Clinical trial NCT04086966
Conditions: Metastatic Prostate Cancer
Sponsor: University of Alabama at Birmingham
Start date: 2020-08-20; Completion date: 2022-02-23
Enrollment: 10 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This pilot study will investigate the use of PSMA-PET/MRI (Positron Emission Tomography/ Magnetic Resonance Imaging)to guide radiation treatment planning in patients with known or suspected locally metastatic prostate cancer at the time of diagnosis. Patients will undergo a single PSMA-PET/MRI (or PET/CT (Computed Tomography) in some circumstances) prior to initiation of treatment. Following development of a PSMA-PET guided radiation treatment plan, therapeutic radiation will be delivered per standard-of-care parameters and assessments of feasibility and tolerability will be performed.

Detailed description:

Arms: arm 1: \[68Ga\]PSMA-11 PET/MRI or PET/CT for guiding the radiation treatment plan in patients with known or suspected locally metastatic prostate cancer
Interventions: intervention 1: [68Ga]PSMA-PET/MRI or PET/CT
Intervention descriptions: intervention 1: \[68Ga\]PSMA-PET/MRI or PET/CT

Protocol documents:
Prot_SAP_000.pdf: 
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Official Title: PSMA-PET/MRI for Radiation Treatment Planning in Patients with Locally Metastatic 
Prostate Cancer: A Pilot Study 
 
NCT Number: NCT04086966 
 
Document Date: April 15, 2021 
 
 


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Title: 
PSMA-PET/MRI for Radiation Treatment Planning in Patients with 
Locally Metastatic Prostate Cancer: A Pilot Study 
 
Principal Investigator:      
Samuel J. Galgano, M.D  
 
 
University of Alabama at Birmingham 
 
Department of Radiology 
1824 Sixth Avenue South 
Birmingham, AL  35294-3300 
UAB 
 
 
 
 
 
Tel (205-934-1388); Fax (205-996-0059) 
samuelgalgano@uabmc.edu 
 
Study Supported by:  
             UAB Comprehensive Cancer Center 
 
 
             and Mike Slive Foundation 
 
IRB#: 
 
             300003826 
 
 
Sub-Investigators 
 
 
Affiliation 
 
 
Email:  
 
Andrew McDonald, MD  
 
UAB Radiation Oncology 
ammcdonald@uabmc.edu 
Jonathan McConathy, MD, PhD,  
UAB Radiology  
 
jmcconathy@uabmc.edu 
Kristin Porter, MD, PhD  
 
UAB Radiology  
 
kkporter@uabmc.edu 
Suzanne Lapi, PhD 
 
 
UAB Radiology  
 
lapi@uab.edu 
Denise Jeffers, RPh 
 
 
UAB Radiology  
 
charlottejeffers@uabmc.edu  
 
 
 
Coordinator/Data Managers 
 
April Riddle, R.T. 
 
 
UAB Radiology  
 
ariddle@uabmc.edu  
Sebastian Eady  
 
 
UAB Radiology  
 
smeady@uabmc.edu 
 
Statistical Consultant 
Yufeng Li, PhD  
 
 
UAB Radiology  
 
yli@uabmc.edu  
 
 


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Introduction and Study Rationale 
 
6.0 Overview and Schema 
 
There is great need for more accurate staging of extraprostatic disease at the time of initial diagnosis to 
guide therapy and thereby reduce the rates of biochemical recurrence and death from prostate cancer. 
We propose to develop an optimized simultaneous PET/MRI protocol for local, regional and whole body 
pre-therapeutic initial staging of locally metastatic prostate cancer in a single imaging session using the 
amino acid PET tracer, [68Ga]PSMA-11. Despite advances in the diagnosis and treatment of prostate 
cancer, the pretreatment staging of men with prostate carcinoma (PCa) is currently problematic. 
Conventional imaging is falsely negative for regional lymph node metastases in a substantial fraction of 
men. To address this unmet need, we will determine utility of positron emission tomography (PET) using 
68Ga-labeled PSMA-11 combined with simultaneous PET/MRI (PSMA-PET/MRI) in men with 
oligometastatic prostate cancer to detect regional metastases and plan radiation therapy to boost dose 
to lymph node metastases not identified with CT and/or MRI alone. 
Although not the aim of the current study, this could lead to a 
larger study to evaluate efficacy and outcomes in men undergoing 
PSMA-PET/MRI based radiotherapy planning when compared to 
standard-of-care pelvic radiotherapy. We will compare MRI alone 
to simultaneous PSMA-PET/MRI in terms of lesion detection in 
pelvic nodal stations. Subsequently, patient-specific radiation 
therapy plans will be developed utilizing the results of the PSMA-
PET/MRI and additional radiation will be delivered to suspicious 
pelvic lymph nodes and clinical toxicity will be evaluated to ensure 
no additional adverse events occur due to the additional radiation 
delivered. If this preliminary study suggests a benefit of PSMA-
PET/MRI in the pretreatment setting, additional larger studies will 
be designed based on these results. 
 
This clinical feasibility study will investigate the use of PSMA-
PET/MRI to guide radiation treatment planning and delivery in 
patients with known or suspected locally metastatic prostate 
cancer at the time of diagnosis. The patients will undergo a single 
PSMA-PET/MRI (or PET/CT in some circumstances) prior to 
initiation of treatment. Following development of a PSMA-PET 
guided radiation treatment plan, therapeutic radiation will be 
delivered per standard-of-care parameters and assessments of feasibility and tolerability will be 
performed. A total of 10 patients will be enrolled in this study. If the PET/MRI demonstrates a suspicious 
finding that may make a patient ineligible for radiation therapy, the treating clinician (including urology 
and radiation oncology) will be alerted, and the decision to pursue biopsy and/or alter the patient’s 
treatment plan will be based on standard of care imaging and consensus after presenting the case at the 
GU tumor board. 
 
6.1 Background and Rationale 
 
Prostate cancer will affect approximately one in ten men in their lifetime with approximately 161,360 new 
cases and 26,730 deaths in 2017.[1] Prostate cancer represents approximately 19% of all new cancer cases 
  
Study outline 
Patient with known or 
suspected locally 
metastatic prostate 
cancer at time of 
diagnosis 
Pre-treatment PSMA-
PET/MRI 
Development and delivery 
of PSMA-PET guided 
radiation therapy plan 
SOC assessment for 
radiation side effects 


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in males in the United States with over 3 million men currently living with prostate cancer in the United 
States.[1] There is a substantial minority of patients with high-risk prostate adenocarcinoma that are at 
significant risk for regional nodal and distant metastases at the time of diagnosis.  In contrast to localized 
disease, the 5-year survival for patients with distant metastatic disease is 29%.  
 
