Clinical trial NCT04264208
Conditions: Prostate Cancer
Sponsor: Andrei Iagaru
Start date: 2020-02-05; Completion date: 2022-12-14
Enrollment: 4 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
This study is being conducted to determine whether the combination of imaging agents 68-Ga RM2 and 68-Ga PMSA11 is better at assessing response to high dose rate (HDR) local therapy than standard imaging or biopsy in patients with known prostate cancer (PC)

Detailed description:
Primary Objective:

1. To demonstrate that 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI can detect additional cancers over mpMRI.
2. To demonstrate that 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI can assess changes in response to treatment and predict progression free survival (PFS) at 24 months.

Arms: arm 1: Subjects will undergo either 68Ga RM2 PET/MRI followed within 2 weeks by 68Ga PMSA11 PET/MRI. Two x intravenous (IV) 68Ga-RM2 PET/MRI with a 68Ga dosage of 140 mBq (3.8 mCi), +/- 20%, Two x intravenous (IV) 68Ga-PMSA11 PET/MRI with a 68Ga dosage of 111 to 259 mBq (3 to 7 mCi) arm 2: Subjects will undergo 68Ga PMSA11 PET/MRI followed within 2 weeks by 68Ga RM2 PET/MRI. Two x intravenous (IV) 68Ga-RM2 PET/MRI with a 68Ga dosage of 140 mBq (3.8 mCi), +/- 20%, Two x intravenous (IV) 68Ga-PMSA11 PET/MRI with a 68Ga dosage of 111 to 259 mBq (3 to 7 mCi)
Interventions: intervention 1: 68-Ga RM2. intervention 2: 68-Ga PSMA11 intervention 3: PET/MRI
Intervention descriptions: intervention 1: PET radiopharmaceutical intervention 2: PET radiopharmaceutical intervention 3: PET/MR scanner by GE healthcare

Protocol documents:
Prot_SAP_001.pdf: 
 
 
 
 
Evaluation of Patients With Low-Risk and Intermediate-Risk Prostate 
Cancer Scheduled for High-Dose Rate Brachytherapy Using 68-Ga-RM2 
PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
Study Protocol and Statistical Analysis Plan 
NCT04264208 
July 12, 2019 


IRB-51987 
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CONFIDENTIAL 
Protocol version 12 July 2019 
Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate 
Cancer Scheduled for High-Dose Rate Brachytherapy Using 68Ga-RM2 
PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
Principal Investigator / Protocol Director  
Andrei Iagaru, MD 
 
Stanford, CA 94305 
Phone:  650-725-4711 
Fax:  
 
Email:  aiagaru@stanford.edu 
 
Co-investigators 
Mark Buyyounouski, MD 
  
Stanford, CA  94305  
Phone:  
;  Fax:  
 
Email:  mbuyyou@stanford.edu 
Steven Hancock, MD 
 
Stanford, CA  94305  
Phone:  
;  Fax:  
 
Email:  shancock@stanford.edu 
Andreas Loening, MD, PhD 
 
Stanford, CA  94305  
Phone:  
;  Fax:  
 
Email:  loening@stanford.edu 
Guido Davidzon, MD 
 
Stanford, CA  94305  
Phone:  
;  Fax:  
 
Email:   gdavidzon@stanford.edu 
Shreyas Vasanawala, MD, PhD 
 
Stanford, CA  94304  
Phone:  
;  Fax:  
 
Email:  vasanawala@stanford.edu 
Christian Kunder, MD  
 
Stanford, CA  94305  
Phone:  
;  Fax:  
 
Email:  loening@stanford.edu 
Hilary Bagshaw, MD 
 
Stanford, CA  94305  
Phone:  
;  Fax:  
 
Email:  hbagshaw@stanford.edu 
Tanya Stoyanova, PhD 
 
Stanford, CA  94305  
Phone:  
 
Email:  stoyanova@stanford.edu 
Biostatistician 
, PhD 
  
Stanford, CA 94305-
 
  
Study Coordinator  
TBD 
Protocol IRB-51987  //  SRC-TBD  //  NCT-TBD 
Protocol version //  12 July 2019 
SRC Approval Date –  
 


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Protocol version 12 July 2019 
TABLE OF CONTENTS 
PROTOCOL SYNOPSIS 
4 
SCHEMA 
5 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
6 
1. 
OBJECTIVE 
7 
Specific Aim 
7 
2. 
BACKGROUND 
7 
2.1 Preliminary information 
7 
2.2 Study Agent 
10 
2.3 Clinicaltrials.gov 
11 
2.4 Rationale 
11 
2.5 Study Design 
14 
3. 
PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES 
17 
3.1 Inclusion Criteria 
17 
3.2 Exclusion Criteria 
17 
3.3 Informed Consent Process 
17 
3.4 Study Timeline 
17 
4. 
IMAGING AGENT INFORMATION 
17 
4.1 Study Agents 68Ga-PSMA-11 and 68Ga-RM2 
17 
4.2 Source of the Study Agent 
18 
4.3 Ordering 
18 
4.4 Agent Accountability 
18 
5. 
IMAGING SPECIFICS 
18 
5.1 Modality or Modalities to be used 
18 
5.2 Details of Imaging (ie, dynamic, static, number of scans, etc) 
18 
5.3 Image interpretation 
19 
6. 
STUDY PROCEDURES 
19 
6.1 Pre-Study 
19 
6.2 Imaging Days 
19 
6.3 Follow-up 
20 
6.4 Criteria for Removal from Study 
20 
6.5 Alternatives 
20 
7. 
STUDY CALENDAR 
20 


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8. 
ADVERSE EVENTS AND REPORTING PROCEDURES 
21 
8.1 Potential Adverse Events 
21 
8.2 Adverse Event Reporting 
21 
9. 
REGULATORY CONSIDERATIONS 
21 
9.1 Institutional Review of Protocol 
21 
9.2 Data Management Plan 
21 
10. Statistical Considerations and Evaluation of Results 
22 
10.1 Study Endpoints 
22 
10.2 Accrual estimates 
24 
10.3 Study Outcomes (ClinicalTrials.gov) 
24 
10.4 Analyses Plans 
25 
10.5 Accrual estimates 
25 
11. REFERENCES: 
27 
3.1 Inclusion Criteria 
34 
3.2 Exclusion Criteria 
34 
 


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PROTOCOL SYNOPSIS 
TITLE 
Evaluation of Patients with Low-Risk and Intermediate-Risk 
Prostate Cancer Scheduled for High-Dose Rate Brachytherapy 
Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric 
MRI 
STUDY PHASE 
Phase 2 study 
INDICATION 
Prostate cancer 
INVESTIGATIONAL 
PRODUCTS  
68Ga-PSMA-11;  also known as: 
• 
DFKZ-11 
• 
HBED-CC PSMA 
• 
The “Heidelberg compound” 
68Ga-RM2;  also known as: 
• 
Bombesin 
• 
BAY86-7548 
SAMPLE SIZE  
100 participants 
PRIMARY OBJECTIVES 
To demonstrate that 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI can 
detect additional cancers over mpMRI 
To demonstrate that 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI can 
assess changes in response to treatment and predict PFS at 24 
months 


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Protocol version 12 July 2019 
 
SCHEMA 
 
 
Eligible participant with known prostate cancer 
Randomizaton to:  
Schedule A 
68Ga-PSMA11 PET/MRI 
Followed within 2 weeks by 
68Ga-RM2 PET/MRI 
OR 
Schedule B 
68Ga-RM2 PET/MRI 
Followed within 2 weeks by 
68Ga-PSMA11 PET/MRI 
HDR 
At least 3 days later: 
Schedule A 
68Ga-PSMA11 PET/MRI 
Followed within 2 weeks by 
68Ga-RM2 PET/MRI 
OR 
Schedule B 
68Ga-RM2 PET/MRI 
Followed within 2 weeks by 
68Ga-PSMA11 PET/MRI 


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Protocol version 12 July 2019 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
Ga-68; 68Ga 
Gallium-68 
IRB 
Institutional Review Board 
IV 
Intravenous 
MRI 
Magnetic resonance imaging 
NPV 
Negative predictive value  
PPV 
Positive predictive value  
PET 
Positron emission tomography 
SUV 
Standardized Uptake Value 
PSMA 
Prostate specific membrane antigen 
GRPR 
Gastrin releasing peptide receptor 
PRCA 
Prostate cancer 
HIFU 
High-intensity focused ultrasound 
HDR 
High-dose rate 
 


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Protocol version 12 July 2019 
1. OBJECTIVE 
Specific Aims 
Aim 1: 68Ga-RM2 PET/MRI and 68Ga PSMA-11 PET/MRI detection of PC. We will investigate the 
performance of the new GRPr-binding PET radiopharmaceutical, 68Ga-RM2, and compare it to the 
currently most widely investigated (but not FDA-approved) PC PET radiopharmaceutical, 68Ga 
PSMA-11, as well as to mpMRI acquired during PET/MRI for the localization and staging of low-risk 
and intermediate-risk PC. New lesions identified on PET/MRI and not known from prior systematic 
prostate biopsy will be confirmed by targeted biopsy and GRPr and PSMA status will be evaluated 
with specific immunohistochemical stains [1, 2]. 
Aim 2: 68Ga-RM2 PET/MRI and 68Ga PSMA-11 PET/MRI prediction of PFS after local targeted 
therapy for PC. We will investigate if the combination of the GRPr-binding PET imaging agent, 68Ga-
RM2, and the most widely investigated (but not FDA-approved) PSMA-binding PET imaging agent, 
68Ga PSMA-11, together with mpMRI can predict PFS after local targeted therapy. We will 
determine if 68Ga-RM2 PET/MRI and 68Ga-PSMA-11 PET/MRI assessment at 6-months follow-up 
will predict PFS at 24 months based on standard clinical follow-up (PSA, imaging, tissue diagnosis). 
 
