Clinical trial NCT04614363
Conditions: Prostate Cancer High Risk
Keywords: PSMA 68 Ga
Sponsor: The Methodist Hospital Research Institute
Start date: 2020-10-13; Completion date: 2023-04-25
Enrollment: 80 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a prospective, single-center, open-label pilot study of 68GA-PSMA-11 given at a single time prior to PET/CT imaging in men with localized high risk prostate cancer or biochemical recurrence. The imaging agent (68 Ga-PSMA 11 will be administered on an outpatient basis. It will be administered prior to the PET/CT imaging. The objective is to evaluate the distribution of 68GA-PSMA-11 in tissues and to determine if this alters the planned clinical management.

Detailed description:
This is a prospective, open label, single-center, single-arm, pilot diagnostic accuracy study to evaluate the tissue distribution of 68Ga-PSMA Positron Emission Tomography (PET)/CT in 80 patients with high risk localized prostate cancer or biochemical recurrence.

Subjects will receive a single IV dose of 3-7 mCi of 68Ga-PSMA (study drug) followed by PET/CT imaging 60-90 minutes after injection. All patients will be closely monitored with vital signs (blood pressure and heart rate), before and 2 hours following radiotracer administration.

Patients will receive a phone call 2 days following PET/CT to assess for adverse events.

To minimize bias, all PET/CT images will be interpreted by a board-certified radiologist. The radiologist evaluating the images will be blinded to the final outcome, such as the histopathology of any biopsies and the outcome of subsequent imaging.

Patients with study-defined high-risk features who are eligible and scheduled for radical prostatectomy will undergo 68Ga-PSMA-11 PET/CT injection. The results of the 68Ga-PSMA-11 PET/CT may alter patient management in one of several ways, including the decision to not pursue surgical extirpation (e.g. in the event of extensive distant metastasis) in favor of systemic therapy. It is also possible that the extent of surgical resection may be altered, such as non-regional pelvic or retroperitoneal lymph node dissection. The alteration in planned surgical treatment from standard of care will be recorded as a secondary-end point.

Arms: arm 1: Comparison between the results of 68 Ga-PSMA PET/CT to conventional imaging (bone scan, CT) in men with high risk prostate cancer.
Interventions: intervention 1: 68Ga-PSMA
Intervention descriptions: intervention 1: All subjects enrolled in the study will receive a single IV dose of 3-7 mCi of 68 Ga-PSMA (study drug) followed by PET/CT imaging for detection of tumor location.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Comparison of 68Ga-PSMA Positron Emission Tomography (PET)/CT to 
Conventional Imaging in Men with High Risk Prostate  
 
Protocol Number: 
******** 
National Clinical Trial (NCT) Identified Number: 
04614363 
Principal Investigator: 
Brian J. Miles MD 
IND 
151520 
Funded by: 
Houston Methodist Research Institute 
 
 
Version Number: 5 
07/08/2021 


  
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Table of Contents 
STATEMENT OF COMPLIANCE ........................................................................... 1 
1 
PROTOCOL SUMMARY ................................................................................ 1 
1.1 
Synopsis .................................................................................................... 1 
Schema 4 
1.2 
Schedule of Activities (SoA) .................................................................... 6 
2 
INTRODUCTION ............................................................................................ 7 
2.1 
Study Rationale ......................................................................................... 7 
2.2 
Background ............................................................................................... 8 
2.3 
Risk/Benefit Assessment ........................................................................... 9 
2.3.1 
Known Potential Risks ................................................................ 9 
2.3.2 
Known Potential Benefits ........................................................... 9 
2.3.3 
Assessment of Potential Risks and Benefits ............................... 9 
3 
OBJECTIVES AND ENDPOINTS ................................................................10 
4 
STUDY DESIGN ............................................................................................11 
4.1 
Overall Design.........................................................................................11 
4.2 
Scientific Rationale for Study Design .....................................................14 
4.3 
Justification for Dose ..............................................................................14 
4.4 
End of Study Definition ..........................................................................15 
5 
STUDY POPULATION .................................................................................16 
5.1 
Inclusion Criteria .....................................................................................16 
5.2 
Exclusion Criteria ....................................................................................16 
5.3 
Lifestyle Considerations .........................................................................17 
5.4 
Strategies for Recruitment and Retention ...............................................17 
6 
STUDY INTERVENTION .............................................................................18 
6.1 
Study Intervention(s) Administration .....................................................18 
6.1.1 
Study Intervention Description .................................................18 
6.1.2 
Dosing and Administration .......................................................18 
6.2 
Preparation/Handling/Storage/Accountability ........................................19 
6.2.1 
Acquisition and accountability .................................................19 
6.2.2 
Formulation, Appearance, Packaging, and Labeling ................19 
6.2.3 
Product Storage and Stability ....................................................20 
6.2.4 
Preparation ................................................................................20 
6.3 
Measures to Minimize Bias: Randomization and Blinding ....................21 
6.4 
Study Intervention Compliance ..............................................................21 
6.5 
Concomitant Therapy ..............................................................................21 


  
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6.5.1 
Rescue Medicine .......................................................................21 
7 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ...............................................................22 
7.1 
Discontinuation of Study Intervention ....................................................22 
7.2 
Participant Discontinuation/Withdrawal from the Study ........................22 
7.3 
Lost to Follow-Up ...................................................................................23 
8 
STUDY ASSESSMENTS AND PROCEDURES..........................................23 
8.1 
Efficacy and SAFETY ASSESSMENTS ...............................................23 
8.2 
Adverse Events and Serious Adverse Events .........................................27 
8.2.1 
Definition of Adverse Events (AE) ..........................................27 
8.2.2 
Definition of Serious Adverse Events (SAE) ...........................27 
8.2.3 
Classification of an Adverse Event ...........................................28 
8.2.4 
Time Period and Frequency for Event Assessment and Follow-
Up 
29 
8.2.5 
Adverse Event Reporting ..........................................................30 
8.2.6 
Serious Adverse Event Reporting .............................................31 
8.2.7 
Reporting Events to Participants ...............................................33 
8.2.8 
Events of Special Interest ..........................................................33 
8.2.9 
Reporting of Pregnancy ............................................................33 
8.3 
Unanticipated Problems ..........................................................................33 
8.3.1 
Definition of Unanticipated Problems (UP) .............................33 
8.3.2 
Unanticipated Problem Reporting ............................................34 
8.3.3 
Reporting Unanticipated Problems to Participants ...................34 
9 
STATISTICAL CONSIDERATIONS ...........................................................35 
9.1 
Sample Size Determination .....................................................................35 
9.2 
Populations for Analyses .........................................................................35 
9.3 
Statistical Analyses .................................................................................35 
9.3.1 
General Approach .....................................................................35 
9.3.2 
Safety Analyses .........................................................................35 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ...............................................................................................36 
10.1 
Regulatory, Ethical, and Study Oversight Considerations......................36 
10.1.1 
Informed Consent Process ........................................................36 
10.1.2 
Study Discontinuation and Closure ..........................................37 
10.1.3 
Confidentiality and Privacy ......................................................38 
10.1.4 
Future Use of Stored Specimens and Data ...............................39 


  
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10.1.5 
Key Roles and Study Governance ............................................39 
10.1.6 
Safety Oversight ....................... Error! Bookmark not defined. 
10.1.7 
Clinical Monitoring ...................................................................39 
10.1.8 
Quality Assurance and Quality Control ....................................40 
10.1.9 
Data Handling and Record Keeping .........................................40 
10.1.10 
Protocol Deviations ...................................................................41 
10.1.11 
Publication and Data Sharing Policy ........................................42 
10.1.12 
Conflict of Interest Policy .........................................................43 
10.2 
Additional Considerations .......................................................................43 
10.3 
Abbreviations ..........................................................................................44 
10.4 
Protocol Amendment History .................................................................46 
11 
REFERENCES ...............................................................................................47 
 
 
 
Appendix A    
68GA-PSMA-11 Injection: Chemistry, Manufacturing , and  
Controls


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STATEMENT OF COMPLIANCE 
 
(1) The trial will be carried out in accordance with International Conference on 
Harmonization Good Clinical Practice (ICH GCP) and the following:  
 
• United States (US) Code of Federal Regulations (CFR) applicable to 
clinical studies (45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 
CFR Part 312, and/or 21 CFR Part 812)  
 
National Institutes of Health (NIH)-funded investigators and clinical trial 
site staff who are responsible for the conduct, management, or oversight of 
NIH-funded clinical trials have completed Human Subjects Protection and 
ICH GCP Training. 
 
The protocol, informed consent form(s), recruitment materials, and all 
participant materials will be submitted to the Institutional Review Board 
(IRB) for review and approval.  Approval of both the protocol and the 
consent form must be obtained before any participant is enrolled.  Any 
amendment to the protocol will require review and approval by the IRB 
before the changes are implemented to the study.  In addition, all changes to 
the consent form will be IRB-approved; a determination will be made 
regarding whether a new consent needs to be obtained from participants who 
provided consent, using a previously approved consent form. 
 
 
1  PROTOCOL SUMMARY 
1.1 SYNOPSIS  
Title: 
Comparison of 68Ga-PSMA Positron Emission Tomography 
(PET)/CT to Conventional Imaging in Men with High Risk 
Prostate Cancer  
Study 
Description: 
This is a prospective, single-center, open-label pilot study of 
68GA-PSMA-11 given at a single time prior to PET/CT 
imaging in men with localized high risk prostate cancer or 
biochemical recurrence.  Eligible participants will undergo 
baseline assessments using conventional 99-Tc Bone Scan and 
CT of the Abdomen and Pelvis or multi-parametric MRI 
imaging of the prostate  


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Objectives: 
 
Primary 
Objective 
 
 
 
1. To evaluate the tissue distribution of 68GA-PSMA-11 
PET/CT imaging in normal tissues and biopsy proven 
tumor and non-tumorous regions of the prostate, and also 
pelvic lymph nodes in high risk patients undergoing 
standard of care prostatectomy and bilateral lymph node 
dissection. 
 