There is great need for more accurate staging of extraprostatic disease at the time of initial diagnosis to 
guide therapy and thereby reduce the rates of biochemical recurrence and death from prostate cancer. 
To address this unmet need, we will determine utility of positron emission tomography (PET) using 68Ga -
labeled PSMA-11 combined with simultaneous PET/MRI (PSMA-PET/MRI) in men with oligometastatic 
prostate cancer to detect regional metastases and plan radiation therapy to boost dose to lymph node 
metastases not identified with CT and/or MRI alone. Although not the aim of the current study, this could 
lead to a larger study to evaluate efficacy and outcomes in men undergoing PSMA-PET/MRI based 
radiotherapy planning when compared to standard-of-care pelvic radiotherapy. 
 
The utility of conventional anatomic imaging for staging is limited. Disease control outcomes for men with 
high-risk prostate cancer remain suboptimal, with 10-year biochemical failure rates on the order of 25%-
40% in modern trials of dose-escalated radiotherapy and long-term androgen suppression.[2, 3] 
Additionally, the 5-year disease-free survival rate drops from 85% of patients with no nodal metastases 
to 50% in those patients with nodal metastases. This is thought to be due to lack of detection of small 
volume metastatic disease and small volume locoregionally invasive disease not identified on 
conventional pretreatment imaging.  
 
Prostate MRI is essential for cancer staging within the gland, but limited in detection of nodal metastases. 
While prostate MRI is valuable for the staging of the known cancer, its sensitivity and specificity for the 
detection of pelvic lymph node metastases is limited by RECIST 1.1 criteria and nodal morphology. 
Molecular imaging has great potential to supplement MRI and increase diagnostic accuracy, and 
simultaneous PET/MRI can provide both dedicated pelvic PET and MRI imaging for regional staging as well 
as whole body staging in a single imaging session.  
 
PSMA PET ligands show great promise for detection of both intraprostatic and extraprostatic disease. 
Prostate specific membrane antigen (PSMA) is a transmembrane cellular receptor that is overexpressed 
in prostate cancer cells. Recently, small molecules have been developed that bind to the extracellular 
component of the transmembrane PSMA receptor. These agents have been tagged with both 18F and 68Ga 
for imaging and 90Y and 177Lu for therapeutic purposes. Restaging accuracy of fluciclovine and PSMA-
PET/CT are superior to choline compounds, particularly at low PSA levels, and a single 10 patient case 
series suggests superiority of PSMA PET over fluciclovine.[4, 5]  A limitation of PSMA ligands is that 
approximately 10% of prostate carcinoma and nodal metastases are PSMA negative.1-4  
 
PET imaging has been shown to alter radiation treatment planning in patients with recurrent prostate 
cancer. The concept of PET guided radiation therapy is well-established and utilizes standardized uptake 
values (SUV) within lesions to automatically segment target volumes.[6-8] The technique has been 
evaluated previously in recurrent prostate cancer with use of [11C]choline and [18F]fluorocholine PET/CT 
with increases in detected gross tumor volume.[9, 10] PSMA-PET/CT has been demonstrated to be 
superior to [11C]choline PET/CT in recurrent prostate cancer in both sensitivity and specificity and has 
been shown to alter radiation therapy management in a substantial fraction of patients.[11-14] Therefore, 
we expect that PSMA-PET/MRI will be valuable in the initial staging and radiation treatment planning in 
patients with oligometastatic prostate cancer and that target lesion segmentation is feasible utilizing SUV 
thresholding. 


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PET/MRI is likely the optimal modality to image patients for pretreatment staging of prostate carcinoma. 
In one study, a patient can undergo a multiparametric prostate MRI for characterization of the primary 
lesion and the extent of regional extraprostatic disease along with a molecular imaging study to improve 
the accuracy of regional staging and provide whole body staging. In addition, simultaneous acquisition of 
PET and MRI data allows for more accurate coregistration of MRI and PET data which may be difficult to 
achieve with software fusion, a key to detecting non-enlarged lymph nodes and other small lesions. 
 
6.2 Study Objectives 
 
Specific Aim #1: Determine the concordance of imaging findings for PSMA-PET/MRI and MRI of the pelvis 
and prostate gland. 
 
Hypothesis #1: PSMA-PET/MRI will identify more regional lymph node metastases than MRI alone.  
 
There have been numerous prior studies demonstrating the value of MRI for the locoregional staging for 
PCa. We expect the simultaneous acquisition of MRI and PSMA PET data to provide valuable preoperative 
staging information, with PSMA PET detecting metastatic disease in subcentimeter pelvic lymph nodes 
not identified with MRI alone. Additionally, PSMA-PET/MRI provides whole body staging in regions not 
evaluated by pelvic MRI and may detect additional distant metastases. 
 
Specific Aim #2: Establish feasibility and assess acute toxicity of PSMA-PET/MRI directed pelvic 
radiotherapy. 
 
Hypothesis #2: PSMA-PET/MRI directed radiation therapy will be feasible in the vast majority of patients 
(>90%) and can be safely administered without increased acute radiation toxicities.  
 
The primary goal of Specific Aim 2 is to provide preliminary information to confirm the feasibility of 
radiation dose escalation to the suspicious LNs identified on PSMA-PET/MRI. If results from this trial are 
supportive, this will lead to a larger clinical trial evaluating efficacy and disease outcomes between 
patients who have undergone PSMA-PET/MRI directed radiotherapy versus standard-of-care pelvic 
radiotherapy. 
 
6.3 Investigational Plan 
 
6.3.1 
Study Design 
 
Prospective IRB-approved study enrolling 10 patients with locally metastatic prostate cancer for 
pretreatment PSMA-PET/MRI prior to the initiation of treatment  
 
All patients will undergo standard-of-care clinical evaluation and imaging workup with nuclear 
medicine bone scan and either CT of the abdomen and pelvis or MRI pelvis 
 
Patients will undergo standard-of-care androgen deprivation therapy following PSMA-PET/MRI 
and prior to radiation therapy 
 
If study PET/MRI demonstrates a suspicious finding that may preclude a patient radiation 
therapy, the treatment team will be alerted to potentially investigate the finding further (i.e. 
additional imaging or biopsy) 
 
Acute radiation toxicities will be assessed at standard-of-care intervals 
 


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6.3.2 
Study Population 
 
Men with treatment-naïve prostate cancer with metastatic disease localized to the pelvis 
 
6.3.3 
Inclusion Criteria 
 
Biopsy-proven treatment-naïve prostate adenocarcinoma with pelvic metastases known to 
suspected on standard-of-care staging imaging or a nomogram-based risk of lymph node 
metastases greater than or equal to 20% 
 
Eligibility and plan to undergo definitive radiation therapy for prostate cancer per established 
standard-of-care radiation oncology clinical guidelines 
 
Be at least 18 years of age. 
 
