients.
Duration of 
Therapy
The study will involve a single imaging study.
Duration of 
Follow up
No follow-up will be performed.
Duration of 
study
The study will reach completion two years from the time the study opens to 
accrual.
Study Drugs
Gallium-68 labeled PSMA-11 (PSMA-HBED-CC)
Safety 
Assessments
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..........................................................................................................2
Abstract ..................................................................................................................................3
List of Abbreviations................................................................................................................4
1
Introduction.....................................................................................................................7
1.1
Overview..............................................................................................................................7
1.2
Background..........................................................................................................................7
1.3
Previous experience with PSMA-11 ......................................................................................8
2
Objectives of the Study ....................................................................................................8
2.1
Primary ................................................................................................................................8
3
Study Design....................................................................................................................8
3.1
Characteristics......................................................................................................................8
3.2
Number of Subjects..............................................................................................................9
3.3
Eligibility Criteria..................................................................................................................9
3.3.1
Inclusion Criteria....................................................................................................................................9
3.3.2
Exclusion Criteria ...................................................................................................................................9
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 ...................................................................................................................10
4.1
Description, Supply and Storage of Investigational Drugs ...................................................10
4.1.1
Investigational Drug #1........................................................................................................................10
5
Treatment Plan..............................................................................................................10
5.1
Dosage and Administration ................................................................................................10
5.1.1
Other Modality(ies) or Procedures......................................................................................................10
5.2
Monitoring and Toxicity Management................................................................................11
6
Study Procedures and Observations ...............................................................................11
6.1
Schedule of Procedures and Observations..........................................................................11
6.1.1
Screening Assessments........................................................................................................................11
6.1.2
Treatment Period.................................................................................................................................11
6.2
Prohibited Medications......................................................................................................12
7
Reporting and Documentation of Results.......................................................................12


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7.1
Evaluation of Side Effects ...................................................................................................12
7.2
Evaluation of Safety ...........................................................................................................12
7.3
Definitions of Adverse Events.............................................................................................12
7.3.1
Adverse Event......................................................................................................................................12
7.3.2
Adverse Reaction.................................................................................................................................12
7.4
Recording of an Adverse Event...........................................................................................14
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.....................................................................................................................................16
8.2
Determination of Sample Size and Accrual Rate .................................................................16
8.2.1
Sample Size and Power Estimate.........................................................................................................16
8.2.2
Accrual estimates ................................................................................................................................16
8.3
Analyses Plans....................................................................................................................16
8.3.1
Analysis of Primary Endpoints .............................................................................................................16
9
Study Management .......................................................................................................16
9.1
Pre-study Documentation ..................................................................................................16
9.2
Institutional Review Board Approval ..................................................................................16
9.3
Informed Consent ..............................................................................................................17
9.4
Changes in the Protocol......................................................................................................17
10
Protection of Human Subjects ....................................................................................17
10.1
Protection of Privacy ..........................................................................................................17
References.............................................................................................................................18
Appendices............................................................................................................................20
Appendix 1
Schedule of Study Procedures and Assessments ..............................................20


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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 (more commonly called 68Ga-PSMA-11) in order to demonstrate its utility.   We plan to 
utilize this data to obtain further approvals of the 68Ga-PSMA-11 compound, 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 
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.  This protocol was developed in 
collaboration with the Clinical Trials Network of the Society of Nuclear Medicine and Molecular 
Imaging.  The inclusion criteria and study endpoints have been aligned so that inter-institutional 
sharing of data can be performed in order to pool data for final NDA submission.
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 


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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 
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 Ga-68 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
Previous experience with PSMA-11
We have completed numerous trials evaluating 68Ga-PSMA-11 at UCSF and in conjuction with 
other institutions.  These studies are currently being developed into an NDA application for 
submission to the FDA.
2
Objectives of the Study
2.1
Primary

Sensitivity on a per-patient and per-region-basis (Table 1) of 68Ga-PSMA-11 PET for
detection of tumor location confirmed by histopathology/biopsy, clinical and conventional
imaging follow-up.
3
Study Design
3.1
Characteristics
This is a prospective, single 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.