2. To determine the proportion of patients in which 68GA-
PSMA-11 PET/CT altered the planned clinical 
management. 
 
Secondary 
Objective: 
1. To correlate the intensity of 68GA-PSMA-11 PET/CT 
uptake with respect to pathological findings.  
 
2. To compare suspicious lesions visualized on 68GA-
PSMA-11 PET /CT with standard of care diagnostic 
imaging modalities, additional biopsy results, or clinical 
follow-up performed at the discretion of the referring 
physician. 
 
 
Endpoints: 
Primary 
Endpoints: 
 
1. Proportion of patients with cTxNoMo (clinically 
localized 
disease) 
found 
on 
final 
histological 
examination to have lymph node involvement as 
determined by 68GA-PSMA-11 PET/CT. 
2. Proportion of patients in which 68GA-PSMA-11 
PET/CT altered the planned clinical management. 
 
Secondary 
Endpoints:  
 
1. 68GA-PSMA-11 PET/CT intensity is variable, and we 
will evaluate what intensity endpoint is predictable of 
tissue involvement. 
2. To compare and contrast findings in 68GA-PSMA-11 
PET/CT with standard diagnostic modalities of bone 
scan, CTs and MRIs. 


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Study Population: Male patients, aged 21 or older, diagnosed with 
histopathological proven prostate adenocarcinoma, with no 
evidence of other malignancy, and Eastern Cooperative 
Oncology Group (ECOG) performance of 0-1. 
 
Phase: 
 
Pilot, phase I/2 
 
Description of 
Sites/Facilities 
Enrolling 
Participants: 
 
This is a single site trial that will be conducted at the Houston 
Methodist Hospital.  
  
 
Description of 
Study 
Intervention: 
This is a prospective, open label, single-center, single-arm, pilot 
diagnostic accuracy study to evaluate the tissue distribution of 
68Ga-PSMA Positron Emission Tomography (PET)/CT in 80 
patients with high risk localized prostate cancer or biochemical 
recurrence. 
Subjects will receive a single IV dose of 3-7 mCi of 68Ga-PSMA 
(study drug) followed by PET/CT imaging 60-90 minutes after 
injection. All patients will be closely monitored with vital signs 
(blood pressure and heart rate), before and 2 hours following 
radiotracer administration. 
Patients will receive a phone call 2 days following PET/CT to 
assess for adverse events. 
To minimize bias, all PET/CT images will be interpreted by a 
board-certified radiologist. The radiologist evaluating the images 
will be blinded to the final outcome, such as the histopathology of 
any biopsies and the outcome of subsequent imaging.  
 
 Patients with study-defined high-risk features who are eligible and 
scheduled for radical prostatectomy or with biochemical 
recurrence will undergo 68Ga-PSMA-11 PET/CT injection. The 
results of the 68Ga-PSMA-11 PET/CT may alter patient 


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management in one of several ways, including the decision to not 
pursue surgical extirpation (e.g. in the event of extensive distant 
metastasis) in favor of systemic therapy. It is also possible that the 
extent of surgical resection may be altered, such as non-regional 
pelvic or retroperitoneal lymph node dissection. The alteration in 
planned surgical treatment from standard of care will be recorded 
as a secondary-end point.  
Study Duration: 
18 months. 
Participant 
Duration: 
6 months. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SCHEMA 
 
 
Screening 
Visit 1 
 
 
Total:80 patients - Obtain informed consent. Screen potential participants by inclusion 
and exclusion criteria; obtain history, physical exam, height/weight, ECOG, safety labs 


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Visit 2 
 
 
 
 
 
 
 
 
 
 
 
Visit 3 and 4 
 
 
 
 
Administration of study intervention. 
AE assessment (Phone follow-up) 
 
Follow up at 2 and 6 months  
 
Radical Prostatectomy 
Systemic Therapy to be 
determined attending 
physician if metastatic disease 
is identified 


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1.2 SCHEDULE OF ACTIVITIES (SOA) 
The schedule below is provided as an example and should be modified as 
appropriate.  
 
 
 
 
 
  
Screening 
Enrollment 
Post 
Dose 
  
Surgery/Pre-
surgery 
Follow 
up/Early 
Termination 
Follow 
up 
Follow 
up 
  
Day -28 to 0 
Day 0 
Day 0: 
Hour 1-
2 
Day 2 
Day 10       
+/- 7 
Month 2 
+/- 7 
Month 
6 +/- 7 
  
Visit 1 
Visit 2 
  
Phone 
call 
  
Visit 3 
Visit 4 
Informed Consent 
R 
  
  
  
  
  
  
Demographics 
R 
  
  
  
  
  
  
Inclusion/Exclusion 
Criteria 
R 
  
  
  
  
  
  
Medical History1 
R 
  
  
  
  
  
  
Performance Status 
R 
  
  
  
  
  
  
Vital Signs2 
R 
  
R3 
  
  
  
  
Administer Study 
Intervention 68Ga 
PSMA 11 
  
R 
  
  
  
  
  
Whole body 
PET/CT 
  
R 
  
  
  
  
  
PSA 
R 
  
  
  
  
SOC 
SOC 
Bone Scan 4 
SOC 
  
  
  
  
  
  
CT abdomen/pelvis 
4 
SOC 
  
  
  
  
  
  
MRI of prostate 
SOC 
  
  
  
  
  
  
Adverse event 
evaluation 
  
  
R 
R 
R 
  
  
Prostate Biopsy 
SOC 
  
  
  
  
  
  
Telephone call 
  
  
  
R 
  
  
  
Prostatectomy 
  
  
  
  
SOC 
  
  


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Pathology 
porcessing 
  
  
  
  
SOC 
  
  
 
 
1  Medical history includes review of prostate cancer treatment and prior radiographic exams.  
2 Vital Signs Assessment includes measurement of blood pressure and heart rate.  
3 On days of dosing, vital signs will be collected pre-dose and post-dose. 
4 If not performed within 6 months of Screening, diagnostic CT or MR scans and or Bone scan 
are to be obtained prior to surgery, only if clinically indicated 
 
 
2  INTRODUCTION 
 
 
2.1 STUDY RATIONALE  
 
Prostate cancer (PCa) remains the most common non-cutaneous cancer diagnosis in 
males, with an estimated 174,650 new cases in 2019[2]. After lung cancer, PCa 
accounts for the second highest mortality in men. Localized PCa, often screen-
detected using prostate specific antigen (PSA) based blood tests, is highly variable 
in clinical course and risk of progression. Treatment is therefore matched on this 
basis, and includes Active Surveillance for Low-Risk PCa, whereas Intermediate-
and High-Risk PCa are treated by radiation therapy (external beam or 
brachytherapy) or surgery (radical prostatectomy). While durable cure can be 
achieved by these modalities,  biochemical relapse occurs in approximately 35% of 
who have undergone treatment for localized disease[3]. 
There is significant interest in identifying individuals at highest risk of 
biochemical relapse, using a variety of approaches, including genomic-based 
biomarkers. Identification of metastatic disease beyond of the prostate is critical, not 
only for potentially targeted local-therapy (e.g. surgical resection of recurrence or 
targeted radiation therapy) but earlier use of aggressive adjuvant radiation or 
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the prostate has been limited by the sensitivity of cross-sectional tomography (CT), 
which relies on nodal morphology (size). The sensitivity of CT or MRI based 
imaging for the detection lymph node metastasis is in the range of 30-80%[4]. 
Detection of bone metastasis once present as osteoblastic lesions can be identified 
by bone-scintigraphy, again with limed sensitivity, especially in asymptomatic 
patients with PSA levels below 20[5]. In spite of these limitations, CT and whole 
body bone scans are widely accepted as the primary imaging modality for staging 
patients, particularly with localized PCa.  
 
2.2 BACKGROUND  
Molecular imaging using various targets and positron emission tomography (PET) 
tracers have been used to improve detection of recurrent prostate cancer. 18F- or 
11C labeled choline as well as 11C-acetate have been previously investigated[6,7].  
Their clinical utility has been limited by non-specific uptake in benign tissue, 
including benign prostatic hypertrophy[8].  18F-Fluciclovine has recently been 
approved owing to it improvement over 11C[9]. Targeting of prostate-specific 
membrane antigen (PSMA) by radiotracer has gained the most contemporary clinical 
interest. PSMA (glutamate carboxypeptidase II, N-acetyl-a-linked acidic dipeptidase 
I, or folate hydrolase) is a type II transmembrane glycoprotein belonging to the M28 
peptidase family is preferentially overexpressed in prostate cancer cells relative to 
other cells. Other tissues may also express PSMA, including kidney, small intestine 
or salivary glands. Importantly, PSMA expression is maintained and may increase 
through the full spectrum of prostate cancer, including advanced disease[10].   
Methods have focused on labeling ligands (Glu-NH-CO-NH-Lys-(Ahx)-
[68Ga(HBED-CC)] also known as 68-PSMA-11) to PSMA with 68-Ga, allowing 
internalization and significant differential contrast between normal and cancerous 
tissues which aids in optimal imaging characteristics[11,12]. Initial studies showed 
that labeling of PSMA-ligand with 68-Ga allowed improved identification of PCa 
recurrence and metastasis [13].  
 