6.3.4 
Exclusion Criteria 
 
Inability to tolerate or undergo PET/MRI or PET/CT 
 
Previous or current hematologic or lymphatic disorder (including leukemia, lymphoma, 
Castleman’s disease, etc.) 
 
Recurrent prostate adenocarcinoma 
 
Known distant metastatic disease 
 
Current or prior treatment for prostate cancer 
 
6.3.5 
Withdrawal Criteria 
 
Given that enrollment in this study will involve a single imaging exam, no withdrawal criteria will 
be used 
 
6.3.6 
Replacement of Patients 
 
Given that enrollment in this study will involve a single imaging exam, no replacement of 
patients will be used 
 
6.3.7 
Study Duration 
 
Study enrollment and imaging will take place over 24 months 
 
6.3.8 
Safety Monitoring 
 
6.3.8.1 Data and Safety Monitoring Plan 
 
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. PET/MRI scans will be loaded into a 
separate password-protected image storage system that will not appear on the PACS utilized in 
clinical practice.  
 
6.3.9 
Ethical Considerations 
 
Given that the study involves a single imaging session with PET/MRI and the expected age of the 
enrolled adult patients, ethical concerns regarding additional radiation exposure are minimal. 


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The only ethical consideration was the availability of the results of the study PET/MRI to the 
clinicians. Although the PET radiopharmaceutical used ([68Ga]PSMA-11) is not currently FDA-
approved, it has been extensively studied and used in Europe with excellent correlation 
between radiotracer activity and metastatic disease. Therefore, a suspicious lesion on the study 
PET/MRI is expected to correlate with metastatic disease. Therefore, if the PET/MRI 
demonstrates a suspicious finding, the treating clinician (including urology and radiation 
oncology) will be alerted, and the decision to pursue biopsy and/or alter the patients treatment 
plan will be based on standard of care imaging and consensus after presenting the case at the 
GU tumor board.  
 
6.4 Study Procedures 
 
6.4.1 
Informed Consent Procedure 
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 IRB-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.  
6.4.2 
Patient Registration 
Enrollment in the study will be available after the patient has been seen by their treating physician 
at UAB. The majority of these patients are expected to be seen by Radiation Oncology in either their 
own clinic or as part of multidisciplinary Urology clinic. However, all patients that meet enrollment 
criteria are eligible. Registration in the study will be performed by a research coordinator from the 
UAB Department of Radiology. Participation in the study is voluntary and choosing not to participate 
will not affect patient care in any way. 
 
6.4.3 
Initiation of Study 
The PET tracer [68Ga]PSMA-11 is made on site in the UAB Radiopharmacy by a licensed 
Radiopharmacist. [68Ga]PSMA-11 is an investigational new drug (IND) and the study will be initiated 
only after approval of UAB Radiation Safety Committee, UAB IRB and FDA.  
 
6.4.4 
Drug Information 
[68Ga]PSMA-11 is an investigational PET radiopharmaceutical that has been used extensively in 
clinical trials for patients with newly diagnosed and biochemically recurrent prostate cancer. The 
radiopharmaceutical targets the PSMA transmembrane protein, which is overexpressed in prostate 
cancer cells. The target dosage of radiopharmaceutical administered to the patient is 185 MBq (5 
mCi) ±10% given intravenously. This results in an effective dose of approximately 3 mSv to the 
patient, which is equal to 1 years of natural background radiation exposure (3 mSv/yr).  
 
6.4.5 
Patient Assessment 
Identification and workup of patients prior to potential enrollment in the study will follow standard-
of-care procedures per the treating physician (urology, radiation oncology, etc.). For initial staging of 
prostate cancer, this will include a nuclear medicine bone scan and either a CT abdomen and pelvis 
or MRI of the pelvis per NCCN guidelines. If a patient is determined to be eligible for the study, the 
research coordinator in this study will be asked to come to the clinic to discuss potential enrollment 
in the study. 
 


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6.4.6 
Imaging Information 
 
6.4.6.1 [68Ga]PSMA-11 PET Preparation and Injection 
The injected dose of PSMA will be 185 MBq (5 mCi) followed by an uptake interval of 50-100 
minutes.5 The patient will be instructed to avoid strenuous exercise for 24 hours prior to 
injection and to avoid caloric intake for 4 hours prior to injection.  
 
6.4.6.2 [68Ga]PSMA-11 PET/MRI  and PET/CT Protocol 
 
Whole body imaging 
Positron Emission Tomography Acquisition: The patient will be placed on the PET/MRI scanner 
in the supine position. Initial localizer images will be obtained. Subsequently, static whole body 
images will be acquired from pelvis to skull base utilizing approximately eight 14 cm detector beds 
for 5 minute acquisitions per bed position. Correction for randoms, scatter, attenuation and 
reconstructions will be performed per the manufacturer’s recommendations.  
 
Whole Body MRI: Sequences performed will include MR attenuation correction (MRAC), axial and 
coronal T2 single shot fast spin echo, sagittal T1 turbo spin echo for skeletal evaluation, and whole 
body Dixon-derived sequences. 
 
Following whole body PET imaging, a routine noncontrast MRI of the prostate gland will be 
performed at UAB in the PET/MRI scanner per institutional protocol, which includes high b-value 
diffusion-weighted imaging (b2000) and small field-of-view T2 imaging. Dynamic-contrast 
enhanced and post-contrast T1 images will be omitted from the protocol to reduce scan time and 
due to less impact on scan interpretation for patients presenting for staging of known prostate 
cancer. An additional static pelvic PET acquisition will be performed concurrently. 
 
PET/CT Acquisition: If a patient is unable to undergo PET/MRI secondary to technical failure of 
the PET/MRI scanner, MRI-incompatible metallic implant, or severe claustrophobia, a PET/CT 
may be performed instead at the Primary Investigator’s discretion. The patient will be placed on 
the PET/CT scanner in the supine position. Initial localizer images will be obtained. 
Subsequently, static whole body images will be acquired from pelvis to skull base utilizing 
approximately eight 14 cm detector beds for 5 minute acquisitions per bed position. Correction 
for randoms, scatter, attenuation and reconstructions will be performed per the manufacturer’s 
recommendations. 
 