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3.2
Number of Subjects
It is anticipated that 1,000 patients will be enrolled in this study. 
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.
Male, age ≥ 18.
2.
Histopathologically proven prostate adenocarcinoma.
3.
Concern for metastatic disease in one of the following settings:
a.
Initial staging with intermediate to high risk prostate cancer.
b.
Biochemical recurrence after initial therapy.
4.
Ability to understand a written informed consent document, and the willingness to sign it.
3.3.2 Exclusion Criteria
1.
Patient unlikely to comply with study procedures, restrictions and requirements and 
judged by the Investigator to be unsuitable for study participation.
3.4
Duration of Follow Up
There will be no follow-up as part of this protocol.
3.5
Study Timeline
3.5.1 Primary Completion
The study will reach primary completion 24 months from the time the study opens to accrual.
3.5.2 Study Completion
The study will reach study completion 24 months from the time the study opens to accrual.


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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 imaging.  The injected 
dose will be 3 to 7 mCi  10% 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 intravenously injected dose will be 111-259 MBq (3-7 mCi  10%) of 68Ga-PSMA-11
PET.  A dose of 20 mg of furosemide (Lasix) is recommended to be injected i.v. 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 the gallium-68 radionuclide.  Oral hydration is recommended on the
day of the scan. Voiding is recommended immediately before 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,
but may be possible in certain circumstances for imaging to be delayed due to patient
workflow or equipment issues.  Scan time per bed position will be determined based on
each sites PET scanner capabilities.
b) Patient preparation: no fasting is required.
c)
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.  
5.2
Monitoring and Toxicity Management
Each patient receiving Ga-68 PSMA-11 will be evaluable for safety.  The safety parameters 
include spontaneous reports of adverse events reported to the investigator by patients.
6
Study Procedures and Observations
6.1
Schedule of Procedures and Observations
Screening assessments must be performed within 90 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.  
Data collected from the study visits will be stored in a study-specific Research Electronic Data 
Capture (REDCap) system.
6.1.1
Screening Assessments 
The screening procedures and assessments must be completed within 90 days of the Day 1 
Visit. 
1.
PSA.
o
A clinically drawn PSA that was performed prior to the patient signing the ICF,
but was performed within the screening window, may be used as the Screening
PSA.
6.1.2
Treatment Period
6.1.2.1 Study Procedures, Imaging Day 1

68Ga-PSMA-11 administration

PET imaging using either PET/CT or PET/MRI

Administration of intravenous contrast (for MRI or CT as clinically indicated)

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 Side Effects
7.1.1.1 Definitions
Evaluable for toxicity
All patients will be evaluable for toxicity from the time of 68Ga-PSMA-11.
7.2
Evaluation of Safety
Analyses will be performed for all patients receiving 68Ga-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.


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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 
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. 


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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
The AE is clearly NOT related to the 
intervention 
Unrelated to investigational 
drug/intervention
Unlikely
The AE is doubtfully related to the 
intervention 
Possible
The AE may be related to the intervention 
Probable
The AE is likely related to the intervention 
Related to investigational 
drug/intervention
Definite
The AE is clearly related to the intervention 
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 


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qualified alternate) within 1 business day of knowledge of the event.  The contact may be by 
phone or e-mail.
Data and Safety Monitoring Committee Contacts
DSMC Chair: 
DSMC Monitors 
Phone: 
Email:
Address: 
UCSF, Box 1705
San Francisco, CA 94158
Box 0128
UCSF Helen Diller Family 
Comprehensive Cancer Center
San Francisco, CA 94143
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)
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
Detection rate stratified by PSA level.


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8.1.1 Randomization
There will be no randomization performed.  
8.2
Determination of Sample Size and Accrual Rate
8.2.1 Sample Size and Power Estimate
1,000 patients will be enrolled as part of this study over two years.
8.2.2 Accrual estimates
We estimate that roughly 500 patients with prostate cancer will be enrolled in this trial per year. 
Over a two-year period, this will result in up to 1000 patients being enrolled in the study.
8.3
Analyses Plans
8.3.1 Analysis of Primary Endpoints
Based on local reads for the detection of metastatic disease, the rate of localization abnormal 
focus of radiotracer will be stratified based upon the PSA prior to imaging.
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.  