Early data has demonstrated the utility of 68Ga-PSMA with respect to improved 
accuracy of detection and in turn significant impact on  treatment decisions[14]. A 
recent meta-analysis of 68Ga-PSMA PET studies showed promising detection of 
metastasis following biochemical recurrence, even at low PSA levels [PSA >0.2 


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ng/ml (33% detection rate) and PSA 0.2–0.5 ng/ ml (45% detection rate)][15]. 
Importantly, the vast majority of these studies have been reported from 
retrospective data. 
 
In our study we plan to prospectively study the accuracy and utility of 68Ga-
PSMA 11 and its impact of the treatment related decisions. 
 
 
2.3 RISK/BENEFIT ASSESSMENT   
 
2.3.1 KNOWN POTENTIAL RISKS  
 
2.3.2 KNOWN POTENTIAL BENEFITS  
 
 
The investigational study may determine the presence of disease outside of the 
prostate that is resectable at the time of the surgery and that may improve long 
term outcomes. 
 
 
2.3.3 ASSESSMENT OF POTENTIAL RISKS AND BENEFITS  
 
• Study Imaging Drug Risk: Possible side effects such as rash, nausea, 
headache or fatigue. In clinical studies that used 68Ga-PSMA-11 in the 
same amount being used in this study, no serious adverse events were 
reported.  
• PET/CT scan radiation risk:  the maximum amount of radiation from this 
study is equivalent to 2.43 mSv and less than 1 mSv for non-diagnostic CT 
scan performed to process the PET data. The total radiation dose from the 
study procedure is less than 1/10th the annual exposure allowed for 
occupational workers. Although there are no proven harmful effects from 
this amount of radiation, long-term effects, such as cancer, cannot be ruled 
out with certainty. This dose estimate takes into account only the exposure 
to research procedures in this study. 
• Other risk: pain and infection at the site of the needle stick for the study 
drug injection or for blood drawn for the blood tests. 
 
 
 


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3 OBJECTIVES AND ENDPOINTS 
 
OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
Primary 
 
 
 
1. To evaluate the tissue 
distribution of 68GA-
PSMA-11 PET/CT 
imaging in normal 
tissues and biopsy 
proven tumor and 
non-tumorous regions 
of the prostate, and  
also pelvis    lymph 
nodes in patients 
undergoing standard 
of care prostatectomy 
and bilateral lymph 
node dissection in 
high risk patients 
 
2. To determine the 
proportion of patients 
in which 68GA-
PSMA-11 PET/CT 
altered the planned 
clinical management 
 
 
1. Proportion of 
patients with 
cTxNoMo 
(clinically 
localized 
disease) found 
on final 
histological 
examination to 
have lymph node 
involvement as 
determined by 
68GA-PSMA-11 
PET. 
 
2. Proportion of 
patients in which 
68GA-PSMA-11 
PET/CT altered 
the planned 
clinical 
management. 
 
 
1. Determining the usefulness 
of PSMA PET/CT requires 
defining its’ ability to 
identify lymphatic or 
metastatic spread that 
heretofore has not been 
detectable by standard 
radiographic means. 
 
2. Understanding whether and 
why 68GA-PSMA-11 
PET/CT findings alter 
treatment plans is critical in 
defining its role in the 
diagnostic tools urologists 
use to manage their patients 
with prostate cancer. 
Secondary 
 
 
 
 
1. To correlate the 
intensity of 68Ga-
PSMA-11 uptake 
 
1. 68Ga-PSMA-11 
PET/CT 
intensity is 
variable, and we 
will evaluate 
 
1. To identify those 
patients in whom more 
localized or extended 
therapy might be 
indicated, it is important 


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OBJECTIVES 
ENDPOINTS 
JUSTIFICATION FOR 
ENDPOINTS 
with respect to 
pathological findings. 
 
2. To  Compare 
suspicious lesions 
visualized on 68Ga-
PSMA-11 PET/CT 
with standard of care 
diagnostic imaging 
modalities, additional 
biopsy results, or 
clinical follow-up 
performed at the 
discretion of the 
referring physician 
 
 
what intensity 
endpoint is 
predictable of 
tissue 
involvement. 
 
2. To compare and 
contrast findings 
in 68Ga-PSMA-
11 PET/CT with 
standard 
diagnostic 
modalities of  
bone scans, CTs 
and MRIs 
 
 
 
 
to know in equivocal 
68Ga-PSMA PET/CT 
readings what the true 
positive results 
histopathologically are 
in order to avoid 
possible over / under 
treatment. 
 
2.  Based on histologic 
results comparing 
standard radiographic 
modalities to 68Ga 
PSMA 11 PET/CT 
findings will add value 
as to whether they are 
complimentary or one or 
more might be deleted in 
the workup of these men. 
. 
 
 
 
4 STUDY DESIGN  
 
4.1 OVERALL DESIGN 
This is a prospective, open label, single-center, single-arm, pilot diagnostic 
accuracy study to evaluate the tissue distribution of 68Ga-PSMA Positron 
Emission Tomography (PET)/CT in 80 patients with high risk localized prostate 
cancer or biochemical recurrence. 
 
At screening: participants will sign an approved informed consent, medical history 
and vital signs will be completed. Labs will be drawn for PSA. Eligibility criteria 
will be verified and completed.  
 
Day of the injection: 


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 Subjects will receive a single IV dose of 3-7 mCi of 68Ga-PSMA (study drug) 
followed by PET/CT imaging 60-90 minutes after injection. Scan time will be 
determined based on the capacity of the PET scanner. Scanning will start from the 
mid-thighs (to minimize radiotracer artifact from accumulation in the bladder) to 
the base of the skull. There may be exceptions based on clinical relevance that the 
scan coverage may be extended.  
All patients will be closely monitored with vital signs, to be assessed before and 
after injection of 68Ga-PSMA-11 (Blood Pressure, Heart Rate). Patients will be 
monitored with respect to vital signs and adverse events during, and 2-hours 
following radiotracer administration for adverse events.  
 
Post injection: 
 Patients will receive a phone call 2 days following PET/CT to assess for adverse 
events that may have develop in a delayed fashion. If there are any concerning 
study-related adverse events, this will be escalated to clinical evaluation by the 
study primary investigators.  
 
 
To minimize bias, all PET/CT images will be interpreted by a board certified 
radiologist with experience in reading such modalities. They will be blinded to the 
final outcome, such as the histopathology of any biopsies and the outcome of 
subsequent imaging.  
 
68-Ga-PSMA PET/CT positivity or negativity will be interpreted, stratified by 
different anatomic regions as previously defined [1].  
 
REGION DESCRIPTION 
1 
Prostate and Prostate  Bed 
2 
Pelvis, excluding prostate bed, but including lymph nodes 
3 
Extra-pelvic soft tissue, including lymph node involvement and 
metastasis to other organs  
4 
Bone Metastasis 


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The presence of prostate cancer (positive or negative) will be reported within these 
regions.   
A. Lymph nodes - considered positive if the 68Ga-PSMA-11 uptake is 
localized/focal and is greater than the adjacent or mediastinal blood pool. The 
location of the lymph nodes will be recorded according to one of 7 sub-
categories as previous defined[1]:  
1 
Right 
Hypogastric/Internal-
iliac 
2 
Left 
Hypogastric/Internal-
iliac 
3 
Right Obturator 
4 
Left Obturator 
5 
Right External-iliac 
6 
Left External-iliac 
7 
Other 
 
B. Visceral lesions – These will be considered positive if the 68Ga-PSMA-11 
uptake is focal and greater than the physiologic background activity in the 
organ of interest.  
C. Bone lesions – These will be considered positive if the 68Ga-PSMA-11 
uptake is focal and greater than physiologic background activity in normal 
bone marrow.  
D. Prostate bed – These will be considered positive if the 68Ga-PSMA-11 
activity is focal and greater than the physiologic, background activity in the 
prostate bed.  
 
Validation of positive 68Ga-PSMA-11 will be based on a combination of histo-
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true positivity and false negative based on imaging follow previously published 
methodology[1].  
 
Surgery (prostatectomy) will take place between 7 3 and 14 days after the 68Ga-
PSMA 11 injection. 
 
If patients with BR show metastasis, attending urologist will evaluate for surgery, 
radiation or chemotherapy.  
  
Follow up in clinic will occur at 2 and 6 months after study drug injection. (Visits 
3 and 4) 
 
In patients with biochemical recurrence, will repeat the PSMA scan within 1 year, 
after they completed treatment and when their PSA still increases  when initial 
PSMA was negative, at PI’s discretion if needed. 
 
 
See Appendix 1.   Schedule of Events table 
 
 
4.2 SCIENTIFIC RATIONALE FOR STUDY DESIGN 
 
This is an exploratory, single arm, open label pilot study evaluation of  68Ga-
PSMA Positron Emission Tomography with intraprostatic and/or pelvic lymph 
node uptake determination by PET/CT imaging, with histological confirmation of 
disease localized and staging. Methodical evaluation of 68Ga-PSMA intraprostatic 
and or pelvic lymph node will provide important preliminary data upon which 
further clinical studies can be based. 
 
 
4.3 JUSTIFICATION FOR DOSE 
 
68Ga-PSMA-11 will be used as the radiopharmaceutical agent for PET imaging at 
a dose of 3-7 mCi given intravenously. Dosimetry data are available from 
published data and will reference the Weil Cornell IND application to the FDA.  