6.4.6.3 PET/MRI Imaging Interpretation and Storage 
Images from the PET/MRI will be stored and reviewed using a commercially available software 
package (MIM Encore, Cleveland, OH) and not be available for viewing in the institutional PACS 
or patient’s medical record. This is in an effort to blind the treating physicians from making 
clinical decisions on an experimental imaging technique. The prostate MRI images will be sent to 
clinical PACS and the medical record as part of standard-of-care imaging and can be used in the 
clinical-decision making process. No formal interpretation will be generated for the [68Ga]PSMA-
PET portion of the PET/MRI study, but the prostate MRI will have a clinical interpretation by a 
dedicated abdominal radiologist who will also be blinded to the patient enrollment in the study. 
Dedicated study readers from both abdominal imaging and molecular imaging will interpret first 
the prostate MRI alone, and then the fused PET/MRI to assess potential added value from the 
PET/MRI. The study readers will be blinded to the results of any additional standard-of-care 


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imaging and clinical evaluation and will only have knowledge that the patient has biopsy-proven 
prostate cancer. 
 
Assessment of the prostate MR primary lesion location, extracapsular extension (ECE), seminal 
vesicle invasion (SVI), and metastatic disease will be evaluated utilizing a Likert scale from 1-5 to 
indicate reader confidence utilizing PI-RADS v2.0 criteria. The PSMA-PET/MRI will be evaluated 
with the same 1-5 Likert scale utilizing the PSMA-RADS v1.0 criteria.[16]  The number of pelvic 
nodal metastases detected at each lymph node station will be recorded. Exams will be interpreted 
by three radiologists/nuclear medicine physicians to evaluate interreader agreement with 
disputes resolved by consensus. 
 
MRI Data Analysis: The MRI images will be qualitatively analyzed. 
 
Qualitative analysis: A visual evaluation of the pelvic lymph nodes with suspected metastatic 
disease will be performed. The number of positive metastatic lymph nodes and their nodal 
stations will be recorded. Nodal stations that will be examined include right and left common iliac, 
internal iliac, external iliac, obturator, inguinal, and retroperitoneal (total of 11 stations per 
patients). 
 
MRI Images 
1 = Normal lymph nodes 
2 = Mild prominence not meeting RECIST criteria for adenopathy (low suspicion) 
3 = Borderline enlarged by RECIST criteria (intermediate suspicion) 
4 = Definitely abnormal size or morphology, probable metastasis (high suspicion) 
5 = Markedly abnormal size and morphology, definite metastasis (very high suspicion) 
 
Note: In cases of nonhomogenous intensity on MRI images, the grade will be determined on the 
basis of the most suspicious area.  
 
PET Data Analysis: The PET images will be qualitatively and quantitatively assessed. The scoring 
will be based primarily on the PET data, but the reader will have access to the MRI data for 
anatomic correlation and characterization of lymph node morphology. For PET data analysis, a 
lymph node positive based on MRI criteria but negative based on PSMA-PET criteria will be scored 
as negative. 
 
Qualitative analysis: A visual evaluation of the pelvic lymph nodes with suspected metastatic 
disease will be performed utilizing PSMA-RADS version 1.0 criteria (Table 1). The number of 
positive metastatic lymph nodes and their nodal stations will be recorded. 
 
Quantitative analysis: Nodes scored as intermediate or higher suspicion based on MRI and/or 
PET will undergo further quantitative analysis.  
 
Standardized uptake values (SUVs): The maximum SUV will be measured. Additionally, the 
mean SUV and metabolic tumor volume will be measured based on a 40% isocontour.   
 
 
TABLE 1 


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Summary of PSMA-RADS Version 1.0 for Reporting Findings on PSMA-Targeted PET Imaging 
Category 
Findings 
PSMA-RADS-1 (benign) 
PSMA-RADS-1A 
 
Benign lesion characterized by biopsy or pathognomonic finding on anatomic imaging 
and without abnormal uptake. 
PSMA-RADS-1B 
 
Benign lesion characterized by biopsy or pathognomonic finding on anatomic imaging 
and with focal radiotracer uptake. 
PSMA-RADS-2 
(likely benign) 
 
 
Equivocal (focal, but low level such as blood pool) uptake in soft-tissue site atypical of 
PCa involvement (e.g., axillary or hilar lymph nodes); equivocal uptake in bone lesion 
atypical of PCa involvement (e.g., uptake fused to bone lesion and strongly suspected 
of being degenerative or another benign etiology. 
PSMA-RADS-3 (equivocal*) 
PSMA-RADS-3A 
 
 
 
 
Equivocal uptake in soft-tissue site typical of PCa involvement (e.g., pelvic or 
retroperitoneal lymph nodes). If targetable for biopsy (up to and including excision), 
biopsy may help confirm diagnosis. Alternatively, follow-up imaging (either anatomic 
or PSMA-targeted PET/CT) showing progression can confirm diagnosis. We 
recommend initial follow-up period of 3–6 mo. 
PSMA-RADS-3B 
 
 
 
 
 
Equivocal uptake in bone lesion not definitive but also not atypical of PCa on 
anatomic imaging (i.e., pure marrow-based lesion with little if any surrounding bony 
reaction, lytic or infiltrative lesion, or classic osteoblastic lesion). Comparison to bone 
scan, Na18F PET, or tumor-protocol MR images may be helpful, and bone biopsy may 
have a role. Alternatively, follow-up imaging (either anatomic or PSMA-targeted 
PET/CT) with evidence of progression may confirm diagnosis. We recommend initial 
follow-up period of 3–6 mo. 
PSMA-RADS-3C 
 
 
 
 
Intense uptake in site highly atypical of all but advanced stages of PCa. Likelihood of 
nonprostatic malignancy or other benign tumor is high. Biopsy to confirm diagnosis 
histologically is often preferred, although organ-specific follow-up imaging may be 
done (e.g., liver-protocol MRI to evaluate possible primary hepatocellular 
carcinoma). 
PSMA-RADS-3D 
 
 
 
 
Lesion suggestive of malignancy on anatomic imaging but lacking uptake. Differential 
considerations include nonprostatic malignancy, neuroendocrine PCa, and an 
uncommon case of prostate adenocarcinoma that fails to express PSMA. Biopsy to 
confirm diagnosis histologically is often preferred, although organ-specific follow-up 
imaging may be done. 
PSMA-RADS-4 
(PCa highly 
likely) 
 
Intense uptake in site typical of PCa but lacking definitive findings on conventional 
imaging. Given the high specificity of PSMA agents in all reported series, it is unlikely 
that biopsy confirmation will be needed, although obtaining tissue for genomic 
analysis or other purposes may be useful. 
PSMA-RADS-5 
(PCa almost 
certainly 
present) 
Intense uptake in site typical of PCa and having corresponding findings on 
conventional imaging. Given the high specificity of PSMA agents in all reported 
series, it is unlikely that biopsy confirmation will be needed, although obtaining 
tissue for genomic analysis or other purposes may be useful. 
 