2. BACKGROUND 
2.1 Preliminary information 
Prostate cancer (PC) remains the most-common non-cutaneous cancer diagnosed in American 
males, accounting for an estimated 164,690 estimated new cases and 29,430 estimated deaths in 
2018 [3]. Historically, PC often presented as painful metastatic disease, and killed up to 40 per 
100,000 men annually in the US between 1991 and 1993. The introduction of widespread PSA 
screening in the early 1990’s led to a profound stage migration with most cancers detected while 
localized to the prostate. Subsequently PC-specific mortality dropped to 20 per 100,000 by 2012 [4]. 
While improvements in therapy likely play some role, independent groups in the CISNet consortium 
have shown through modeling that 45% - 70% of the decline in PC mortality can be plausibly 
attributed to PSA screening [5].  
Meanwhile, PSA screening also dramatically increased detection and treatment of slow-growing, 
low-grade PC that would have otherwise remained asymptomatic. Treating all these cancers with 
radical prostatectomy or external beam radiotherapy (EBRT) is expensive to the healthcare system 
and led to significant short and long-term side effects in hundreds of thousands of men. As a result, 
despite the ~50% reduction in age-specific PC mortality in the PSA era, the US Preventive Services 
Task Force (USPTF) recommended in 2011 against routine screening with PSA [6] because it 
deemed that the harms of screening outweighed the benefits. Accordingly, PSA use and early 
diagnosis PC have decreased dramatically [7]. The dilemma for patients and treating physicians is: 
either continue screening despite the problem of overtreatment and treatment-related side effects, 
or do not screen and miss the opportunity for early diagnosis and cure. To reduce the harms of 
screening while maintaining the benefits, there is a clear need for faster, less invasive and 
fundamentally less risky treatments for localized PC. 
Standard treatment options include observation, surgery (prostatectomy), radiation therapy 
(external beam or brachytherapy), and/or hormonal therapy, depending on the initial stage, the 
patient’s age, co-morbidities, and preferences. If T-stage is greater than 2 or if the PSA > 20 ng/mL 
or if Gleason score is > 8, there is an increased risk of metastatic disease and cross-sectional 
imaging and bone scans are performed to identify metastases. However many cancers are 
diagnosed before this stage and are candidates for targeted local therapy. 
Changing paradigms in management of localized PC. Not all localized PC have the same biologic 


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potential; most men with small, non-aggressive (Gleason 3+3) cancers can be safely followed by 
‘active surveillance’ – a strategy that has gained acceptance in the last 5 years [8]. Low-risk PC 
(Gleason score ≤6, pretreatment PSA level <10 ng/mL, and clinical stage T1–T2a) is a group that 
accounts for 35% to 70% of all patients with PC [9, 10]. But for the remaining patients with higher 
grade, clinically significant cancers still merit treatment. They face a difficult choice: aggressive 
whole-gland treatment that risks life-altering side effects, vs. no treatment and the risk of cancer 
progression, metastasis and potential death [11]. Newer less invasive local therapies seek to offer 
treatment options that are faster, less invasive, less risky and potentially cheaper than surgery or 
EBRT. These include ablation with heating (high-intensity focused ultrasound - HIFU, microwaves, 
or lasers), freezing (with needle cryoprobes), electroporation, stereotactic radiation therapy and 
brachytherapy. Such localized therapies are becoming popular despite limited long-term evidence 
of tumor control, especially for ablation modalities.  
The role of multi-parametric MRI (mpMRI) for guiding care. While PC is most often multifocal, the 
highest grade, index lesion drives clinical outcomes [12, 13]. Conventional trans-rectal ultrasound 
(TRUS)-guided systematic prostate biopsy consisting of 6-12 biopsy cores is limited by under-
diagnosis of index lesions and over-diagnosis of small, non-aggressive tumors that pose little threat 
to a man’s life. Use of mpMRI is increasing rapidly due to its ability to improve detection of clinically 
significant index tumors using MRI-guided biopsy [14]. MRI-guided biopsies find more clinically 
significant tumors (≥G7) and less insignificant (G6) tumor than conventional systematic biopsies. 
MRI is increasingly used for the following: 
• 
Prior to biopsy, MRI can be used to determine if biopsy is necessary and can enable image-
targeted biopsy if an abnormality is seen on MRI [14]  
• 
Men contemplating active surveillance: a normal mpMRI adds confidence that this is a safe 
management option. An abnormal mpMRI prompts a conventional MRI-transrectal ultrasound 
(MRI-TRUS) fusion biopsy that often reveals clinically significant cancer that warrants treatment 
[15].  
• 
Men deciding between whole-gland treatment (surgery or radiation) and partial-gland focal 
ablation. Finding a single tumor on MRI prompts consideration of focal ablation. Finding multiple 
and/or bilateral tumors prompts consideration of whole-gland treatment (surgery or radiation). 
Finding extracapsular disease (T3 / T4) prompts workup for potential metastatic cancer. 
It should be noted that mpMRI has limitations: ~20% of all index lesions are missed [16], the size of 
high-grade cancers is underestimated [17], and ~40% of men with a normal MRI have PC on 
biopsy [18]. 
Positron emission tomography (PET) and PC. PET tracers, such as 18F- or 11C-labeled choline and 
[11C]-acetate, are used mainly for the diagnosis of recurrent [19-21] or metastatic [22] PC. Their 
feasibility in primary diagnosis is limited because of uptake in benign tissue such as benign 
prostatic hyperplasia or inflammatory lymph nodes [23, 24]. Although choline based PET/CT is 
widely used outside the US for imaging PC, there have been numerous studies reporting a low 
sensitivity and specificity, especially at low PSA levels [25, 26]. Consequently, improved molecular 
imaging of PC is necessary. One novel method is PET imaging with 18F-FACBC, a synthetic amino 
acid. Nanni et al. indicate that this tracer might be superior when compared to choline PET/CT [27]. 
However, others shown that 18F-FACBC uptake in PC is similar to that in BPH nodules [28]. 
Prostate-specific membrane antigen (PSMA) is a transmembrane protein of high interest in PC. 
This cell surface protein is significantly overexpressed in PC cells when compared to other PSMA-
expressing tissues such as kidney, proximal small intestine or salivary glands. PSMA is highly 
overexpressed on almost all PC [29-31]. Only 5-10% of primary PC lesions have been shown to be 
PSMA-negative [32, 33], making this class of radiopharmaceuticals suitable for diagnosis of primary 
PC and for initial staging [34-39]. Non-invasive tumor grading has also been reported [40]. PSMA 
ligands can be labeled with 68Ga for PET imaging [41]. Experience with PET/CT using Glu-NH-CO-
NH-Lys-(Ahx)-[68Ga(HBED-CC)] (68Ga-PSMA-11) indicates that this compound can detect PC 
relapses and metastases with high contrast by binding to the extracellular domain of PSMA, 