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In summary, the published literature and safety studies in humans indicates no 
observed adverse events to the radiopharmaceutical[1,7,16].  Measured dosimetry 
showed that the critical organs affected are, in descending order, the spleen, 
stomach wall, pancreas and bladder. The reported effective dose of 68Ga-PSMA-
11 is 0.0129 mSv/MBq, which is the lowest of the 68Ga based tracers, including 
those used in imaging of neuro-endocrine tumours such as  DOTA-TOC, DOTA-
NOC, DOTA-TATE[17–19].  
68Ga-PSMA can only be administered via intravenous infusion.  The proposed 
dose (3-7 mCi) is based upon joint guidelines from the European Association of 
Nuclear Medicine and The Society of Nuclear Medicine and Molecular Imaging, 
who recommend a dose of 0.049-0.06 mCi/kg.  In an average 75kg adult patient, 
this would be approximately 3.7-4.5 mCi [20]. 
The 68-Ga-PSMA agent will be manufactured using previously reported 
procedures using a generator. Agent release criteria, and validation standards for 
each batch produced will be followed.  
 
 
 
4.4 END OF STUDY DEFINITION 
 
A participant is considered to have completed the study if he has completed all 
phases of the study including the last visit or the last scheduled procedure shown in 
the Schedule of Activities (SoA), Section 1.3. 
Patients who do not complete surgery would be considered Early Termination (pre-
surgery). 
The investigator may withdraw a subject from the trial for any of the following 
reasons: 
1. Protocol violation, 
2. Serious or intolerable  adverse event (that in the opinion of the Investigator, 
requires the subject’s discontinuation), 
3.  The Investigator withdraws the subject (at the Investigator’s discretion for 
reasons other than an adverse event), 
4. The Principal Investigator terminates the study, 
5. The subject requests to be discontinued from the study, or 
6. The subject is lost to follow-up. 
 
 


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5 STUDY POPULATION 
 
5.1 INCLUSION CRITERIA 
1) Male aged 21 years or older 
2) Ability to understand and provide written informed consent 
3) All patients must have histopathological proven adenocarcinoma of the 
prostate 
4) ECOG performance status 0-1 
5) No evidence of other malignancy (except squamous or basal cell skin 
cancers) 
6)  Consent to use acceptable form of birth control following the imaging 
period (condoms for a     period of seven days after injection if sexually 
active) 
 
 
7)  a)  inclusion criteria specific for the pre-prostatectomy group:  
Untreated prostate Cancer with high-risk features, as defined as having at 
least one of the following criteria:  
i. PSA ≥ 20.0 ng/mL  
ii. ISUP Gleason Grade Group 3, 4 or 5  
iii.  Clinical stage T3 
b)  inclusion criteria specific for biochemical recurrence: 
(i) Histopathological proven prostate adenocarcinoma 
(ii)Rising PSA after definitive therapy with 
prostatectomy or radiation (therapy (external beam or 
brachytherapy). 
1. Post radical prostatectomy (RP), PSA greater than or equal to 0.2 
ng/ml measured more than 6 weeks after RP. 
2. Post-radiation therapy, PSA that is equal to or greater than 2 ng/ml 
rise above PSA nadir 
 
 
 
 
5.2 EXCLUSION CRITERIA 
 
1) Unable to tolerate a PET/CT (e.g. unable to lie flat) 


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2) Recent history of a secondary malignancy in the past year, excluding non-
melanoma skin cancer (non-metastatic) 
3) Known allergic reactions to 68-Ga, or gadolinium-based contrast agents. 
4) Treatment with another investigational drug or other intervention 2 years. 
5) Patient has any medical, psychological or social condition that, in opinion 
of the investigator will make difficult for the participant to tolerate study 
intervention. 
 
 
 
 
5.3 LIFESTYLE CONSIDERATIONS 
 
5.3.1 Fluid and Food Intake 
Subjects should follow their normal diet before and after the administration of the 
study drug. Subjects will be encouraged to increase fluid intake at baseline and 
after the image acquisition to maintain proper hydration throughout the study 
period and decrease radiation exposure to the urinary bladder. To enhance imaging, 
subjects will be encouraged to void prior to collection of study imaging post-68Ga-
PSMA-11 injection. 
 
There are no dietary or food restrictions for this trial. 
 
5.3.2 Subject Activity Restrictions 
The radioactivity administered in this study is similar to other radiopharmaceutical 
studies, therefore the only activity restriction is: 
 
• Participants whom are sexually active are required to consent to use 
acceptable form of birth control following the imaging period (condoms for 
a period of seven days after injection if sexually active) 
 
 
 
5.4 STRATEGIES FOR RECRUITMENT AND RETENTION 
 
• Target study sample: 80 male patients, age 21 and older, diagnosed with 
high risk adenocarcinoma of prostate. We anticipate will need to screen 200 
patients in order to reach the target enrollment. Study will enroll participants 


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from Houston Methodist Hospital-Department of Urology, or from external 
referrals by sub-investigators or other physicians. Once a possible candidate 
is identified, the study team will approach him over the phone/e-mail or 
personally during a standard of care appointment, to present information 
about the study. If patient expresses interest, he will be scheduled for a 
screening visit. 
 
 
 
6 STUDY INTERVENTION 
 
6.1 STUDY INTERVENTION(S) ADMINISTRATION 
 
6.1.1 STUDY INTERVENTION DESCRIPTION 
See Appendix A 
Study Drug 
Each milliliter of the sterile, apyrogenic drug product contains approximately 18.5-
74 MBq (0.5 – 2 mCi) of active ingredient (68Ga-PSMA-11), 6 mL of sodium 
chloride (Sodium Chloride Injection (0.9%) without preservatives USP), and 10% 
of ethanol (v/v). Each dose of 68Ga-PSMA-11 solution for intravenous injection 
should be stored at room temperature and administered by the labeled expiration 
time. 
 
6.1.2 DOSING AND ADMINISTRATION 
 
On Day 0 of the study, the study drug dose will be 185±74 MBq (5±2 mCi) and 
will be administered by IV injection as a slow bolus and flushed with 
approximately 10 mL of saline solution. 
A whole-body positron emission tomography/Computed Tomography (PET/CT) 
scan will be obtained between 60-90 minutes post-injection of study drug. 
 
Vital signs (BP and pulse) will be taken and recorded before injection and 2 hours 
post injection. 
 


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All study drug administration will be done at the clinical site under the supervision 
of the Investigator. 
 
Details of study drug administration will be captured in each subject’s source 
document and transcribe onto the case report form (CRF)  
 
 
6.2 PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
 
6.2.1 ACQUISITION AND ACCOUNTABILITY 
 
 
In accordance with International Conference on Harmonisation (ICH) and US 
Food and Drug Administration (FDA) requirements, the Investigator and/or Drug 
Dispenser must at all times be able to account for all study drug. 
 
No study agent is to be used outside of this study. Record the use of the study 
agent on the appropriate record. All study radiopharmaceuticals must be accounted 
for, whether used or unused, during the course of and at the conclusion of the 
study. 
  
The Investigator is responsible for ensuring that study drugs are recorded, handled 
and stored safely and properly in accordance with the Code of Federal Regulations 
(CFR), local/state laws and used in accordance with this protocol. 
 
68Ga-PSMA 11 will be manufactured by the Cyclotron cGMP Core Facility at 
Houston Methodist Research Institute. 
 
Principal Investigator will send requisition via email for the preparation of the 
product. The study drug will be dispensed in a sterile 10 ml polypropylene at room 
temperature to be administered to the subject. 
 
Unused product will be disposed of according to institutional regulations. Record 
the use and/or disposal of the study agent on the Drug Accountability record. 
 
 
 
6.2.2 FORMULATION, APPEARANCE, PACKAGING, AND 
LABELING 


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Formulation and packaging: the finished final product 68Ga-PSMA-11 solution for 
intravenous administration contains 0.6 ml ethanol and 5.4 ml of sodium chloride 
(Sodium Chrloride Injection (0.9%) without preservatives USP, in a 30 ml sterile 
vial. 
Appearance: It is clear and colorless solution, no visible particles. 
Dispensing: The product solution is aseptically dispensed into a sterile 10-mL 
polypropylene syringe and stored at room temperature prior to its intravenous 
administration to the subject. 
Labeling: the label will disclose the expiration date and “For investigational use 
only”. 
 
 
6.2.3 PRODUCT STORAGE AND STABILITY 
 
 
Each dose of 68Ga-PSMA-11 solution for intravenous injection will be shipped to 
the PET Imaging Core and it should be stored at room temperature and 
administered before the labeled expiration time. 
 
The drug product contains radioactive material and should only be handled by 
personnel trained in the use of radioactive isotopes with proper shielding and 
monitoring. Receipt and use is limited to a facility licensed by the Federal or State 
office of Radioactive Substances. Unused or residual waste should be disposed of 
as radioactive waste following the institution’s standard operating procedures 
(SOPs) and/or applicable regulations or guidance. 
 
 
 
6.2.4 PREPARATION 
 
The drug will be manufactured upon requisition from a qualified principle 
investigator with approved IND and IRB protocol. During drug product 
manufacturing, individual doses are aseptically dispensed into a sterile 10-mL 
polypropylene syringe and stored at room temperature prior to its intravenous 
administration to the patient. Each milliliter of the sterile, apyrogenic drug product 
contains approximately 18.5-75 MBq (0.5 – 2 mCi) of active ingredient (68Ga-
PSMA-11), 0.9 mL of sodium chloride (Sodium Chrloride Injection (0.9%) without 
preservatives USP, and 0.1 mL of ethanol. 