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6.4.7 
Safety Monitoring 
Vital signs will be assessed immediately before and after injection of [ 68Ga] PSMA-11 (HR and supine 
BP).  Patients will be monitored for adverse events during injection and after completion of the 
imaging study. Additionally, patient’s vitals (HR and supine BP) will be checked at the completion of 
the imaging study prior to leaving the imaging center. 
 
6.4.8 
Patient Follow-Up 
Patients will be called within 24 hours of [68Ga]PSMA-11 administration to ensure no adverse events 
have occurred.  Patients will be seen in the clinic if there are any concerning study related adverse 
events requiring further evaluation. 
 
6.5 
Radiation Treatment Planning and Delivery 
 
6.5.1 
RADIOTHERAPY SIMULATION 
CT simulation for radiotherapy planning will be performed within 8 weeks of the initiation of 
neoadjuvant androgen suppression (per standard-of-care clinical guidelines) and within 10 weeks of 
the PSMA staging scan. Patients will be asked to have an empty rectum and full bladder at time of 
simulation. Bowel regimen will consist of two 17g doses of polyethylene glycol laxative and two 125mg 
doses of simethicone the day prior to simulation. Patients will be asked to drink 24 ounces of water 
30 minutes prior to simulation in order to ensure bladder fullness. A custom molded foam form will 
be created to aid patient immobilization. A retrograde urethrogram will be performed to improve 
visualization of the prostate apex 6. The CT scan will extend from the L1/L2 to mid-femur and will 
utilize ≤3mm slice thickness. Intravenous iohexol contrast will be utilized to improve visualization of 
lymph nodes. All CT simulation parameters and patient preparation is per standard-of-care clinical 
guidelines. 
 
6.5.2 RADIOTHERAPY TARGET VOLUME DELINEATION (Figure 1) 
 
Varian Eclipse software (Varian Medical Systems LLC, Palo Alto, CA, USA) will be used for radiotherapy 
target delineation and treatment planning. For all patients we will initially define traditional standard-
of-care clinical target volumes for the treatment of high risk prostate cancer: 
 
CTVP+SV will contain the entire prostate gland and portion of the seminal vesicles at risk for tumor 
involvement. At least the proximal 1cm of the seminal vesicles. In cases where gross seminal vesicle 
invasion is identified the entire seminal vesicles will be included. 
CTVeLN will contain the elective lymph node target volumes. Elective nodal regions will be delineated 
in accordance with published consensus guidelines7 and will include the obturator, internal iliac, 
external iliac, and distal common iliac chains. 


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Next, the PSMA PET scan will be rigidly co-registered to radiation simulation CT scan. Rigid co-
registration is preferred for two specific reasons: (1) we recognize that 8-10 weeks of androgen 
suppression between PSMA-PET/MRI and radiotherapy simulation may lead to in changes in LN size 
that may lead to error in deformable registration, and (2) prior experience with PSMA-PET/MRI co-
registration in the biochemical recurrence setting indicates that rigid co-registration results in good 
anatomic agreement in the majority of cases8. Using the registered PSMA-PET/MRI we will delineate 
an additional CTV: 
 
CTVLN BOOST will contain LNs with maximum SUV greater than 1.3 times the blood pool reference. The 
LNs will be segmented on the MRI portion of the PSMA-PET/MRI and superimposed on the co-
registered CT simulation scan. The resulting structure will be edited to create CTV LN BOOST by excluding 
bowel structures and barriers to tumor spread (e.g. muscle or bone). We note that suspicious LNs are 
likely to be smaller on the CT simulation scan due to the initiation of androgen suppression, but CTV LN 
BOOST will not be further reduced so as to account for potential microscopic tumor extension. This 
concept is analogous to involved node radiotherapy utilized for post-chemotherapy consolidation of 
lymphoma9.  
 
Planning target volume (PTV) expansions for CTVP+SV will be 4mm posteriorly and 7mm in all other 
directions. PTV expansions for CTVeLN and CTVLN BOOST will be 8mm in all directions.  
 
6.5.3 RADIOTHERAPY TREATMENT PLANNING AND DELIVERY 
We will utilize a moderately hypofractionated dose regimen which is standard-of-care at our 
institution. Our institutional technique for elective pelvic irradiation with a simultaneous integrated 
boost to the prostate and proximal seminal vesicles has been described in multiple peer-reviewed 
publications10-13 and moderate hypofractionation is recognized by the National Comprehensive 
Cancer Network as an appropriate dose regimen for men with high-risk and node positive prostate 
cancer14. We will prescribe 70 Gy to PTVP+SV, 60.2 Gy to PTVLN BOOST, and 50.4 Gy to PTVeLN 
Figure 1: Example of fluciclovine-PET/MRI directed radiotherapy treatment planning.  Left image 
shows the [
18F]fluciclovine PET-MRI with lower window of PET window set to 1.3 times blood 
pool. The suspicious LN is segmented in red. Right image is the treatment planning CT for the 
same patient with CTVLN BOOST delineated in green and the associated PTV in blue. 


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simultaneously in 28 fractions of 2.5 Gy, 2.15 Gy, and 1.8 Gy, respectively. Treatment plans will be 
generated to meet the criteria specified in Table 2. The prescription to PTVLN BOOST may be escalated 
beyond 60.2 Gy at the discretion of the treating radiation oncologist if all organ-at-risk constraints are 
met, but will not be allowed to exceed 70 Gy. Treatment plans will utilize either intensity modulated 
radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT). Daily image guidance will be 
performed utilizing cone beam CT performed prior to the delivery of each fraction and emphasis of 
patient alignment will be at the prostate-rectum interface.  
 
Table 2: Pre-specified dosimetric criteria for plan acceptability. 
Structure 
Dosimetric Parameter 
Per Protocol 
Variation 
Acceptable 
PTVP+SV 
V70 Gy[%] 
≥95% 
≥90% 
  
Maximum dose 
<75 Gy 
<77 Gy 
PTVLN BOOST 
V60.2 Gy[%] 
≥90% 
-1 
  
Maximum dose 
<66 Gy 
<68 Gy 
PTVeLN 
V50.4 Gy[%] 
≥95% 
≥90% 
  
Maximum dose 
<55 Gy 
<58 Gy 
Rectum 
V70 Gy[cc] 
<3cc 
<5cc 
  
V60 Gy[%] 
<10% 
<15% 
  
V50 Gy[%] 
<25% 
<40% 
Small bowel 
Maximum dose 
<54 Gy 
<58 Gy 
  
V54 Gy[cc] 
0cc 
<20cc 
  
V45 Gy[cc] 
<120cc 
Not specified 
Bladder 
V60 Gy[%] 
<20% 
<25% 
  
V40 Gy[%] 
<50% 
<60% 
Femoral heads 
V50 Gy[%] 
<5% 
<10% 
1No minimum acceptable coverage of PTVLN BOOST is specified due to potential overlap 
between the target volume and bowel structures is may occur. In such instances effort 
should be made to ensure CTVLN BOOST V60.2 Gy[%] ≥ 90%.  
 