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followed by internalization [42]. Better localization of cancer within the prostate itself would also 
have a clinical impact by guiding image-targeted biopsy and patient selection for local targeted 
therapy. However, these promising agents do not detect all recurrences [43, 44] and other cancers 
also express PSMA [45-47]. False positive findings have also been reported using PSMA agents 
[48-51].  
Consequently, improved imaging of PC continues to be an area of unmet clinical need. Gastrin-
releasing peptide (GRP) is a 27-amino acid neuropeptide that is the mammalian homologue of the 
linear tetradecapeptide bombesin. It shares homology with bombesin at the C-terminal amidation 
sequence in the final 7 amino acids [52, 53]. The GRP receptor (GRPr) is the only well 
characterized receptor to which GRP and bombesin bind with a high affinity. GRPr belongs to a 
family of G-coupled protein receptors, and the GRP binds selectively to the GRPr [52, 53]. Studies 
show that GRPr is expressed at very low levels in normal prostate glands but is increased in 45-
100% of human PCa [54, 55]. 68Ga-labeled DOTA-4-amino-1-carboxymethyl-piperidine-D-Phe-Gln-
Trp-Ala-Val-Gly-His-Sta-Leu-NH2 (68Ga-RM2, formerly also known as BAY86-7548 or 68Ga-DOTA-
Bombesin) is a synthetic bombesin receptor antagonist, which targets GRPr [56]. GRPr proteins are 
highly overexpressed in several human tumors, including PC [57]. Because of their low expression 
in BPH and inflammatory prostatic tissues [58, 59], imaging of GRPr has potential advantages over 
current choline- and acetate-based radiotracers. Indeed, preclinical studies using BAY86-7548 have 
shown a high and persistent tracer uptake in mice bearing PC-3 tumor xenografts, which represent 
androgen-independent human PC with high GRPr expression [60]. Clinically translated GRPr 
antagonists PET radiopharmaceuticals include 68Ga-RM2, 68Ga-SB3, 68Ga-NeoBOMB1, 18F-BAY-
864367 and 64Cu-CB-TE2A-AR06. They have been shown to have stable biodistribution in healthy 
volunteers [61] and mean effective doses comparable to other radiopharmaceuticals [62, 63]. 
Published data indicate encouraging results for use at initial diagnosis of PC [61-65] or at 
biochemical recurrence [66]. 
While the PSMA is over-expressed in prostate cancer, this is not universal; there are lesions 
undetected by PSMA-targeted imaging in different risk classes or stages of disease. The influence 
of GRPr expression on cancer grade and stage has been evaluated by several groups. Nagasaki 
et al. found that GRPr expression is correlated with higher Gleason score [67]. Most recently, 
Michaud et al. showed that GRPr expression in PC is independent from PSMA expression. In 
some cases GRPr expression occurred in the absence of detectable PSMA expression on IHC [2]. 
Evolution of Radiotherapy. Localized PC is effectively treated with external beam radiation therapy 
(EBRT) to 78 to 80 Gy, a non-invasive, outpatient treatment regimen. It requires approximately 40 
fractions, or treatments, delivered 5 days/week over 2 months, necessitating a significant time 
commitment from patients. Potential side effects include urinary urgency, dysuria, hematuria, 
urinary retention, impotence, and GI toxicity. Biochemical failure (rising PSA after treatment) may 
occur in as many as 20-30% of men after EBRT for intermediate risk PC [68]. Low dose rate (LDR) 
brachytherapy with trans-perineal radioactive seed implantation can deliver potentially higher local 
doses which is important for local tumor control. However, seed placement is challenging with real-
time planning and seed placement resulting in variable dosimetry, and the radioactive seeds 
mandate contact restrictions for patients. Recently, high dose rate (HDR) brachytherapy has been 
utilized as an alternative. Although usually done under general anesthesia, HDR is minimally 
invasive, enables real time treatment planning, the ability to preferentially boost dominant tumor 
locations, and has favorable dosimetry [69]. Local control after HDR is excellent [70], the treatment 
is more convenient for patients and side effects are less common than after EBRT as the radiation 
is delivered with a sharp fall-off minimizing dose to surrounding pelvic structures. At Stanford, we 
have an active, well-established HDR brachytherapy program led by Dr. Mark Buyyounouski who 
consistently treats at least 6 patients per week with this technique. Since initiation of the program 
approximately 3 years ago, we have treated over 500 patients with this modality either as part of a 
boost treatment in addition to EBRT (325 patients) or as HDR monotherapy (175 patients) for 
definitive treatment of their PC. These include 45 patients to date in 2018 with low or intermediate 


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Protocol version 12 July 2019 
risk PC. 
Efficacy assessment: a major unsolved question. Unlike after prostatectomy, where PSA levels 
fall to zero soon after successful surgery, after local targeted therapy (HDR) PSA levels are poor 
measures of efficacy. PSA falls to a variable nadir due to continued production by residual prostate 
tissue as well as potential occult non-index tumor that was outside the boost region. Even the 
Phoenix criterion for radiation failures (2 ng/ml rise above nadir), now a de facto standard, has a 
sensitivity and specificity of only ~65% and ~77%, respectively, for clinical recurrence [71]. False 
negatives may occur early because it takes time for tumor to grow back fast enough to generate 2 
ng/ml of PSA. False positives may be due to residual BPH, regeneration of normal prostate tissue, 
and prostatitis. PSA is especially problematic for ablation because some portions of the gland are 
left entirely untreated. The potential for residual under-treated target tumor, or occult non-target 
tumor to progress, and potentially become clinically significant, highlights the unmet need for 
sensitive surveillance methods after local targeted therapy.  
Therapeutic options after local treatment. Evidence from salvage treatment for post-prostatectomy 
recurrence reveals that success is more likely when treatment is initiated early [72]. One theoretical 
advantage of local treatments is that tissue damage is restricted to the prostate. This enables 
options for local retreatment and second line therapy after failure. After brachytherapy, local 
recurrence can potentially be retreated with more brachytherapy. This ability to retreat further 
highlights the need for sensitive surveillance methods after initial treatment. 
Can mpMRI also help find recurrence or residual tumor after local targeted therapy? It is much 
more difficult to interpret mrMRI after treatment [73]. For example, after radiation therapy, 
decreased exocrine function, and fibrosis can cause low signal on T2-weighted images and variable 
diffusion restriction that mimic tumor [74]. Similarly, after ablation, resolving hemorrhage and 
proteinaceous necrosis can cause variable diffusion restriction, and inflammation can cause 
contrast enhancement [75]. 
Simultaneous PET/MRI: PET/MRI is an advanced hybrid imaging technology that can provide both 
biological and morphological information of various biological pathways, as discussed in more 
details in “Approach”. Compared to PET/CT, simultaneous PET/MRI has advantages resulting from 
reduced radiation exposure and higher soft tissue contrast [76]. PET/MRI is particularly important 
for accurate localization and assessment of the pelvic extent of disease at the initial staging of PC. 
In fact, the majority of pathologic findings leading to up-staging are microscopic, requiring the high 
resolution of intraprostatic anatomy and adjacent structures afforded by co-registration with MRI 
rather than CT [77]. In addition, the silicon photomultipliers (SiPM) based PET detectors in SIGNA 
PET/MRI or digital PET/CT scanners are more sensitive than photomultiplier tubes (PMT) based 
PET detectors in standard PET/CT [78-80]. The knowledge we propose to acquire can be 
generalized to separately acquired PET/CT and mpMRI, although motion artefacts and other factors 
may prevent accurate fusion of the data. 
In summary, some men could undergo ineffective local treatment and miss the chance for effective 
local salvage treatment before metastasis occurs. 
2.2 Study Agent 
This study will use 68Ga-RM2.  This PET radiopharmaceutical has previously been identified as 
68Ga-DOTA Bombesin or BAY86-7548.  This is not an FDA-approved product.  This protocol is 
submitted to IND
, the IND to which this protocol is submitted. 


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This study will also use 68Ga-PSMA11.  This PET radiopharmaceutical has previously been 
identified as DFKZ-11;  HBED-CC PSMA;  or the “Heidelberg compound.”  This is not an 
FDA-approved product, and is described in detail in IND 128379. 
2.3 Clinicaltrials.gov  
This study will be registered on ClinicalTrials.gov. 
2.4 Rationale 
In this study, we propose to use a well-established PET isotope, Gallium-68 (68Ga), bound to a 
PSMA ligand  ie, 68Ga-PSMA-11) and a GRPR ligand (ie, 68Ga-RM2) that have high affinity for 
prostate specific membrane antigen and gastrin releasing peptide receptors, respectively.  
Therefore, we propose the following goals: 
1. To demonstrate that 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI can detect additional cancers over 
mpMRI. 
2. To demonstrate that 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI can assess changes in response to 
treatment and predict PFS at 24 months. 
68Ga-RM2 at Stanford University: Under an FDA-approved IND (# 
) our group currently 
uses 68Ga-RM2 in 2 clinical scenarios, either prior to prostatectomy in patients with intermediate or 
high-risk PC or at biochemical recurrence after definitive treatment (prostatectomy or radiation 
therapy). 
68Ga-RM2 identified primary PC lesions in all 15 
patients scheduled for prostatectomy included in 
our pilot study [81]. An example is shown in 
Figure 1. 
We recently published our results using 68Ga-
RM2 PET/MRI in 32 patients with biochemical 
recurrence of PC and negative conventional 
imaging (bone scintigraphy and CT or MRI) [66]. 
Currently, we have 80 participants scanned at 
BCR and our data indicates a 70% detection rate 
in this population with a mean PSA of 8.0 ng/dl 
and negative conventional imaging. The lowest 
PSA in a patient with positive 68Ga-RM2 PET was 
0.24. One third of the lesions found on 68Ga-
RM2 PET were biopsied; all results were true 
positive. Examples are shown in Figure 2. More 
importantly in our opinion, PSA velocity values 
were 0.32±0.59 ng/ml/year (range: 0.04-1.9) in 
patients 
with 
negative 
PET 
scans 
and 
2.51±2.16 ng/ml/year (range: 0.13-8.68) in patients with positive PET scans (P=0.006), 
suggesting the ability to detect more aggressive PC.  
 