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The drug product contains radioactive material and should only be handled by 
personnel trained in the use of radioactive isotopes with proper shielding and 
monitoring. Receipt and use is limited to a facility licensed by the Federal or State 
office Radioactive Substances. Unused or residual waste should be disposed of a 
radioactive waste following the institution’s standard operating procedures (SOPs) 
and/or applicable regulations or guidance. Each dose of 68Ga-PSMA-11 solution 
will be administered as a slow bolus over approximately 30 sec followed by a 10 
mL saline flush. 
 
 
 
6.3 MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND 
BLINDING 
 
To minimize bias, all PET/CT images will be interpreted by a board-certified 
radiologist. The radiologist evaluating the images will be blinded to the final 
outcome, such as the histopathology of any biopsies and the outcome of 
subsequent imaging.  
 
 
 
6.4 STUDY INTERVENTION COMPLIANCE 
 
To ensure maximum compliance, all doses of study drug solution will be 
administered by study staff. 
Source documents will be completed with all relevant information. These will 
include: dose, time, vital signs (pre and post injection) and any side effects if 
occurred during procedures. 
 
6.5 CONCOMITANT THERAPY 
 
Not applicable  
 
6.5.1 RESCUE MEDICINE 
 
Not applicable  


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7 STUDY INTERVENTION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
 
7.1 DISCONTINUATION OF STUDY INTERVENTION 
 
 
Participant will be discontinued from the study if they are not able to lie on their 
back  in the scanner table for 15-20 during the procedure or if the suffer from 
claustrophobia. This will be documented in the CRF with date and specific reason 
for discontinuation of the participant. 
 
7.2 PARTICIPANT DISCONTINUATION/WITHDRAWAL FROM THE 
STUDY 
 
Participants are free to withdraw from participation in the study at any time upon 
request. 
An investigator may discontinue or withdraw a participant from the study for the 
following reasons: 
 
• Significant study intervention non-compliance  
• If any clinical adverse event (AE), laboratory abnormality, or other medical 
condition or situation occurs such that continued participation in the study 
would not be in the best interest of the participant 
• Disease progression which requires discontinuation of the study intervention 
• If the participant meets an exclusion criterion (either newly developed or not 
previously recognized) that precludes further study participation 
The reason for participant discontinuation or withdrawal from the study will be 
recorded on the Case Report Form (CRF). Subjects who sign the informed consent 
form and are screened but do not receive the study intervention may be replaced.  
Subjects who sign the informed consent form, and are screened and receive the 
study intervention, and subsequently withdraw, or are withdrawn or discontinued 
from the study, will not be replaced. 
 


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7.3 LOST TO FOLLOW-UP 
 
A participant will be considered lost to follow-up if he or she fails to return for 
scheduled visits and is unable to be contacted by the study site staff.  
 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• The site will attempt to contact the participant and reschedule the missed 
visit, during the following week and counsel the participant on the 
importance of maintaining the assigned visit schedule and ascertain if the 
participant wishes to and/or should continue in the study. 
• Before a participant is deemed lost to follow-up, the investigator or designee 
will make every effort to regain contact with the participant (where possible, 
3 telephone calls and, if necessary, a certified letter to the participant’s last 
known mailing address or local equivalent methods). These contact attempts 
should be documented in the participant’s medical record or study file.  
• Should the participant continue to be unreachable, he or she will be 
considered to have withdrawn from the study with a primary reason of lost 
to follow-up. 
 
 
8 STUDY ASSESSMENTS AND PROCEDURES 
 
8.1 EFFICACY AND SAFETY ASSESSMENTS  
 
8.1 Informed Consent 
All subjects must sign and personally date an IRB approved informed consent form 
after receiving detailed written and verbal information about the reason, the nature 
and the possible risks associated with the administration of the study agent prior to 
the initiation of any study-related procedures. This must be done according to the 
guidelines provided in the Declaration of Helsinki, ICH E6 Guideline for Good 
Clinical Practice (GCP), and requirements of Title 21 CFR 50.20 through 50.27. 
The subject must be made aware and agree that personal information may be 
scrutinized during an audit by competent authorities and properly authorized 
persons. However, personal information will be treated as strictly confidential and 
will not be publicly available. 
 
8.2 Medical History 


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A complete medical history, including prostate cancer history, will be obtained at 
the first screening visit. Site staff will record the subject’s medical history in the 
subject’s source records and transcribe the information onto the medical history 
section of the CRF. Historical information concerning allergies (including food, 
drug and/or environmental) will also be obtained. 
 
8.3 Vital Signs 
Vital signs will include measurement of blood pressure and heart rate. Vital signs 
will be obtained and recorded at the Screening visit, pre- and post- each study drug 
injection, and also 2 hours after the first injection. 
 
8.4 Dispensing Study Drug 
The radiopharmaceutical will be injected through the indwelling catheter at a 
185±74 MBq (5±2 mCi) dose. The estimated radioactive dose will be determined 
by measuring the amount of radioactivity in the syringe pre- and post-injection, 
using an appropriately calibrated radioisotope dose calibrator in accordance with 
the nuclear medicine department’s SOPs. The injected activity will be recorded in 
the subject’s source records and transcribed into the CRF. 
The injection will be given by slow intravenous bolus. Following completion of the 
68Ga-PSMA-11 injection, a normal saline flush (approximately 10 mL) will ensure 
that all 168Ga-PSMA-11 remaining in the infusion line is injected. 
Any administration complication of the drug (e.g., overdose, observable 
extravasation, medication error) will be reported to the Chief of Nuclear Medicine 
and the PI within 24 hours of the event and will be recorded in the subject’s source 
records and transcribed onto the CRF. If the Chief of Nuclear Medicine and the PI 
determine an adverse event occurred after injection or because of extravasation this 
will be reported as outlined in Section 7. 
 
8.5 Computed Tomgraphy (CT) and Magnetic Resonance (MR) Imaging 
A diagnostic quality MR scan (abdomen and pelvis) may be obtained (if clinically 
indicated) prior to surgery if not done within  6 months of the screening visit, if 
clinically indicated. If collected as part of screening procedures, the scan should be 
contrast-enhanced, unless contra-indicated for the subject. If necessary, the scan 
maybe obtained between the first injection of study drug and surgery. 
 
8.6 Bone Scan 
If clinically indicated, a bone scan may be obtained prior to surgery if not done 
within   6 months of the screening visit. If necessary, the scan may be obtained 
between the first injection of study drug and surgery. 
 


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8.7 68Ga-PSMA-11 PET/CT Imaging 
A whole-body positron emission tomography/Computed Tomography (PET/CT) 
scan will be obtained between 60-90 minutes post-injection of study drug. 
 
8.7.1 Imaging Procedures 
 
68-Ga-PSMA PET/CT positivity or negativity will be interpreted, stratified by 
different anatomic regions as previously defined[1].  
 
REGION DESCRIPTION 
1 
Prostate/Prostate  Bed 
2 
Pelvis, excluding prostate bed, but including lymph nodes 
3 
Extra-pelvic soft tissue, including lymph node involvement and 
metastasis to other organs  
4 
Bone Metastasis 
 
The presence of prostate cancer (positive or negative) will be reported within these 
regions.   
A. Lymph nodes - considered positive if the 68Ga-PSMA-11 uptake is 
localized/focal and is greater than the adjacent or mediastinal blood pool. The 
location of the lymph nodes will be recorded according to one of 7 sub-
categories as previous defined[1]:  
1 
Right 
Hypogastric/Internal-
iliac 
2 
Left 
Hypogastric/Internal-
iliac 
3 
Right Obturator 
4 
Left Obturator 
5 
Right External-iliac 
6 
Left External-iliac 
7 
Other 


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B. Visceral lesions – These will be considered positive if the 68Ga-PSMA-11 
uptake is focal and greater than the physiologic background activity in the 
organ of interest.  
C. Bone lesions – These will be considered positive if the 68Ga-PSMA-11 
uptake is focal and greater than physiologic background activity in normal 
bone marrow.  
D. Prostate bed – These will be considered positive if the 68Ga-PSMA-11 
activity is focal and greater than the physiologic, background activity in the 
prostate bed.  
 
 
8.7.1.1 Camera Quality Control 
Quality control of the PET/CT scanner will be maintained throughout the study 
according to departmental SOPs. 
 
8.7.1.2 Image Acquisition 
PET scan and Quantitation: Following administration of Ga-68 tracer, each subject 
will have a PET/CT scans at 60-90 min on a Siemens mCT PET/CT scanner 
by using 10-12 bed positions and 3 min/bed. The CT parameters used for 
attenuation correction CT (CAREDose-4D) include a fixed 100 mA tube current 
and a peak voltage of 120 kVp with a 5-mm reconstruction interval. The PET scans 
will be reconstructed by using a Siemens time of flight reconstruction method, 
TrueX-TOF UltraHD-PET with a Gaussian filter, scatter correction, and 5/21 
iterations/subsets. 
 
For the study, using the decay-corrected coronal anterior maximum- intensity 
projections of PET scans, regions of interest (ROI) will be drawn manually around 
the major organs (liver, kidney, spleen, lungs, heart) and any other tissues (tumor, 
muscle) showing visually appreciable Ga-68 uptake. Time-activity curves will be 
constructed by using values of whole-organ activity at the time of imaging. 
Recently, several 18F labeled peptides have been evaluated for imaging studies 
and methods for quantifying biodistribution and tumor localization have been 
described. 
We plan to follow similar methods in our protocol. The percent injected dose in 
each ROI and the clearance kinetics from each organ will be used to estimate the 
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In order to generate quantitative data of tumor localization for each Ga-68 tracer, 
SUVmean and SUVmax will be generated as previously described. When there is 
no resolution loss or uncertainty in the ROI boundary definition (such as in the 
liver), SUVmean will produce a reliable estimate. However, SUVmax may be a 
more reliable parameter since the maximum value within an ROI is typically 
invariant with respect to small spatial shifts of the ROI. 
 