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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 
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
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Edwards BK, Noone A-M, Mariotto AB, et al. Annual Report to the Nation on the status of 
cancer, 1975-2010, featuring prevalence of comorbidity and impact on survival among 
persons with lung, colorectal, breast, or prostate cancer. Cancer. 2014;120:1290–1314.
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Oyen RH, Van Poppel HP, Ameye FE, Van de Voorde WA, Baert AL, Baert LV. Lymph 
node staging of localized prostatic carcinoma with CT and CT-guided fine-needle 
aspiration biopsy: prospective study of 285 patients. 1994;190:315–322.
3.
Contractor K, Challapalli A, Barwick T, et al. Use of [11C]choline PET-CT as a 
noninvasive method for detecting pelvic lymph node status from prostate cancer and 
relationship with choline kinase expression. Clin Cancer Res. 2011;17:7673–7683.
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of [18 F]fluorocholine and [18 F]fluorodeoxyglucose for positron emission tomography of 
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Castellucci P, Ceci F, Graziani T, et al. Early biochemical relapse after radical 
prostatectomy: which prostate cancer patients may benefit from a restaging 11C-Choline 
PET/CT scan before salvage radiation therapy? J Nucl Med. 2014;55:1424–1429.
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Brogsitter C, Zöphel K, Kotzerke J. 18F-Choline, 11C-choline and 11C-acetate PET/CT: 
comparative analysis for imaging prostate cancer patients. Eur J Nucl Med Mol Imaging. 
2013;40 Suppl 1:S18–S27.
7.
Picchio M, Spinapolice EG, Fallanca F, et al. [11C]Choline PET/CT detection of bone 
metastases in patients with PSA progression after primary treatment for prostate cancer: 
comparison with bone scintigraphy. Eur J Nucl Med Mol Imaging. 2011;39:13–26.
8.
Souvatzoglou M, Krause BJ, Pürschel A, et al. Influence of (11)C-choline PET/CT on the 
treatment planning for salvage radiation therapy in patients with biochemical recurrence 
of prostate cancer. Radiother Oncol. 2011;99:193–200.
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 
mild PSA increase. Eur J Nucl Med Mol Imaging. 2011;38:55–63.
10.
Giovacchini G, Picchio M, Scattoni V, et al. PSA doubling time for prediction of 
[(11)C]choline PET/CT findings in prostate cancer patients with biochemical failure after 
radical prostatectomy. Eur J Nucl Med Mol Imaging. 2010;37:1106–1116.
11.
Fuccio C, Castellucci P, Schiavina R, et al. Role of 11C-choline PET/CT in the restaging 
of prostate cancer patients showing a single lesion on bone scintigraphy. Ann Nucl Med. 
2010;24:485–492.


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12.
Seltzer MA, Barbaric Z, Belldegrun A, et al. Comparison of helical computerized 
tomography, positron emission tomography and monoclonal antibody scans for 
evaluation of lymph node metastases in patients with prostate specific antigen relapse 
after treatment for localized prostate cancer. J Urol. 2005;162:1322–1328.
13.
Kahn D, Williams RD, Manyak MJ, et al. 111Indium-capromab pendetide in the 
evaluation of patients with residual or recurrent prostate cancer after radical 
prostatectomy. The ProstaScint Study Group. J Urol. 1998;159:2041–6–discussion2046–
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Manyak MJ, Hinkle GH, Olsen JO, et al. Immunoscintigraphy with indium-111-capromab 
pendetide: evaluation before definitive therapy in patients with prostate cancer. Urology. 
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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 
Multidetector CT for Prostate Cancer Evaluations. Am J Nucl Med Mol Imaging. 
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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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Afshar-Oromieh A, Avtzi E, Giesel FL, et al. The diagnostic value of PET/CT imaging with 
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Appendices
Appendix 1 Schedule of Study Procedures and Assessments
Screening
(Day -90 to Day 1)
Imaging 
(Day 1)
Informed Consent
X
Inclusion/Exclusion Criteria Assessment
X
PSA
X
68Ga-PSMA-11 Administration
X
Imaging (PET/CT or PET/MRI)
X
Adverse Event Collection
X