 
 


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68Ga PSMA-11 at Stanford University: 68Ga PSMA-11 is under clinical investigation in the US, 
although it is widely used elsewhere despite lack of regulatory approval. We are currently 
conducting prospective studies under IND #128379 in the same indications as for 68Ga-RM2 (prior 
to prostatectomy in patients with intermediate or high-risk PC or at biochemical recurrence after 
definitive treatment).  
To date we enrolled 49 men with intermediate and high risk newly diagnosed PC, scheduled to 
undergo prostatectomy and pelvic nodal dissection [82]. 68Ga PSMA-11 PET identified intraprostatic 
cancer in all 49 patients, while mpMRI alone identified PIRADS 4 or 5 lesions in ¾ of patients. 68Ga 
PSMA-11 PET showed focal uptake in pelvic lymph nodes in 9 patients. Final pathology confirmed 
cancer in the prostate of all patients. No 
patient 
with 
normal 
pelvic 
nodes 
on 
PET/MRI had metastases on pathology. An 
example is shown in Figure 3. 
 
In addition, we now have data from 62 
patients with BCR PC who had 68Ga PSMA-
11 PET/CT at our institution [83]. 
68Ga 
PSMA-11 detected sites of recurrence in 73% of patients, with the lowest PSA and a positive scan 


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Protocol version 12 July 2019 
at 0.05 ng/mL. Examples are shown in Figure 4. 
 
68Ga-RM2 vs. 68Ga PSMA-11 at Stanford University: We first published a pilot comparison of 
68Ga-PSMA-11 with 68Ga-RM2 at BCR [84]. There were 45 areas of high 68Ga-PSMA uptake that 
corresponded 
to 
metastases 
shown on the CT 
images 
in 
the 
bone 
marrow 
(n=13), 
retroperitoneal 
lymph 
nodes 
(n=12), 
mediastinal lymph 
nodes 
(n=8), 
pelvic 
lymph 
nodes 
(n=9), 
seminal 
vesicle 
(n=2), 
and 
subclavian lymph 
node (n=1). 68Ga-
RM2 uptake was high in all these areas, except for one pelvic lymph node and seminal vesicle in 
the same patient. 68Ga PSMA-11 uptake and/or clearance in the bowel made assessment of small 
retroperitoneal lymph nodes more difficult compared to 68Ga-RM2 in 2 participants. 68Ga-RM2 
shows similar sensitivity to 68Ga-PSMA and provides higher lesion conspicuity in selected patients 
due to no significant hepatobiliary clearance (Figure 5).  
At this time, we enrolled 9 patients with intermediate and high risk newly diagnosed PC, scheduled 
to undergo prostatectomy and pelvic nodal dissection, in a prospective comparison of 68Ga-RM2 
and 68Ga-PSMA-11. At least one lesion in the prostate was identified by each radiopharmaceutical 
in every participant, but the results did not overlap, as shown in Figure 6. 
Another study at our institution enrolled 29 
patients with BCR PC in a direct comparison of 
68Ga-RM2 and 
68Ga-PSMA-11. 
68Ga-PSMA 
found sites of disease in 22/29 patients and 
68Ga-RM2 
identified 
recurrent 
prostate 
cancer in 20/29 patients. 68Ga-PSMA-11 was 
positive and 68Ga-RM2 was negative in 3 
patients; 68Ga-PSMA-11 was negative and 
68Ga-RM2 was positive in 2 patients. More 
lesions were seen on 68Ga-PSMA-11 than 
on 68Ga-RM2 in 4 patients, while 68Ga-RM2 
identified more lesions than 68Ga-PSMA-11 
in 3 patients. PSA was 0.4-36.4 ng/mL; 
mean±SD: 8.3±8.8) in patients with positive 
68Ga-PSMA-11 and 0.3-36.4 ng/mL; mean±SD: 


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8.8±9.1) in patients with positive 68Ga- RM2 (P: 0.86). PSA was 0.2-8.2 ng/mL; mean±SD: 2.5±3.2) 
in patients with negative 68Ga-PSMA-11 and 0.2-8.2 ng/mL; mean±SD: 2.7±2.9) in patients with 
negative 68Ga- RM2 (P: 0.90). Examples are shown in Figure 7. 
PSMA is over-expressed in many but not all PC; some lesions will not be detected by PSMA-
targeted imaging 
in 
different 
risk 
classes or stages 
of disease. The 
influence of GRPr 
expression on PC 
grade and stage 
has 
been 
evaluated 
by 
several 
groups. 
Nagasaki 
et al. 
found that GRPr 
expression 
is 
correlated with higher Gleason score [67]. GRPr expression in PC is independent from PSMA 
expression and GRPr expression can occurr in the absence of detectable PSMA expression on 
IHC [2]. Therefore, GRPr PET is complementary to 
PSMA PET for detection of PC. The use of both 
PET 
radiopharmaceuticals 
will 
ensure 
appropriate evaluation of PC patients. 
Figure 8 shows a patient with local recurrence of PC 
identified with 68Ga-RM2 and subsequently treated 
with HDR brachytherapy, showing resolution of 68Ga-
RM2 uptake in the prostate bed. 
In summary, GRPr and PSMA expression is 
increased in PC, due to different underlying biological 
processes. By using a novel approach combining 
both 68Ga-RM2 and 68Ga-PMSA-11 PET/MRI within 
each patient, we will be able to accurately identify PC 
and we will attempt to predict PFS after targeted 
therapy. 
We hypothesize that the use of 68Ga-RM2 and 68Ga-
PSMA-11 PET/MRI will permit accurate localization 
of PC at initial diagnosis and allow for evaluation of 
response to treatment and prediction of PFS at 24 
months after local targeted therapy. We will use a 
state-of-the-art simultaneous PET/MRI scanner with time of flight capability that was first-ever 
installed system at Stanford University in December 2013. There are now more than 200 
simultaneous PET/MRI systems world-wide and we collaborate with many of these sites. 
2.5 Study Design 
This is a NCI-funded phase II study with a total of 100 participants with known prostate cancer, 
scheduled to undergo HDR local therapy.  All patients will first be seen by a Stanford Cancer 


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Institute physician and then referred if appropriate on clinical grounds to Dr Iagaru or his colleagues 
for this study.  Eligible participants will undergo baseline assessments at enrollment.  The following 
steps will take place after the participant has signed the written consent (participants will be 
randomized to have 68Ga-RM2 first followed by 68Ga-PSMA11 within 2 weeks or 68Ga-PSMA11 first 
followed by 68Ga-RM2 within 2 weeks [50/50 chance for each schedule]).  After the 1st scan, the 
2nd scan will only occur after the follow-up with the patient for the 1st scan, and after a minimum of 
3 days have elapsed.   
Scan 1 
1. Participants will be given a copy of the consent form s/he signed  
2. Participant will be asked to drink 1 to 2 glasses of water before arrival at the clinic 
3. Vital signs (heart rate, blood pressure) will be recorded 
4. Participant will be injected IV with 140 ± 20% mBq of 68Ga-RM2  OR  3 to 7 mCi of 
68Ga-PSMA11.  
5. Participant will void immediately prior to the scan 
6. Approximately 45 minutes after the radiopharmaceutical IV administration, data acquisition 
will begin in the pelvic region and move toward the head.  First, localizer MRI scans will be 
performed to define the table positions.  After correct positioning of the spatial acquisition 
windows is ensured, the combined PET/MRI acquisition will be initiated with 3 to 5 table 
positions at a 2 to 4-min acquisition time per table position. 
7. Participants will be dismissed. 
8. Vital signs (heart rate, blood pressure) will be recorded again at the completion of the study 
9. Participants will be contacted at 24 to 72 hours following the scan in order to capture 
potential occurring Adverse Events. 
Scan 2 
1. Participant will be asked to drink 1 to 2 glasses of water before arrival at the clinic 
2. Vital signs (heart rate, blood pressure) will be recorded 
3. Participant will be injected IV with 3 to 7 mCi of 68Ga-PSMA11  OR  140 ± 20% mBq of 
68Ga-RM2 (ie, the radiopharmaceutical not administered for Scan 1)   
4. Participant will void immediately prior to the scan 
5. Approximately 45 to 60 minutes after the radiopharmaceutical IV administration, data 
acquisition will begin in the pelvic region and move toward the head.  First, localizer MRI 
scans will be performed to define the table positions.  After correct positioning of the spatial 
acquisition windows is ensured, the combined PET/MRI acquisition will be initiated with 
3 to 5 table positions at a 2 to 4 minute acquisition time per table position.  Only MR 
sequences required for attenuation correction of PET data will be acquired. 
6. Vital signs (heart rate, blood pressure) will be recorded again at the completion of the study. 
7. Participants will be contacted at 24 to 72 hours following the scan in order to capture 
potential occurring Adverse Events. 