8.8 Prostatectomy 
Subjects will undergo standard of care surgery as deemed appropriate by the 
patient’s attending urologist. 
 
8.9 Surgical Pathology 
Following radical prostatectomy and/or pelvic lymph node dissection, surgical 
specimens will be brought on ice to the Department of Surgical Pathology for 
tissue processing. Prostatectomy and lymph node specimens will be processed by 
the Department of Pathology in the standard fashion with hematoxylin and eosin 
(H&E) staining for grading and staging. Additionally, immunohistochemistry will 
be performed to confirm, at a microscopic level, that radiolabeled 68Ga-PSMA-11 
co-localizes with tumor foci seen on H&E sections. Tumor foci identified on H&E 
sections will serve as the gold standard for imaging comparison. 
 
 
8.2 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
 
8.2.1 DEFINITION OF ADVERSE EVENTS (AE) 
An adverse event (AE) is any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product, at any dose, which 
does not necessarily have a causal relationship with the treatment. 
An adverse event (AE) can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding, for example), symptoms or disease 
temporally associated with the use of a medicinal product, whether or not 
considered related to the medicinal product. 
 
8.2.2 DEFINITION OF SERIOUS ADVERSE EVENTS (SAE)  
 
A serious adverse event (SAE) is any untoward medical occurrence that at any 
dose falls into one or more of the following categories: 
• results in death 


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• is life-threatening 
• i.e., an event which, in the view of the Investigator, places the subject at 
immediate risk of death from the event as it occurred and does not include an 
event which hypothetically might have caused death if it were more severe 
• requires inpatient hospitalization or prolongation of existing hospitalization. 
 For the seriousness criterion of inpatient hospitalization to apply, an overnight 
stay in the hospital is required. Admission to an ER and release without an 
overnight stay would not satisfy the inpatient hospitalization seriousness 
criterion. 
• results in persistent or significant disability/incapacity 
• where disability is defined as a substantial disruption of a person ability to 
conduct normal life functions, either reported or defined as per clinical 
judgment 
• is a congenital anomaly/birth defect (if exposure to product just before 
conception or during pregnancy resulted in an adverse outcome to the child) 
• is any other important medical event 
• may not result in death, be life-threatening, or require hospitalization, but based 
upon appropriate medical judgment the event may jeopardize the subject or may 
require medical or surgical intervention to prevent one of the outcomes listed in the 
serious definitions above. An important medical event may include development of 
drug dependency or drug abuse. 
 
8.2.3 CLASSIFICATION OF AN ADVERSE EVENT 
 
8.2.3.1 SEVERITY OF EVENT 
 
For adverse events (AEs) not included in the protocol defined grading system, the 
following guidelines will be used to describe severity.  
 
• Mild – Events require minimal or no treatment and do not interfere with the 
participant’s daily activities.  
• Moderate – Events result in a low level of inconvenience or concern with 
the therapeutic measures. Moderate events may cause some interference 
with functioning. 
• Severe – Events interrupt a participant’s usual daily activity and may require 
systemic drug therapy or other treatment. Severe events are usually 
potentially life-threatening or incapacitating.  Of note, the term “severe” 
does not necessarily equate to “serious”. 


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8.2.3.2 RELATIONSHIP TO STUDY INTERVENTION 
 
All adverse events (AEs) must have their relationship to study intervention 
assessed by the clinician who examines and evaluates the participant based on 
temporal relationship and his/her clinical judgment. The degree of certainty about 
causality will be graded using the categories below. In a clinical trial, the study 
product must always be suspect.  
 
• Related – The AE is known to occur with the study intervention, there is a 
reasonable possibility that the study intervention caused the AE, or there is a 
temporal relationship between the study intervention and event. Reasonable 
possibility means that there is evidence to suggest a causal relationship 
between the study intervention and the AE. 
• Not Related – There is not a reasonable possibility that the administration of 
the study intervention caused the event, there is no temporal relationship 
between the study intervention and event onset, or an alternate etiology has 
been established. 
 
 
8.2.3.3 EXPECTEDNESS  
 
The principal investigator will be responsible for determining whether an adverse 
event (AE) is expected or unexpected.  An AE will be considered unexpected if the 
nature, severity, or frequency of the event is not consistent with the risk 
information previously described for the study intervention. 
 
8.2.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT 
AND FOLLOW-UP 
 
 
The occurrence of an adverse event (AE) or serious adverse event (SAE) may 
come to the attention of study personnel during study visits and interviews of a 
study participant presenting for medical care, or upon review by a study monitor. 
 
All AEs including local and systemic reactions not meeting the criteria for SAEs 
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collected includes event description, time of onset, clinician’s assessment of 
severity, relationship to study product (assessed only by those with the training and 
authority to make a diagnosis), and time of resolution/stabilization of the event. All 
AEs occurring while on study must be documented appropriately regardless of 
relationship. All AEs will be followed to adequate resolution. 
 
Any medical condition that is present at the time that the participant is screened 
will be considered as baseline and not reported as an AE. However, if the study 
participant’s condition deteriorates at any time during the study, it will be recorded 
as an AE.  
 
Changes in the severity of an AE will be documented to allow an assessment of the 
duration of the event at each level of severity to be performed. AEs characterized 
as intermittent require documentation of onset and duration of each episode. 
 
The Principal Investigator  will record all reportable events with start dates 
occurring any time after informed consent is obtained until 7 (for non-serious AEs) 
or 30 days (for SAEs) after the last day of study participation.  At each study visit, 
the investigator will inquire about the occurrence of AE/SAEs since the last visit.  
Events will be followed for outcome information until resolution or stabilization. 
 
 
8.2.5 ADVERSE EVENT REPORTING  
An AE is defined as any untoward medical occurrence in a patient or clinical 
investigation subject administered a pharmaceutical product and which does not 
necessarily have to have a causal relationship with this treatment. An AE can, 
therefore, be any unfavorable and unintended sign (e.g., abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal 
product or protocol-specified procedure, whether or not considered related to the 
medicinal product or protocol-specified procedure. Any worsening (i.e., any 
clinically significant adverse change in frequency and/or intensity) of a preexisting 
condition that is temporally associated with the study treatment is also an AE. 
Progression of the cancer under study is not considered an AE.  
All AEs that occur after informed consent form signing must be reported by the 
investigator if they cause the subject to be excluded from the Study or are the result 
of a protocol-specified intervention, including but not limited to washout or 
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AEs will not be collected for subjects during the prescreening period as long as 
that subject has not undergone any protocol-specified procedure or intervention. If 
the subject requires a blood draw, fresh tumor biopsy etc., the subject is first 
required to provide consent to the main study and AEs will be captured according 
to guidelines for standard AE reporting.  
The occurrence of AEs should be sought by non-directive questioning of the patient 
at each study visit. AEs may also be detected when they are volunteered by the 
patient during or between visits or through physical examination, laboratory test, or 
other assessments. As far as possible, each AE should be evaluated to determine: 
 
1. Severity grade (CTCAE Grade 1–4) 
2. Duration (Start and end dates or if continuing at the Safety Follow-up Visit) 
3. Relationship to the study treatment (Reasonable possibility that AE is related: No, 
Yes)  
4. Action taken with respect to study or investigational treatment (none, dose 
adjusted, temporarily interrupted, permanently discontinued, hospitalized, 
unknown, not applicable) 
5. Whether medication or therapy was given (no concomitant medication/non-drug 
therapy, concomitant medication/non-drug therapy) 
6. Outcome (not recovered/not resolved, recovered/resolved, recovering/resolving, 
recovered/resolved with sequelae, fatal, unknown) 
7. Whether it is serious, where a SAE is defined as in this protocol. 
 
All AEs should be treated appropriately. Such treatment may include changes in 
study treatment including possible interruption or discontinuation, starting or 
stopping concomitant treatments, changes in the frequency or nature of assessments, 
hospitalization, or any other medically required intervention. Once an AE is detected, 
it should be followed until its resolution, and assessment should be made at each 
visit (or more frequently, if necessary) of any changes in severity, the suspected 
relationship to the study drug, the interventions required to treat it, and the outcome.  
 
8.2.6 SERIOUS ADVERSE EVENT REPORTING  
 
The study clinician will immediately report to the sponsor any serious adverse 
event, whether or not considered study intervention related, including those listed 
in the protocol or investigator brochure and must include an assessment of whether 


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there is a reasonable possibility that the study intervention caused the event. Study 
endpoints that are serious adverse events (e.g., all-cause mortality) must be 
reported in accordance with the protocol unless there is evidence suggesting a 
causal relationship between the study intervention and the event (e.g., death from 
anaphylaxis). In that case, the investigator must immediately report the event to the 
sponsor. 
 
All serious adverse events (SAEs) will be followed until satisfactory resolution or 
until the site investigator deems the event to be chronic or the participant is stable. 
Other supporting documentation of the event may be requested by the Data 
Coordinating Center (DCC)/study sponsor and should be provided as soon as 
possible. 
 
The Principal Investigator will be responsible for notifying the Food and Drug 
Administration (FDA) of any unexpected fatal or life-threatening suspected 
adverse reaction as soon as possible, but in no case later than 7 calendar days after 
the sponsor's initial receipt of the information.  In addition, the Principal 
Investigator must notify FDA and all participating investigators in an 
Investigational New Drug (IND) safety report of potential serious risks, from 
clinical trials or any other source, as soon as possible, but in no case later than 15 
calendar days after the sponsor determines that the information qualifies for 
reporting. 
 