6.5.4 RADIOTHERAPY ASSESSMENTS 
 
Clinical toxicity during and after radiation therapy will be scored using the Common Terminology 
Criteria for Adverse Events version 5.0 (CTCAE v5.0). Response to therapy will be assessed with 
interval PSA measurement. All of these measures will be assessed per standard-of-care intervals for 
all patients undergoing radiation therapy for prostate cancer. We will utilize a battery of validated 
measures: 
 
 
 
 
 
 


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†Performed as part of clinical care 
 
6.5.5 Study Variables and Key Endpoints 
For specific aim 1, we will assess the concordance between prostate MRI and PSMA-PET/MRI for the 
detection of seminal vesicle invasion and pelvic metastatic disease. The total number of pelvic nodal 
metastases detected on MRI and PSMA-PET/MRI will be compared. The confidence in detection of 
seminal vesicle invasion on a 0-3 Likert scale will also be compared between MRI and PSMA-PET/MRI. 
The primary endpoint for specific aim 1 number of patients who demonstrate pelvic LN metastases 
on PSMA-PET/MRI that were not detected on conventional anatomic imaging. We expect at least 25% 
of patients to demonstrate pelvic LN metastases that were not detected on conventional anatomic 
imaging. 
 
For specific aim 2, study participants who remain eligible for pelvic radiation therapy (e.g. no distant 
metastases) will be subdivided into two cohorts: those without suspicious extraprostatic activity on 
PSMA-PET/MRI and those whose PSMA-PET/MRI demonstrates suspected seminal vesicle invasion 
and/or pelvic nodal metastatic disease. Those without suspicious extraprostatic uptake will undergo 
standard-of-care radiation therapy. Patients with positive PSMA-PET/MRI scans will undergo radiation 
treatment planning with a boost given to the suspicious lesions. The primary endpoint of specific aim 
2 is to assess the number of patients with positive PSMA-PET/MRI scans where the radiation boost is 
feasible. We expect that the radiation treatment planning will be feasible in at least 90% of patients 
with positive PSMA-PET/MRI scans. A secondary endpoint is to compare the frequency of acute 
radiation toxicities between the cohorts. We expect that less than 15% of patients who undergo 
PSMA-PET/MRI directed LN radiotherapy boost will experience CTCAE v5.0 grade 3+ genitourinary or 
gastrointestinal toxicities and that no patient will experience a grade 5 genitourinary or 
gastrointestinal toxicity. All grade 3 toxicities will be reviewed by the radiation oncology sub-
investigator.  If any grade 4 or 5 events occur, the cases will be reviewed among members of the study 
team and the study will potentially be paused/terminated if there is concern that deviation from 
standard of care radiation therapy has caused undue harm to the patient. 
 
6.5.6 Study Termination 
The study will stop enrolling patients once the target number has been reached. 
 
6.6 Statistical Considerations 
6.6.1  Study Design and Sample Size Calculation 
Table 3:  Study Calendar. 
 
Pre-Study 
Imaging Visit - 
1-2 weeks before 
radio-therapy 
As part of clinical care 
H&P 
X 
 
X 
PSMA-11 
PET-MRI 
 
X 
 
PSA† 
 
 
X 
CTCAE Toxicity 
Assessment† 
 
 
X 


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Given the pilot nature of this study and small sample size, no formal power or sample size 
calculations were performed.  
 
6.6.2 
Definition of Analyzed Study Population 
Study population is adult males with treatment-naïve prostate adenocarcinoma who meet the 
inclusion criteria listed above. 
 
6.6.3 
Analysis 
Demographic and clinical characteristics of all the enrolled patients will be summarized using 
descriptive and graphical statistics. Mean and standard deviation will be provided for continuous 
variable and counts and percentage will be for categorical variables.  To ensure the quality of 
imaging data, imaging data from three readers will be assessed first using Kappa statistics (K) for 
inter-rater agreement.   
 
For the primary analysis in Aim 1, the number of patients who are identified with lymph node 
metastases (positive nodal) will be counted, and percentage and 95% exact confidence interval will 
be calculated using the Clopper-Pearson method for PSMA-PET/MRI and MRI respectively. 
Concordance and agreement between two methods will be evaluated using Cohen's kappa statistic, 
κ. For the primary analysis in Aim 2, SUV thresholding, CTV, and other imaging parameters between 
PSMA-PET/MRI and MRI will be determined using the Bland-Altman plot analysis in addition to 
descriptive analysis. Safety analysis of acute radiation toxicities related AE/SAE in Aim 2 will be 
descriptive, such as frequency and percentage will be reported.  We will also report the frequency of 
patients with any grade 3 GI or GU toxicity, and any grade 4-5 toxicity. All statistical analysis will be 
carried out using the Statistical Analysis Software SAS v 9.4. 
 
 
6.7 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. 
6.7.1 
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 
UAB IRB. Prior to obtaining IRB approval, the protocol must be approved by the by the UAB 
Comprehensive Cancer Center Protocol Review Committee (PRC).  The initial protocol and all 
protocol amendments must be approved by the IRB prior to implementation.   
6.7.2 
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 IRB-approved informed consent form prior to participation in any study specific procedure.  The 


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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.  
6.7.3 
Changes in the Protocol 
Once the protocol has been approved by the UAB IRB and FDA, any changes to the protocol must be 
documented in the form of an amendment, submitted to and approved by both IRB and FDA.   
 
If it becomes necessary to alter the protocol to eliminate an immediate hazard to patients, an 
amendment may be implemented prior to IRB approval.  In this circumstance, however, the 
Investigator must then notify the IRB in writing within five (5) working days after implementation.   
6.8 Adverse Event Reporting 
As with many IV administered agents, [68Ga]PSMA-11 could cause an allergic reaction that could 
potentially pose a threat to life (anaphylaxis).  This has not been observed in limited human exposure to 
date.  Reasonable precautions should be taken, consistent with normal radiologic and clinical facility 
practice.  The patient should be monitored until the PET procedure is completed, and trained personnel 
and emergency equipment should be available per facility standards. 
 