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The above will be repeated approximately 6 months after HIFU or HDR local treatment, prior to 
standard of care biopsy to evaluate for residual disease in the prostate. 
Objectives of the Study 
Primary Objectives 
• 
To demonstrate that 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI can detect additional 
cancers over mpMRI. 
• 
To demonstrate that 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI can assess changes in 
response to treatment and predict PFS at 24 months. 
Secondary Objective 
• 
None 
 
Endpoints 
Primary Endpoints 
• 
Number of participants with assessable additional prostate cancedr lesions over mpMRI 
• 
Number of participants with assessable pre- and post-treatment uptake in response to 
HIFU or HDR local therapy 
Secondary Endpoint 
• 
None 


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3. PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES 
3.1 Inclusion Criteria 
• 
Patients must be at least 18 years of age;  
• 
Patients must be able to provide informed consent;  
• 
Histologically proven low-grade or intermediate-grade PC;  
• 
Scheduled to undergo targeted local therapy (HDR brachytherapy). 
3.2 Exclusion Criteria 
• 
Inability to lie still for the entire imaging time;  
• 
Inability to complete the needed investigational and standard-of-care imaging 
examinations due to other reasons (severe claustrophobia, radiation phobia, etc.);  
• 
Any additional medical condition, serious intercurrent illness, or other extenuating 
circumstance that, in the opinion of the Investigator, may significantly interfere with study 
compliance;  
• 
Metallic implants (contraindicated for MRI). 
3.3 Informed Consent Process 
All participants will be provided a consent form describing the study with sufficient information for 
participants to make an informed decision regarding their participation.  Participants must sign the 
IRB-approved informed consent 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.   
3.4 Study Timeline 
3.4.1 Primary Completion: 
The study will reach primary completion 24 months from the time the the last subject completes the 
first scan. 
3.4.2  Study Completion: 
The study will reach study completion 84 months from the time the study opens to accrual. 
4. IMAGING AGENT INFORMATION 
4.1 Study Agents 68Ga-PSMA-11 and 68Ga-RM2  
68Ga-PSMA-11  
This study will use 68Ga-PSMA-11 as the PET radiopharmaceutical.  This agent has previously been 
identified as DFKZ-11;  HBED-CC PSMA;  or the “Heidelberg compound.”  
The administered dosage of 68Ga-PSMA-11 is 111 to 259 mBq (3 to 7 mCi) IV.  We will use 
68Ga-PSMA-11 as the PET radiopharmaceutical.  There are 2 publications on dosimetry for 
68Ga-PSMA-11 (PMID:  27260521; 28012435).  The first lists 0.0236 mSv/MBq for the mean effective 
dose, while the other indicates 0.0258 mSv/MBq.  We used the maximum potential administered 


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activity of 7 mCi and the higher of the reported dosimetry values.  Therefore, 
259 mBq x 0.0258 mSv/MBq = 6.68 mSv. 
To summarize the results of the published human studies, there were no observed adverse events to 
the radiopharmaceutical.  The measured dosimetry showed that the critical organ with 68Ga-PSMA-11 
is the spleen, followed by the stomach wall;  pancreas;  and bladder wall.  The effective dose of 
68Ga-PSMA-11 reported (0.0258 mSv/MBq) is similar to those of 68Ga-DOTA-TOC (0.023 mSv/MBq), 
68Ga-DOTA-NOC (0.025 mSv/MBq), 68Ga-DOTA-TATE (0.021 mSv/MBq) and 68Ga-NOTA-RGD 
(0.022 mSv/MBq) [85-88].   
68Ga-RM2  
This study will also use 68Ga-RM2 as the PET radiopharmaceutical.  The administered dosage is 
140 ± 20% mBq IV.  Measured human dosimetry data are available from published data [89].  
68Ga-RM2 is rapidly excreted through the kidneys to the urinary bladder and accumulated 
predominantly in the pancreas and liver.  Maximum peak uptake of the total injected radioactivity was 
seen in the urinary bladder contents and the liver, with approximately 36% and 14%, respectively. 
The organ with the highest absorbed dose was the urinary bladder wall at 0.61 mSv/MBq, followed by 
the pancreas at 0.51 mSv/MBq.  The mean effective dose (14) was 0.051 mSv/MBq.  Thus, the 
effective dose from a 140 MBq injected radioactivity is 7.7 mSv, which could be reduced to roughly 
4.76 mSv with frequent bladder voiding (1-h voids). 
To summarize the results of the published human dosimetry study, there were no observed adverse 
events to the radiopharmaceutical.  The measured dosimetry showed that the critical organ with 
68Ga-RM2 is the urinary bladder, followed by the pancreas.  The effective dose of 68Ga-RM2 reported 
(0.051 mSv/MBq) is approximately twice as much as those of 68Ga-DOTA-TOC (0.023 mSv/MBq), 
68Ga-DOTA-NOC (0.025 mSv/MBq), 68Ga-DOTA-TATE (0.021 mSv/MBq) and 68Ga-NOTA-RGD 
(0.022 mSv/MBq) [85-88]. 
4.2 Source of the Study Agent  
Molecular Imaging Program at Stanford (MIPS) 
Satellite Radiochemistry Facility  
300 Pasteur Dr, C21 
Stanford, CA 94305  
4.3 Ordering 
Ordered in Radiology Information System (RIS), address per above. 
4.4 Agent Accountability 
RIS is password-protected and part of the electronic medical records. 
5. IMAGING SPECIFICS  
5.1 Modality or Modalities to be used 
PET/MRI 
5.2 Details of Imaging (ie, dynamic, static, number of scans, etc) 
A localizer MRI scan will be performed at 45 minutes after injection of 140 ± 20% mBq of 68Ga-RM2 
(or 3 to 7 mCi of 68Ga-PSMA11, depending on randomization) to define the table positions.  After 


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correct positioning of the spatial acquisition windows is ensured, the combined PET/MRI acquisition 
will be initiated with 3 to 5 table positions at a 2 to 4 min acquisition time per table position.  A 
volumetric T1 acquisition with fat-water separation and motion correction to enable free-breathing 
will be obtained at each table position and used for the generation of attenuation maps and for 
anatomic allocation of the PET results.  Simultaneously with the start of the T1 MRI sequence, the 
PET acquisition will start at the same table position, thus ensuring optimal temporal and regional 
correspondence between MRI and PET data.  The PET acquisition time will be 4 min per table 
position, taking delayed acquisition times and radioactive decay into account.  As the T1 will take 
less than 4 minutes, a rapid diffusion weighted MRI will also be performed.  After completion of the 
PET acquisition, the table will be moved to the next table position and the procedure will be 
repeated.  Upon completion of the PET acquisition for all stations, volumetric post-contrast T1- and 
T2-weighted MR images may be obtained at multiple stations as needed. 
A localizer MRI scan will be performed at 45 minutes after injection of 3 to 7 mCi of 68Ga-PSMA11 
(or 68Ga-RM2, depending on randomization)  to define the table positions.  After correct positioning 
of the spatial acquisition windows is ensured, the combined PET/MRI acquisition will be initiated 
with 3 to 5 table positions at a 2 to 4 min acquisition time per table position.  Only MR sequences 
required for attenuation correction of PET data will be acquired. 
Participants will be randomized to have 68Ga-RM2 first followed by 68Ga-PSMA11 within 2 weeks or 
68Ga-PSMA11 first followed by 68Ga-RM2 within 2 weeks (50/50 chance for each schedule). 
The above will be repeated approximately 6 months after HDR local treatment. 
5.3 Image interpretation 
The PET/MRI scans will be interpreted by ABNM certified Nuclear Medicine physicians and ABR 
certified Radiologists.  Drs Iagaru, Davidzon, Loening and Vasanawala have significant clinical 
experience and will be blinded to the participants’ medical history and the results of other imaging 
modalities.  Consensus read will be obtained for each scan.  Each lesion will be tabulated and a 
comparison of lesion detection by each tracer will be conducted. 
The study team will communicate the results of the scans to the referring (treating) physicians. 
6. STUDY PROCEDURES  
6.1 Pre-Study 
Potential subjects will be referred by treating physicians for participation in this imaging study.  The 
following procedures will occur pre-study: 
• 
Review of eligibility criteria 
• 
Obtain informed consent 
• 
Collect demographics 
• 
Review medical history, including any concomitant medication.   
6.2 Imaging Days 
Subjects will undergo 2 separate clinic visits not less than 3 days apart for imaging before therapy 
and two separate clinic visits for imaging after therapy.  After the 1st scan, the 2nd scan will only 
occur after the follow-up with the patient for the 1st scan, and after a minimum of 3 days have 
elapsed.  On each imaging day, subjects will receive an intravenous (IV) injection of investigational 