In case of death, a comprehensive narrative report of the case should be prepared 
by the Investigator together with the SAER. If an autopsy is performed, a copy of 
the autopsy report should be actively sought by the Investigator and sent to the 
Principal Investigator or designee as soon as available. A copy of the autopsy 
report must remain on site with the CRF. 
All deaths will be reported as SAEs regardless of their relationship to disease 
progression and reported via an SAER form from the time of signed informed 
consent until completion of the follow up period. 
A new follow-up SAER form will be filled in by the Investigator if important 
follow-up information (i.e. diagnosis, outcome, causality assessment, results of 
specific investigations) are made available after submission of the initial form. The 
follow up SAER must be signed and dated by the Investigator. The follow-up form 
and any additional source documentation regarding the event will be sent to the 
Principal Investigator, or designee, as described above. 
If a serious medical occurrence or death is reported to the Investigator outside the 
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investigational product, it is the Investigator’s responsibility to report this 
occurrence. 
Such occurrences will be reported using a SAER form or other form of 
communication deemed appropriate by the Investigator. 
 
 
8.2.7 REPORTING EVENTS TO PARTICIPANTS  
If SAEs are seen this study, the informed consent document will be updated with 
pertinent information. 
Participants who had signed previous versions of the informed consent will be 
contacted and asked to sign updated version with new information. 
 
8.2.8 EVENTS OF SPECIAL INTEREST  
Not applicable  
8.2.9 REPORTING OF PREGNANCY  
Not applicable  
 
 
8.3 UNANTICIPATED PROBLEMS 
. 
 
8.3.1 DEFINITION OF UNANTICIPATED PROBLEMS (UP) 
 
 
The Office for Human Research Protections (OHRP) considers unanticipated 
problems involving risks to participants or others to include, in general, any 
incident, experience, or outcome that meets all of the following criteria: 
 
• Unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in the protocol-related documents, such as the 
Institutional Review Board (IRB)-approved research protocol and informed 
consent document; and (b) the characteristics of the participant population 
being studied; 
• Related or possibly related to participation in the research (“possibly 
related” means there is a reasonable possibility that the incident, experience, 
or outcome may have been caused by the procedures involved in the 
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• Suggests that the research places participants or others at a greater risk of 
harm (including physical, psychological, economic, or social harm) than was 
previously known or recognized. 
 
 
8.3.2  UNANTICIPATED PROBLEM REPORTING  
 
The investigator will report unanticipated problems (UPs) to the reviewing 
Institutional Review Board (IRB) and to the Data Coordinating Center (DCC)/lead 
principal investigator (PI). The UP report will include the following information: 
 
• Protocol identifying information: protocol title and number, PI’s name, and 
the IRB project number; 
• A detailed description of the event, incident, experience, or outcome;  
• An explanation of the basis for determining that the event, incident, 
experience, or outcome represents an UP;  
• A description of any changes to the protocol or other corrective actions that 
have been taken or are proposed in response to the UP. 
 
To satisfy the requirement for prompt reporting, UPs will be reported using the 
following timeline:   
 
• UPs that are serious adverse events (SAEs) will be reported to the IRB and 
to the DCC/study sponsor within <insert timeline in accordance with policy> 
of the investigator becoming aware of the event.  
• Any other UP will be reported to the IRB and to the DCC/study sponsor 
within <insert timeline in accordance with policy> of the investigator 
becoming aware of the problem.  
• All UPs should be reported to appropriate institutional officials (as required 
by an institution’s written reporting procedures), the supporting agency head 
(or designee), and the Office for Human Research Protections (OHRP) 
within <insert timeline in accordance with policy> of the IRB’s receipt of 
the report of the problem from the investigator. 
 
 
8.3.3 REPORTING UNANTICIPATED PROBLEMS TO 
PARTICIPANTS  
Not applicable  
 


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9 STATISTICAL CONSIDERATIONS  
 
 
9.1 SAMPLE SIZE DETERMINATION 
 
Sample size for this pilot study was not statistically determined. Instead it was 
decided that up to 80 evaluable study subjects with prostate cancer are sufficient to 
adequately evaluate the tissue distribution of 185±74 MBq (5±2 mCi) 68Ga-
PSMA-11 PET/CT imaging in tumor and non-tumorous regions of the prostate 
and/or pelvic lymph nodes (as determined by histopathology) in patients 
undergoing standard of care prostatectomy and/or pelvic lymph node dissection. 
Further, present calculations from a suitable range of assumptions to gauge the 
robustness of the proposed sample size. 
 
 
 
9.2 POPULATIONS FOR ANALYSES 
 
The enrolled population will consist of all subjects who provided written informed 
consent and received the  dosing of study drug. 
 
9.3 STATISTICAL ANALYSES 
 
9.3.1 GENERAL APPROACH 
 
The detailed prospective procedures for the final data analysis are described in the 
Statistical Analysis Plan (SAP). Any changes in the original statistical 
methodology will be documented in the SAP. Descriptive statistics for all 
continuous variables (N, mean, standard deviation, minimum, median, and 
maximum) or for categorical variables (counts, percentages) will be generated and 
presented as appropriate. 
 
 
 
9.3.2 SAFETY ANALYSES 
 


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The safety data will be summarized for all subjects dosed. Summary tables, 
including change from pre-dose to post-dose where applicable, will be presented 
for the following safety endpoints: 
 
• Vital Signs 
• TEASs 
 
TEAEs will be summarized by the Medical Dictionary for Regulatory Activities 
(MedDRA) body system and preferred term, by intensity, and by causal 
relationship to study agent. 
 
 
 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
 
 
10.1.1 
INFORMED CONSENT PROCESS 
10.1.1.1 
CONSENT/ASSENT AND OTHER INFORMATIONAL 
DOCUMENTS PROVIDED TO PARTICIPANTS 
 
 
Consent forms describing in detail the study intervention, study procedures, and 
risks are given to the participant and written documentation of informed consent is 
required prior to starting intervention/administering study intervention.   
 
 
10.1.1.2 
CONSENT PROCEDURES AND DOCUMENTATION 
 
Informed consent is a process that is initiated prior to the individual’s agreeing to 
participate in the study and continues throughout the individual’s study 
participation. Consent forms will be Institutional Review Board (IRB)-approved 
and the participant will be asked to read and review the document. The investigator 
will explain the research study to the participant and answer any questions that 
may arise. A verbal explanation will be provided in terms suited to the 
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study and of their rights as research participants.  Participants will have the 
opportunity to carefully review the written consent form and ask questions prior to 
signing. The participants should have the opportunity to discuss the study with 
their family or surrogates or think about it prior to agreeing to participate. The 
participant will sign the informed consent document prior to any procedures being 
done specifically for the study. Participants must be informed that participation is 
voluntary and that they may withdraw from the study at any time, without 
prejudice. A copy of the informed consent document will be given to the 
participants for their records. The informed consent process will be conducted and 
documented in the source document (including the date), and the form signed, 
before the participant undergoes any study-specific procedures. The rights and 
welfare of the participants will be protected by emphasizing to them that the 
quality of their medical care will not be adversely affected if they decline to 
participate in this study.  
 
10.1.2 
STUDY DISCONTINUATION AND CLOSURE 
 
This study may be temporarily suspended or prematurely terminated if there is 
sufficient reasonable cause.  Written notification, documenting the reason for study 
suspension or termination, will be provided by the suspending or terminating party 
to <study participants, investigator, funding agency, the Investigational New Drug 
(IND) or Investigational Device Exemption (IDE) sponsor and regulatory 
authorities>.  If the study is prematurely terminated or suspended, the Principal 
Investigator (PI) will promptly inform study participants, the Institutional Review 
Board (IRB), and sponsor and will provide the reason(s) for the termination or 
suspension.  Study participants will be contacted, as applicable, and be informed of 
changes to study visit schedule. 
  
Circumstances that may warrant termination or suspension include, but are not 
limited to: 
• Determination of unexpected, significant, or unacceptable risk to 
participants 
• Demonstration of efficacy that would warrant stopping    
• Insufficient compliance to protocol requirements 
• Data that are not sufficiently complete and/or evaluable 
• Determination that the primary endpoint has been met 
• Determination of futility 
 


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Study may resume once concerns about safety, protocol compliance, and data 
quality are addressed, and satisfy the sponsor, IRB and/or Food and Drug 
Administration (FDA).] 
 
 
 
10.1.3 
CONFIDENTIALITY AND PRIVACY  
 
 
Participant confidentiality and privacy is strictly held in trust by the participating 
investigators, their staff, and the sponsor(s) and their interventions. This 
confidentiality is extended to cover testing of biological samples and genetic tests 
in addition to the clinical information relating to participants. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in 
strict confidence. No information concerning the study or the data will be released 
to any unauthorized third party without prior written approval of the sponsor.  
 
All research activities will be conducted in as private a setting as possible. 
 
The study monitor, other authorized representatives of the sponsor, representatives 
of the Institutional Review Board (IRB), regulatory agencies or pharmaceutical 
company supplying study product may inspect all documents and records required 
to be maintained by the investigator, including but not limited to, medical records 
(office, clinic, or hospital) and pharmacy records for the participants in this study. 
The clinical study site will permit access to such records. 
 
The study participant’s contact information will be securely stored at each clinical 
site for internal use during the study. At the end of the study, all records will 
continue to be kept in a secure location for as long a period as dictated by the 
reviewing IRB, Institutional policies, or sponsor requirements. 
 