Qualifying Adverse Events (AEs), including Serious Adverse Events (SAEs), as defined herein, will be 
reported via the FDA Adverse Event Expedited Reporting System (AERS). For the [68Ga]PSMA IND we will 
report adverse events based on the FDA final rule for IND safety reporting requirements under 21 CFR 
part 312 published on September 29, 2010 and implemented on March 28, 2011.  This investigational 
study is not a BA or BE study so 21 CFR part 320 is not applicable.  Adverse events will also be reported 
to the UAB IRB according to their requirements. 
 
6.8.1 
General Definitions (from 21 CFR 312.32 (a)) 
Adverse Event (AE): An Adverse Event is an untoward medical occurrence associated with the use of 
the drug in humans, whether or not considered drug related. For this study, the drug is [68Ga]PSMA 
and adverse events would include any events experienced by a study participant during the Adverse 
Event reporting period defined in Table 1 whether or not it was considered to be related to the 
[68Ga]PSMA.   At the conclusion of the imaging study, the imaging technologist will observe the 
patient and also inquire if they are back to their usual state of health.  If a negative answer is 
received, then the physician will be called to investigate this report as a possible adverse reaction. 
 
Adverse Reaction:  An Adverse Reaction is any adverse event caused by a drug. In this study, the 
drug is [68Ga]PSMA. 
 
Suspected adverse reaction means any adverse event for which there is a reasonable possibility that 
the IND drug caused the adverse event.  For the purposes of IND safety reporting, “reasonable 
possibility” means 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 adverse reaction, which means any adverse event caused by a drug. 
 
An adverse event or suspected adverse reaction is considered “unexpected” if it is not listed in the 
investigator brochure 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. 
 


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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, a 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 functions, or a congenital 
anomaly/birth defect. Important medical events that may not result in death, be 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. 
 
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. 
 
Investigational Agent:  An investigational agent is any agent held under an Investigational New Drug 
(IND) application.  For purposes of this study, [68Ga]PSMA is the investigational agent. 
 
6.8.2 
AE Reporting Requirements 
The investigators on this protocol will report any suspected adverse events that occur after 
[68Ga]PSMA administration and within the specified follow-up period to Dr. Galgano and they will 
work together to determine whether there was an adverse event or adverse reaction and the 
severity of the adverse event or reaction. 
 
All AEs will be followed by the investigators until resolution, stabilization, scientifically and clinically 
satisfactory explanation as to attribution and etiology is achieved, or until subject is lost to follow 
up.   
 
6.8.2.1 CAEPR/ASAE for [68Ga]PSMA 
The Comprehensive Adverse Event and Potential Risks list (CAEPR) provides a single list of 
reported and/or potential adverse events (AE) associated with an agent using a uniform 
presentation of events by body system. The Agent Specific Adverse Event List (ASAEL) would 
include the expected adverse events associated with the use of [ 68Ga]PSMA. At this time, there 
have rare reported AEs associated with the use of a [68Ga]PSMA in clinical studies (≤1% of 
patients). The most common adverse reactions were injection site pain and injection site 
erythema. We will continue to update our CAEPR and ASAE lists as this study progresses, 
including by reviewing the literature and our in-house data safety monitoring.  If any are found, 
we will begin an ASAE list.  Any information on reported AEs for [ 68Ga]PSMA will be provided by 
the sponsor to all of the investigators on this protocol. 
 
6.8.2.2 Potential but Unexpected AE for [68Ga]PSMA 
There have rare reported AEs associated with the use of a [68Ga]PSMA in clinical studies (≤1% of 
patients). The most common adverse reactions were injection site pain and injection site 
erythema.  
 
Other general risks for PET/MRI imaging include: 


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 
The injection site may become infected. 
 
The dose might be extravasated into tissues surrounding the vein catheter leading to localized 
pain/discomfort. 
 
Radiation risks: [68Ga]PSMA injection contributes to lifetime radiation accumulation.  The 
smallest dosage for imaging and safe handling are used for these protocols. The organ and total 
body doses associated with [68Ga]PSMA imaging are comparable to those associated with other 
widely used clinical nuclear medicine procedures. 
 
6.8.2.3 Review of Safety Information 
As required by 21 CFR 312.32(b), the physician investigators will promptly review all information 
relevant to the safety of the drug. The physician investigators will also be providing much of this 
information to the local IRB as well for data safety and review monitoring.  The review will 
include determining whether there is a safety event over time and the causality.  Reporting will 
be as described in Table 4. 
 
Characterization of the severity of an Adverse Event:  Adverse events will be graded as below. 
 
Grade:  Grade denotes the severity of the AE.  An AE is graded using the following categories: 
 
Mild 
 
Moderate 
 
Severe 
 
Life-threatening or disabling 
 
Fatal 
 
NOTE:  Severity is graded on the Cancer Therapy Evaluation Program (CTEP) Common 
Terminology Criteria for Adverse Events (CTCAE) based scale for each adverse event. For 
example, an abnormal hemoglobin value is graded for severity from 1 to 5 [death] based upon 
where that value falls on the CTCAE scale of abnormal hemoglobin values.  “Severity” is NOT the 
same as “Seriousness.” All appropriate clinical areas should have access to a copy of the most 
current CTCAE and a copy of the CTCAE can be downloaded from (http://ctep.cancer.gov). 
 
Attribution of cause: The physician investigators will determine whether an adverse event was 
related to a medical treatment or procedure.  Definitions taken from our work with CTEP and 
NIH give the following definitions for “Attribution” that we will adopt for this IND study:  
Attribution is a clinical determination, by the investigator, as to whether an AE is related to a 
medical treatment or procedure.  Attribution categories are: 
 
Definite:     The AE is clearly related to a treatment or procedure 
 
 
Probable:   The AE is likely related to a treatment or procedure 
 
Possible:    The AE may be related to a treatment or procedure 
 
Unlikely:     The AE is likely unrelated to a treatment or procedure 
 
Unrelated:  The AE is clearly not related to a treatment or procedure 
 
NOTE:  Attribution is part of the assessment of an adverse event.  Determining that an event is 
‘unlikely related’ or ‘unrelated’ to a study agent or procedure does NOT make the event 
unreportable, or disqualify the event as an AE.  As defined above, an AE is reportable as 
specified herein if it occurred: “during the Adverse Event reporting period defined in the 
protocol, or by applicable guidance, regulation, or policy.” 


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6.8.2.4 Adverse Event Reporting 
Expedited AE reporting for this study will be done through the Cancer Consortium, IRB and FDA 
and as required by FDA MedWatch. These requirements are briefly outlined in the table below.  
 
Table 4.  Reporting Requirements. 
 