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imaging agent (68Ga-RM2 or 68Ga-PMSA11) and undergo PET/MRI image collection as described 
above.   
6.3 Follow-up 
Active subject participation ends after the 24 to 72 hour Safety Follow-up after the 2nd post-therapy 
scan.  Investigators will follow subjects by chart review for 12 months post-scan to record any 
standard of care biopsies or imaging results.  The investigators will assist with identification of 
lesions that can be biopsied, based on 68Ga-RM2 and/or 68Ga-PMSA11 PET/MRI findings. 
If a subject transfers clinical care outside of Stanford Healthcare during the chart review clinical 
follow-up period, investigators will request permission to contact the treating physician. 
6.4 Criteria for Removal from Study 
The Protocol Director may withdraw subjects from the study for one or more of the following 
reasons:  failure to follow the instructions of the Protocol Director and/or study staff; determination 
that continuing the participation could be harmful to the subject; the study is cancelled or other 
administrative reasons.   
6.5 Alternatives 
The alternative is to not participate in the study.  
7. STUDY CALENDAR 
 
Pre-Study 
Scan 
Date 
24 to 72 hours 
Post-Scan 
12 months 
Informed consent 
X 
 
 
 
Demographics 
X 
 
 
 
Medical history 
X 
 
 
 
68Ga-RM2 
 
X a 
 
 
68Ga-PSMA11 (≥ 3 days and ≤ 2 weeks) 
 
X a 
 
 
Follow-up call to participant (24 to 72 hours) 
 
 
X 
 
Chart review b 
 
 
 
X 
a:  Subjects will undergo either 68Ga-RM2 PET/MRI followed within 2 weeks by 68Ga-PMSA11 PET/MRI, or 
68Ga-PMSA11 PET/MRI followed within 2 weeks by 68Ga-RM2 PET/MRI.  After the 1st scan, the 2nd scan 
will only occur after the follow-up with the patient for the 1st scan, and after a minimum of 3 days have 
elapsed.  This will be repeated approximately 6 months after HDR local treatment, prior to standard of care 
biopsy to evaluate for residual disease in the prostate. 
b:  Subjects will be followed by chart review for 24 months from initial scan date.  If a subject transfers clinical 
care from Stanford HealthCare, investigators may request records from the treating physician.  


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8. ADVERSE EVENTS AND REPORTING PROCEDURES 
8.1 Potential Adverse Events 
The administration of the radioactive substance will feel like a slight pinprick when given by 
IV injection.  Patients who are claustrophobic may feel some anxiety while positioned in the 
scanner.  Also, some patients find it uncomfortable to hold one position for more than a 
few minutes.  The subjects will not feel anything related to the radioactivity of the substance in their 
body.  Because the radioactivity is very short-lived, the radiation exposure is low.  The substance 
amount is so small that it does not affect the normal processes of the body.  
This research study involves exposure to radiation from two (before and after treatment) 
68Ga-PSMA-11 PET/MRI.  There is no radiation exposure from MRI.  The effective dose from one 
typical maximum of 259 mBq (range:  3 to 7 mCi) administration of 68Ga-PSMA-11 is 6.68 mSv.  
Therefore, the effective dose from two 68Ga-PSMA-11 PET/MRI is 13.36 mSv, approximately equal 
to 26% of the limit that radiation workers (eg, a hospital X-ray technician) are allowed to receive in 
one year.  
This research study also involves exposure to radiation from two (before and after treatment) 
68Ga-RM2 PET/MRI.  There is no radiation exposure from MRI.  The amount of radiation from one 
administration of 140 mBq of 68Ga-RM2 is 4.76 mSv.  Therefore, the effective dose from two 
68Ga-RM2 PET/MRI is 9.52 mSv, approximately equal to 20% of the limit that radiation workers 
(for example, a hospital X-ray technician) are allowed to receive in one year.  
8.2 Adverse Event Reporting 
We do not anticipate hazardous situations for the subjects as a result of this protocol.  However, 
standard of care procedures will be in place for verification of correct radiopharmaceutical dose and 
route of administration.  The study Principal Investigator (PI) or his designee will report all serious 
adverse events (per 21CFR§312.32) to the Stanford CCTO Safety Coordinator within 
10 working days of becoming aware of the event (5 days if the event is life-threatening or resulted in 
death) using the Adverse Events Communication Form.  If the principal investigator determines the 
unanticipated adverse effect presents an unreasonable risk to subjects, the study will be terminated 
as soon as possible, but no later than 5 working days after the PI makes the determination and no 
later than 15 working days after first receiving notification of the effect.  
9. REGULATORY CONSIDERATIONS 
9.1 Institutional Review of Protocol 
The protocol, the proposed informed consent and all forms of participant information related to the 
study (eg, advertisements used to recruit participants) will be reviewed and approved by the 
Stanford IRB.  Any changes made to the protocol will be submitted as a modification and will be 
approved by the IRB prior to implementation.  The Protocol Director will disseminate the protocol 
amendment information to all participating investigators.  
9.2 Data Management Plan 
The CRFs will be stored in a locked office in the Nuclear Medicine clinic.  Records will be kept using 
OnCore.  
During the clinical investigation, the Protocol Director will evaluate the progress of the trial, including 
periodic assessments of data quality and timeliness, participant recruitment, accrual and retention, 
participant risk versus benefit, performance of trial sites, and other factors that can affect study 


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outcome.  Monitoring of the trial will occur every 8 weeks and a record of monitoring activities will 
be maintained by the study team.  
The Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) will audit study 
related activities to determine whether the study has been conducted in accordance with the 
protocol, local standard operating procedures, FDA regulations, and Good Clinical Practice (GCP).  
This may include review of regulatory binders, case report forms, eligibility checklists, and source 
documents.  In addition, the DSMC will regularly review serious adverse events and protocol 
deviations associated with the research to ensure the protection of human subjects.  Results of 
DSMC audits will be communicated to the IRB and the appropriate regulatory authorities at the time 
of continuing review, or in an expedited fashion, as needed.  
10. Statistical Considerations and Evaluation of Results 
10.1 Aim 1 
Participants: 100 patients with low- or intermediate-risk prostate cancer, as described in the 
inclusion/exclusion criteria. 
Design: Patients will have both 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI, including mpMRI. mpMRI 
and PET images will each be evaluated separately. For each of the 12 prostate regions, between 1-
3 imaging-positive samples will be taken, and 1 sample will be taken from each imaging-negative 
region. 
Outcome measures: Number and location of lesions will be recorded for each modality in each 
patient. Gold standard will be based on the biopsy of lesions found on 68Ga-RM2 and 68Ga-PSMA-
11 PET and prior systematic prostate biopsy, including IHC stains for GRPr and PSMA. 
Hypothesis: 68Ga-RM2 and 68Ga-PSMA-11 PET/MRI sensitivity, either alone or in combination, will 
be higher than that of mpMRI alone. 
Reference standard: disease status of a lesion will be defined by biopsy of lesions found on 68Ga-
RM2 and 68Ga-PSMA-11 PET and from prior saturation prostate biopsy. Tissue samples will be 
evaluated for GRPr and PSMA 
expression 
as 
previously
reported [1, 2] and results will 
be 
compared 
to 
imaging
findings. For GRPr staining, 
immunohistochemistry will be 
performed 
using 
standard
protocols with primary rabbit 
polyclonal 
antibody 
(OPA1-
15619, 1:200 dilution; Affinity 
Bioreagents, 
Golden,
Colorado). For PSMA, a rabbit 
polyclonal anti-PSMA antibody 
(D7I8E; 
Cell 
Signaling 
technology, 
#12815, 
1:100
dilution) we be used following 
the 
manufacturer's 
immunohistochemistry protocol. 
We already successfully used 


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Protocol version 12 July 2019 
these, as shown on page 11. 
Drs. Kunder (clinical pathologist), Stoyanova and Dalm will perform all histopathological analyses. 
Clinical follow-up will be gold standard if biopsy cannot be done. 
Test to be evaluated: All T1w, T2w, DWI and DCE 
MR images will first be analyzed and graded by two-
board 
certified 
abdominal 
radiologists 
with 
subspecialty training in body MRI and extensive 
clinical experience in prostate MRI (Drs. Loening 
and Vasanawala) using the PI-RADS version 2 
scoring system, blinded to the clinical information 
and pathology. The PET images will be corrected 
using the attenuation data from the MRI scan, and 
Drs. Iagaru and Davizon who already have extensive 
experience with 68Ga-RM2 and 68Ga-PSMA-11 from 
our clinical trials, will perform blinded and random 
interpretation of the PET scans. Areas of focally 
increased 
68Ga-RM2 and 
68Ga-PSMA-11 uptake 
above surrounding background will be considered 
positive for PC (Figures 9 and 10). This approach is 
based on recently published guidelines for standard 
image interpretation developed for 68Ga-PSMA-11 
image 
interpretation 
[90]. 
In 
addition, 
semi-
quantitative measurements of tracer uptake (SUVmax) 
will be recorded for each lesion. 
 