Study participant research data, which is for purposes of statistical analysis and 
scientific reporting, will be transmitted to and stored at Houston Methodist 
Department of Urology. This will not include the participant’s contact or 
identifying information. Rather, individual participants and their research data will 
be identified by a unique study identification number. The study data entry and 
study management systems used by clinical sites and by Houston Methodist  
research staff will be secured and password protected. At the end of the study, all 
study databases will be de-identified and archived at Houston Methodist Research 
Institute. 


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10.1.4 
FUTURE USE OF STORED SPECIMENS AND DATA  
 
Data collected for this study will be analyzed and stored at the Houston Methodist,  
Department of Urology. After the study is completed, the de-identified, archived 
data will be transmitted to and stored at the Houston Methodist Research Institute, 
for use by other researchers including those outside of the study.  
 
 
10.1.5 
KEY ROLES AND STUDY GOVERNANCE 
Provide the name and contact information of the Principal Investigator and the 
Medical Monitor. 
Principal Investigator 
Brian Miles, MD 
Houston Methodist Hospital  
6560 Fannin, suite 2100 
Houston, Texas 77030 
713-441-8111 
bjmiles@houstonmethodist.org 
 
 
 
 
 
.  
 
 
10.1.6 
CLINICAL MONITORING 
 
Clinical site monitoring is conducted to ensure that the rights and well-being of 
trial participants are protected, that the reported trial data is accurate, complete, and 
verifiable, and that the conduct of the trial is in compliance with the currently 
approved protocol/amendment(s), with International Conference on Harmonisation 
Good Clinical Practice (ICH GCP), and with applicable regulatory requirement(s).  
 
• Monitoring for this study will be performed by a Research Coordinator from 
the department of Urology at Houston Methodist. 


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• The monitoring will be done on-site, after enrolling the 1st. patient and then 
every 3 months.  
• The monitor will include verification of eligibility criteria, informed consent 
process, adverse events, source data verification (SDV), CRF completion 
and Investigational Product. 
• Other documentation: training, delegation and screening logs. 
• All information will be de-identified for the monitor. 
• The monitor will provide reports that should be filled and forward to QA at 
Houston Methodist. The reports will provide a review of activities, progress, 
and issues of concern. 
 
10.1.7 
QUALITY ASSURANCE AND QUALITY CONTROL 
 
Subject data will be collected on source documents and transcribed on pre-printed 
CRFs provided by the Principal Investigator. The data on each CRF will be legibly 
handwritten with a ballpoint pen or typed. The Principal Investigator or his or her 
authorized designee will sign the CRF on the appropriate page(s) to verify that the 
data on the CRF were reviewed. Records of subjects, source documents, 
monitoring visit logs, data correction forms, CRFs, inventory of study product, 
regulatory documents (e.g., protocol and amendments, IRB/IEC correspondence 
and approvals, approved and signed informed consent forms, Investigator’s 
Agreement, clinical supplies receipts, and distribution and return records), and 
other Principal Investigator correspondence pertaining to the study will be kept in 
the appropriate study files at the site. Source documents include all recordings and 
observations or notations of clinical activities and all reports and records necessary 
for the evaluation and reconstruction of the clinical study. These records will be 
retained in a secure file for the period required by the institution or site policy. 
Quality control (QC) procedures will be implemented beginning with the data 
entry system and data QC checks that will be run on the database will be 
generated. Any missing data or data anomalies will be communicated to the site(s) 
for clarification/resolution. 
 
 
10.1.8 
DATA HANDLING AND RECORD KEEPING  
 
10.1.8.1 
DATA COLLECTION AND MANAGEMENT 
RESPONSIBILITIES  
 


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Data collection is the responsibility of the clinical trial staff at the site under the 
supervision of the site investigator. The investigator is responsible for ensuring the 
accuracy, completeness, legibility, and timeliness of the data reported. 
 
All source documents should be completed in a neat, legible manner to ensure 
accurate interpretation of data.   
 
Hardcopies of the study visit worksheets will be provided for use as source 
document worksheets for recording data for each participant enrolled in the study.  
Data recorded in the electronic case report form (eCRF) derived from source 
documents should be consistent with the data recorded on the source documents.  
 
Clinical data (including adverse events (AEs), concomitant medications, and 
expected adverse reactions data) and clinical laboratory data will be entered into 
Red Cap, a 21 CFR Part 11-compliant data capture system provided by Houston 
Methodist. The data system includes password protection and internal quality 
checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered directly from the source 
documents. 
 
10.1.8.2 
STUDY RECORDS RETENTION  
 
Study documents should be retained for a minimum of 2 years after the last 
approval of a marketing application in an International Conference on 
Harminosation (ICH) region and until there are no pending or contemplated 
marketing applications in an ICH region or until at least 2 years have elapsed since 
the formal discontinuation of clinical development of the study intervention. These 
documents should be retained for a longer period, however, if required by local 
regulations. No records will be destroyed without the written consent of the 
sponsor, if applicable. It is the responsibility of the sponsor to inform the 
investigator when these documents no longer need to be retained. 
 
10.1.9 
PROTOCOL DEVIATIONS  
 
A protocol deviation is any noncompliance with the clinical trial protocol, 
International Conference on Harmonisation Good Clinical Practice (ICH GCP), or 
Manual of Procedures (MOP) requirements. The noncompliance may be either on 
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deviations, corrective actions are to be developed by the site and implemented 
promptly.  
 
These practices are consistent with ICH GCP:  
• 4.5 Compliance with Protocol, sections 4.5.1, 4.5.2, and 4.5.3  
• 5.1 Quality Assurance and Quality Control, section 5.1.1  
• 5.20 Noncompliance, sections 5.20.1, and 5.20.2.  
 
It is the responsibility of the site investigator to use continuous vigilance to identify 
and report deviations within 5 working days of identification of the protocol 
deviation, or within 5 working days of the scheduled protocol-required activity.  
All deviations must be addressed in study source documents, reported to Program 
Official Data Coordinating Center or sponsor.  Protocol deviations must be sent to 
the reviewing Institutional Review Board (IRB) per their policies. The site 
investigator is responsible for knowing and adhering to the reviewing IRB 
requirements.  
 
 
10.1.10 
PUBLICATION AND DATA SHARING POLICY 
 
This study will be conducted in accordance with the following publication and data 
sharing policies and regulations: 
 
National Institutes of Health (NIH) Public Access Policy, which ensures that the 
public has access to the published results of NIH funded research. It requires 
scientists to submit final peer-reviewed journal manuscripts that arise from NIH 
funds to the digital archive PubMed Central upon acceptance for publication. 
 
This study will comply with the NIH Data Sharing Policy and Policy on the 
Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials 
Registration and Results Information Submission rule. As such, this trial will be 
registered at ClinicalTrials.gov, and results information from this trial will be 
submitted to ClinicalTrials.gov. In addition, every attempt will be made to publish 
results in peer-reviewed journals.  Data from this study may be requested from 
other researchers 2 years after the completion of the primary endpoint by 
contacting the Principal Investigator.  
 
 
 


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10.1.11 
CONFLICT OF INTEREST POLICY 
 
The independence of this study from any actual or perceived influence, such as by 
the pharmaceutical industry, is critical.  Therefore, any actual conflict of interest of 
persons who have a role in the design, conduct, analysis, publication, or any aspect 
of this trial will be disclosed and managed. Furthermore, persons who have a 
perceived conflict of interest will be required to have such conflicts managed in a 
way that is appropriate to their participation in the design and conduct of this trial.  
The study leadership in conjunction with Houston Methodist has established 
policies and procedures for all study group members to disclose all conflicts of 
interest and will establish a mechanism for the management of all reported 
dualities of interest. 
 
10.2 ADDITIONAL CONSIDERATIONS 
 
Not applicable  
 
 
 


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10.3 ABBREVIATIONS 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
CFR 
Code of Federal Regulations 
CLIA 
Clinical Laboratory Improvement Amendments 
CMP 
Clinical Monitoring Plan 
COC 
Certificate of Confidentiality 
CONSORT Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
DCC 
Data Coordinating Center 
DHHS 
Department of Health and Human Services 
DSMB 
Data Safety Monitoring Board 
DRE 
Disease-Related Event 
EC 
Ethics Committee 
eCRF 
Electronic Case Report Forms 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act of 2007 
FFR 
Federal Financial Report 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practices 
GWAS 
Genome-Wide Association Studies 
HIPAA 
Health Insurance Portability and Accountability Act  
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonisation  
ICMJE 
International Committee of Medical Journal Editors 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
ISM 
Independent Safety Monitor 
ISO 
International Organization for Standardization 
ITT 
Intention-To-Treat 
LSMEANS Least-squares Means 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
MSDS 
Material Safety Data Sheet 
NCT 
National Clinical Trial 


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NIH  
National Institutes of Health 
NIH IC 
NIH Institute or Center 
OHRP 
Office for Human Research Protections 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SMC 
Safety Monitoring Committee 
SOA 
Schedule of Activities 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
US 
United States 
 
 
 


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10.4 PROTOCOL AMENDMENT HISTORY 
The table below is intended to capture changes of IRB-approved versions of the 
protocol, including a description of the change and rationale. A Summary of 
Changes table for the current amendment is located in the Protocol Title Page.  
 
Version 
Date 
Description of Change  
Brief Rationale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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[6] 
Wachter S, Tomek S, Kurtaran A, Wachter-Gerstner N, Djavan B, Becherer 
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[7] 
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