Unexpected 
Expected 
 
Adverse Reaction (known or suspected 
attributable to the use of [68Ga]PSMA 
AE not 
attributable to 
[68Ga]PSMA 
AE, AR 
 
Serious including life-
threatening (or death) 
Nonserious 
Life-Threatening 
or serious or not 
serious 
None are 
expected for 
[68Ga]PSMA 
Reporting 
Time 
Requirement 
to the FDA 
Report to FDA ASAP and 
within 7 days of discovery 
of event  
Annual 
Continuation 
Review 
submission 
Annual 
Continuation 
Review 
submission 
Not applicable to 
[68Ga]PSMA 
Reporting 
Form for the 
FDA 
IND Safety report of 
potentially serious risk  
Annual Reports / 
Case reports  
Annual Reports / 
Case reports 
Not applicable to 
[68Ga]PSMA 
Reporting 
Time 
Requirement 
to the local 
IRB 
Report to IRB ASAP within 
10 days of discovery of 
event (suspected is 
defined as 50% probability 
attributable to [68Ga]PSMA 
study) this also includes 
any increased risks with 
the study even without an 
AE 
At continuation 
review  time 
At continuation 
review time 
Not applicable to 
[68Ga]PSMA 
Reporting 
form for the 
IRB 
Expedited Reporting Form 
for Unanticipated 
Problems or 
Noncompliance and 
Adverse Event Reporting 
Form 
Form for 
Unanticipated 
Problems or 
Noncompliance, 
Case reports on 
continuation 
form, Data Safety 
Monitoring 
Reports 
Form for 
Unanticipated 
Problems or 
Noncompliance, 
Case reports on 
continuation 
form, Data Safety 
Monitoring 
Reports 
Not applicable to 
[68Ga]PSMA 
6.8.2.5 Expedited Adverse Reaction Reporting Guidelines 
Life-threatening (or fatal) adverse reactions must be reported within 7 days to the FDA.  The 
FDA should be notified as soon as the adverse reaction is discovered by telephone or fax or 
email.  The instructions and forms are available at 
http://www.fda.gov/Safety/MedWatch/HowToReport/default.htm  The report should be sent 


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ASAP by mail and followed with a follow-up report. Individual IND safety reports to FDA are 
submitted on the Medwatch FDA Form 3500A as an “IND Safety Report”.  The form should be 
sent to The Director, Office of Generic Drugs in the Center for Drug Evaluation and Research at 
FDA.  The address and phone numbers are available at:  
http://www.fda.gov/AboutFDA/CentersOffices/CDER/ucm119100.htm. 
 
All life threatening adverse reactions reports are submitted to the FDA, THE UAB IRB and to all 
investigators.  A copy of the report is kept on file. 
 
6.8.3 
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. 
 
6.9 Data Management 
All patient data will be anonymized and stored on encrypted password-protected computers with access 
only given to members of the research team. Standard precautions regarding HIPAA will be taken to 
avoid any breach in patient privacy. 
 
6.10 References 
 
1. 
Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP. Prostate specific membrane antigen 
expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. 
Cancer. 1998;82(11):2256-2261. 
2. 
Sweat SD, Pacelli A, Murphy GP, Bostwick DG. Prostate-specific membrane antigen expression is 
greatest in prostate adenocarcinoma and lymph node metastases. Urology. 1998;52(4):637-640. 
3. 
Wright GL, Jr., Haley C, Beckett ML, Schellhammer PF. Expression of prostate-specific membrane 
antigen in normal, benign, and malignant prostate tissues. Urol Oncol. 1995;1(1):18-28. 
4. 
Marchal C, Redondo M, Padilla M, et al. Expression of prostate specific membrane antigen 
(PSMA) in prostatic adenocarcinoma and prostatic intraepithelial neoplasia. Histol Histopathol. 
2004;19(3):715-718. 
5. 
Fendler WP, Eiber M, Beheshti M, et al. (68)Ga-PSMA PET/CT: Joint EANM and SNMMI 
procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 
2017;44(6):1014-1024. 
6. 
Algan O, Hanks GE, Shaer AH. Localization of the prostatic apex for radiation treatment planning. 
International journal of radiation oncology, biology, physics. 1995;33(4):925-930. 
7. 
Harris VA, Staffurth J, Naismith O, et al. Consensus Guidelines and Contouring Atlas for Pelvic 
Node Delineation in Prostate and Pelvic Node Intensity Modulated Radiation Therapy. 
International journal of radiation oncology, biology, physics. 2015;92(4):874-883. 
8. 
Schreibmann E, Schuster DM, Rossi PJ, Shelton J, Cooper S, Jani AB. Image Guided Planning for 
Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine) Positron Emission 
Tomography: Workflow and Initial Findings From a Randomized Trial. International journal of 
radiation oncology, biology, physics. 2016;96(1):206-213. 


Page 21 of 21 
Version 04/15/2021 
 
9. 
Girinsky T, Specht L, Ghalibafian M, et al. The conundrum of Hodgkin lymphoma nodes: to be or 
not to be included in the involved node radiation fields. The EORTC-GELA lymphoma group 
guidelines. Radiother Oncol. 2008;88(2):202-210. 
10. 
McDonald AM, Bishop JM, Jacob R, et al. Hypofractionated Prostate Radiotherapy with or 
without Conventionally Fractionated Nodal Irradiation: Clinical Toxicity Observations and 
Retrospective Daily Dosimetry. Prostate cancer. 2012;2012:546794. 
11. 
McDonald AM, Jacob R, Dobelbower MC, Kim RY, Fiveash JB. Efficacy and toxicity of 
conventionally fractionated pelvic radiation with a hypofractionated simultaneous versus 
conventionally fractionated sequential boost for patients with high-risk prostate cancer. Acta 
oncologica (Stockholm, Sweden). 2013;52(6):1181-1188. 
12. 
McDonald AM, Baker CB, Popple RA, et al. Different rectal toxicity tolerance with and without 
simultaneous conventionally-fractionated pelvic lymph node treatment in patients receiving 
hypofractionated prostate radiotherapy. Radiation oncology (London, England). 2014;9:129. 
13. 
Baker CB, McDonald AM, Yang ES, et al. Pelvic Radiotherapy versus Radical Prostatectomy with 
Limited Lymph Node Sampling for High-Grade Prostate Adenocarcinoma. Prostate cancer. 
2016;2016:2674954. 
14. 
Mohler JL, Armstrong AJ, Bahnson RR, et al. Prostate Cancer, Version 1.2016. J Natl Compr Canc 
Netw. 2016;14(1):19-30. 
15. 
Wei JT, Dunn RL, Litwin MS, Sandler HM, Sanda MG. Development and validation of the 
expanded prostate cancer index composite (EPIC) for comprehensive assessment of health-
related quality of life in men with prostate cancer. Urology. 2000;56(6):899-905.