Statistical Analysis: The following statistical considerations have the full support of a 
biostatistician (Dr. Jarrett Rosenberg) within the Department of Radiology, who has been 
specifically assigned to the project and can provide continuous support throughout the data 
collection and data analysis process. He has also carefully reviewed the study design and was fully 
involved in the writing of this grant proposal. 
Because there may be multiple lesions per-patient and an indefinite number of non-lesions, the 
primary analysis will be per-region. Each of the 12 regions will have gold-standard positive or 
negative information, as well as imaging positive or negative assessments. Predictive accuracy of 
PI-RADS composite score (mpMRI) and SUVmax PET uptake values will be assessed by ROC 
analysis using univariable logistic regression for the presence of PC. Areas under the entire ROC 
curve, and partial area at fixed 90% specificity will be compared. Additional benefit of the other 
modalities over mpMRI alone will be tested by a multivariable logistic regression. All analyses will 
be adjusted for clustering within patient. 
Statistical Power and Sample Size: Based on our clinical experience at Stanford, we expect an 
average of 2 PC-positive regions and 10 PC-negative regions per patient. Assuming mpMRI has 
sensitivity of 80% and specificity of 80-90% [91], a sample size of 1200 regions with 20% 
prevalence will provide 90% power at 5% error to demonstrate non-inferiority of a PET sensitivity of 
90% at 80-90% specificity [62, 92, 93]. 
The per-lesion analysis will depend on the number of lesions found but will be similar. We will also 
explore whether specific imaging findings are especially accurate in detection of specific subtypes 
of PC or prostate regions (i.e., peripheral versus transitional zones). It may also be the case that 


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predictive failures in imaging may be associated with a particular subtype. Given the small sample, 
we acknowledge that this analysis will be exploratory. 
10.2 Aim 2 
Participants: Those enrolled in Aim 1. 
Design: Patients will be scanned with both 68Ga-RM2 PET/MRI and 68Ga-PSMA-11 PET/MRI at six 
months after initiation of therapy. MRI and PET images will each be evaluated separately. 
Outcome measures: Changes in MRI features and/or changes in radiopharmaceutical uptake in 
lesions will be recorded for each modality in each patient. Gold standard of response to treatment 
and of PFS will be based on standard clinical follow-up (PSA, imaging, tissue diagnosis including 
IHC stains for GRPr and PSMA) 
Test to be evaluated: All T1w, T2w, DWI and DCE MR images will first be analyzed and graded by 
two-board certified abdominal radiologists with subspecialty training in body MRI and extensive 
clinical experience in prostate MRI (Drs. Loening and Vasanawala), before and after treatment. 
Areas of focally increased 68Ga-RM2 or 68Ga-PSMA-11 uptake above surrounding background on 
pre-therapy scans will be evaluated for changes in uptake by Drs. Davidzon and Iagaru. 
Hypotheses 
Primary: Change in 68Ga-RM2 or 68Ga-PSMA-11 uptake from baseline (T0) to 6 months after start 
of treatment (T1) will predict treatment response better than T0-T1 changes in MRI. 
Secondary: T0-T1 change in 68Ga-RM2 or 68Ga-PSMA-11 uptake will predict progression-free 
survival (PFS) better than MRI. 
Statistical Analysis:  
Primary: (a) logistic regression of response/non-response at T6 on T1-T0 change in PET/MRI 
measures; (b) McNemar tests of MRI and PET predictions of T6 response. 
Secondary: (a) log-rank tests of PFS time (length of drug response) on patients dichotomized as 
above/below the median change in PET/MRI measures; (b) Cox proportional-hazards regressions 
of PFS on amount of T1-T0 change in PET/MRI measures. 
Statistical Power and Sample Size: We expect a 70-80% response rate to treatment, and 20% of 
responders progressing by two years. 
A sample size of ~75 responders and ~25 non-responders will provide 90% power at one-sided 5% 
error to detect sensitivity low as 80% at fixed 90% specificity, and to demonstrate a difference in 
sensitivities of 10 percentage points (e.g., 80% vs 90%). 
Median-change groups of ~40 each among the responders will provide 90% power at one-sided 5% 
error to detect differences in PFS hazard ratios as small as 2.5.  
10.3 Study Outcomes (ClinicalTrials.gov) 
Primary Outcomes 
Title:  68Ga-RM2 and 68Ga-PSMA-11 PET/MRI can detect additional cancers over mpMRI   
Description:  Detection of PC lesions will be assessed by 68Ga-PSMA-11 and 68Ga-RM2 
PET scans.  The outcome is the number of participants without dispersion, by randomization 
schedule, for which an assessment of PET-based PC lesions is successfully obtained.  
Timeframe:  60 months  
Safety outcome:  No  


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Title:  68Ga-RM2 and 68Ga-PSMA-11 PET/MRI can assess changes in response to 
treatment and predict PFS at 24 months   
Description:  Therapeutic response to HDR will be assessed by 68Ga-PSMA-11 and 
68Ga-RM2 PET scans.  The outcome is the number of participants without dispersion, by 
randomization schedule, for which an assessment of PET-based therapeutic response to 
HDR is successfully obtained.  
Timeframe:  84 months  
Safety outcome:  No  
Secondary Outcome 
None.  
 
10.4 Accrual estimates 
We expect the accrual of 20 patients each year for 5 years.  This is achievable given our 
experience with other protocols and the support from the referring physicians, Drs Buyyounouski, 
Bagshaw and Hancock who run the HDR Brachytherapy Clinic at the Stanford Cancer Institute.   
Potential difficulties and limitations: All patients will first be seen by a Stanford Cancer Institute 
physician and then referred if 
appropriate on clinical grounds 
for this study. SCI has a 
substantial volume of men with 
PC. We do not anticipate any 
difficulty in recruiting 100 men 
at Stanford with PC over the 
period 
of 
the 
grant 
since 
referring 
physicians 
from 
Radiation 
Oncology 
are 
supporting 
the 
study. 
We 
previously enrolled 10 patients 
included in a prior PET/MRI 
pilot study in less than 2 
months.  
Based 
on 
our 
preliminary 
experience in patients with PC 
we do not expect any technical 
problems. We already hold 
FDA-approved INDs for 68Ga-
RM2 PET imaging (IND # 
) and 
68Ga-PSMA-11 
PET imaging (IND # 128379). 
We have already imaged 38 PC 
patients 
at 
initial 
diagnosis 


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(n=9) or BCR (n=29) with both 68Ga-RM2 PET and 68Ga-PSMA-11 PET. Therefore, we do not 
anticipate problems enrolling participants in this study. 
Lastly, we successfully tested in-house the PSMA and GRPr IHC stains both in benign prostate 
tissue and PC, as shown in Figure 11. Therefore, we do not anticipate issues with the IHC 
analyses of tissue samples from the enrolled participants. 


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imaging. Cancer Biother Radiopharm. 2012;27:65-71. doi:10.1089/cbr.2011.1061. 
89. 
Kähkönen E, Jambor I, Kemppainen J, Lehtiö K, Grönroos TJ, Kuisma A, et al. In Vivo 
Imaging of Prostate Cancer Using [68Ga]-Labeled Bombesin Analog BAY86-7548. Clinical Cancer 
Research. 2013;19:5434-43. doi:10.1158/1078-0432.ccr-12-3490. 
90. 
Fanti S, Minozzi S, Morigi JJ, Giesel F, Ceci F, Uprimny C, et al. Development of 
standardized image interpretation for 68Ga-PSMA PET/CT to detect prostate cancer recurrent 
lesions. Eur J Nucl Med Mol Imaging. 2017;44:1622-35. doi:10.1007/s00259-017-3725-1. 
91. 
Turkbey B, Brown AM, Sankineni S, Wood BJ, Pinto PA, Choyke PL. Multiparametric 
prostate magnetic resonance imaging in the evaluation of prostate cancer. CA Cancer J Clin. 
2016;66:326-36. doi:10.3322/caac.21333. 
92. 
Zamboglou C, Drendel V, Jilg CA, Rischke HC, Beck TI, Schultze-Seemann W, et al. 
Comparison of 68Ga-HBED-CC PSMA-PET/CT and multiparametric MRI for gross tumour volume 
detection in patients with primary prostate cancer based on slice by slice comparison with 
histopathology. Theranostics. 2017;7:228-37. doi:10.7150/thno.16638. 
93. 
Kesch C, Vinsensia M, Radtke JP, Schlemmer HP, Heller M, Ellert E, et al. Intra-individual 
comparison of 18F-PSMA-1007-PET/CT, multi-parametric MRI and radical prostatectomy specimen 
in patients with primary prostate cancer - a retrospective, proof of concept study. Journal of nuclear 
medicine : official publication, Society of Nuclear Medicine. 2017. doi:10.2967/jnumed.116.189233. 
 


IRB-51987 
Page 34 of 35 
CONFIDENTIAL 
Protocol version 12 July 2019 
Inclusion/Exclusion Criteria Checklist 
Protocol Title: 
Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate 
Cancer Scheduled for High-Dose Rate Brachytherapy Using 68Ga-RM2 
PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
Protocol Number: 
IRB-51987  /  SRC-TBD  
Principal Investigator: 
Andrei Iagaru, MD 
3.1 Inclusion Criteria 
Inclusion Criteria  
Yes must be checked to be eligible 
Yes 
No 
Supporting 
Documentation 
1. Patients must be at least 18 years of age 
☐ 
☐ 
 
2. Patients must be able to provide informed consent 
☐ 
☐ 
 
3. Histologically proven low-grade or intermediate-
grade PC 
☐ 
☐ 
 
4. Scheduled to undergo targeted local therapy (HDR 
brachytherapy) 
☐ 
☐ 
 
3.2 Exclusion Criteria 
Exclusion Criteria  
No must be checked to be eligible 
Yes 
No 
Supporting 
Documentation 
1. Inability to lie still for the entire imaging time 
☐ 
☐ 
 
2. Inability to complete the needed investigational and 
standard-of-care imaging examinations due to other 
reasons (severe claustrophobia, radiation phobia, 
etc.) 
☐ 
☐ 
 
3. Any additional medical condition, serious 
intercurrent illness, or other extenuating 
circumstance that, in the opinion of the Investigator, 
may significantly interfere with study compliance 
☐ 
☐ 
 
4. Metallic implants (contraindicated for MRI) 
☐ 
☐ 
 
*All subject files must include supporting documentation to confirm subject eligibility.  The method of 
confirmation can include, but is not limited to, laboratory test results, radiology test results, subject 
self-report, and medical record review.   


IRB-51987 
Page 35 of 35 
CONFIDENTIAL 
Protocol version 12 July 2019 
Statement of Eligibility 
By signing this form of this trial I verify that this subject is [☐eligible / ☐ ineligible] for participation 
in the study.  This study is approved by the Stanford Cancer Institute Scientific Review Committee, 
the Stanford IRB, and has finalized financial and contractual agreements as required by Stanford 
School of Medicine’s Research Management Group.   
Treating Physician Signature: 
Date: 
Printed Name: 
 
 
Study Coordinator Signature: 
Date: 
Printed Name: 
 
Secondary Reviewer Signature: 
Date: 
Printed Name: 

ICF_002.pdf: 
 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 1 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
Are you participating in any other research studies? _____ Yes _____No 
 
INTRODUCTION TO RESEARCH STUDIES 
You are invited to participate in a research study of investigational imaging agents 
68Ga-RM2 and 68Ga-PMSA11 being conducted by Andrei H Iagaru, MD, at the Stanford 
Cancer Center. You were selected as a possible participant in this study because you 
are suspected to have prostate cancer and are scheduled to have prostate biopsy. 
 
This document is to be used as a guide for a discussion between you and your Study 
Doctor and the study team. This form, called an informed consent document, was 
designed to help you understand why this study is being done; what part of the study is 
“research” or “experimental;” what will be asked of you if you choose to participate; 
possible risks; any inconveniences or discomforts you may experience; and other 
important information. This document is intended to provide the information that a 
potential participant might want to have in order to make an informed decision about 
whether to participate in the research study. If you have any questions or would like 
additional information, please ask the person obtaining consent or any other member of 
the study team. 
 
If you choose to participate, this form may also be helpful as a reference or reminder 
about your role in the study, and whom to contact if you have any questions at any time 
during your participation. If you wish, you can also discuss this study and your role with 
your family doctor or medical provider. 
 
• This consent is sought for research and your participation is voluntary. 
• The goal of this research project is to evaluate a new way to assess response to 
treatment. Your participation is expected to take approximately 2-3 weeks of 
active participation before treatment and another 2-3 weeks approximately 6 
months after treatment. 
• There are risks associated with the administration of radioactive materials. This 
amount of radiation involves minimal risk and is necessary to obtain the research 
information desired. 
• We cannot and do not guarantee or promise that you will receive any benefits 
from this study. 
• Your participation can help researchers develop new tools to better monitor or 
diagnose disease in the future.  
• You will not feel any different while participating in this study. 
• Your decision not to participate will not have any negative effect on you or your 
medical care. You can decide to participate now, but withdraw your consent later 
and stop being in the study without any loss of benefits or medical care to which 
you are entitled. 
 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 2 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
PURPOSE OF RESEARCH 
This clinical research study hopes to find out whether the combination of imaging 
agents 68Ga-RM2 and 68Ga-PMSA11 is better at assessing response to therapy than 
standard imaging or biopsy. You were selected as a possible participant in this study 
because you are known to have prostate cancer and are scheduled to receive local 
treatment. 
 
The scans in this research study and the use of 68Ga-RM2 and 68Ga-PMSA11 for those 
scans is investigational (“experimental”). The word “investigational” means that neither 
68Ga-RM2 or 68Ga-PMSA11 are approved by the US Food and Drug Administration 
(FDA) for use in the United States. This study is being conducted under an application 
submitted to FDA, called an “Investigational New Drug Application” or “IND.”  
 
The parts of this study that are research (not part of your regular care) are the use of 
68Ga-RM2 and 68Ga-PMSA11, and the associated PET/MRI scans. 
 
If you decide to terminate your participation in this study, you should notify Dr. Iagaru at 
650-725-4711.  
 
This research study is looking for 100 people with suspected prostate cancer to 
participate. Stanford University is the only location enrolling research study participants.  
 
VOLUNTARY PARTICIPATION 
Your participation in this study is entirely voluntary. Your decision not to participate will 
not have any negative effect on you or your medical care. You can decide to participate 
now, but withdraw your consent later and stop being in the study without any loss of 
benefits or medical care to which you are entitled. 
 
DURATION OF STUDY INVOLVEMENT  
Your participation in this research study is expected to take approximately 2-3 weeks of 
active participation before treatment and another 2-3 weeks approximately 6 months 
after treatment. The 68Ga-RM2 and 68Ga-PMSA11 scans will be done within 2 weeks of 
each other. You will be contacted by research staff 1-3 days after each scan to see how 
you are feeling. Study investigators will monitor your medical record for 12 months after 
your last scan, but you are not required to come to clinic for any study visits during 
follow-up. 
 
PROCEDURES 
If you are eligible and choose to participate, the Study Doctor and his research study 
staff will perform the following procedures: 
 
 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 3 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
Pre-Study 
• Review this informed consent form with you and ask you to sign. 
• Collect demographic information (age, gender, race, etc.) 
• Review your medical history 
• You will be assigned randomly to receive either (equal chance of either option) 
o 
68Ga-RM2 PET/MRI followed within 2 weeks by 68Ga-PMSA11 PET/MRI 
OR 
o 
68Ga-PMSA11 PET/MRI followed within 2 weeks by 68Ga-RM2 PET/MRI 
before and after treatment 
 
Imaging Days 
You will come to the clinic twice to receive an investigational imaging agent (68Ga-RM2 
or 68Ga-PMSA11) and undergo PET/MRI imaging. The procedures are very similar for 
each imaging agent, and include: 
• You will be asked to drink 1-2 glasses of water before you arrive at clinic. 
• Record your vital signs (which includes your heart rate and blood pressure,) 
• The radiolabeled investigational imaging agent will be administered through a 
needle in your vein 
• You will be asked to pee immediately before image collection 
• Approximately 45 minutes after administration of 68Ga-RM2 or 45 minutes after 
administration of 68Ga-PMSA11, PET/MRI image collection will begin. 
o During image collection, study personnel will collect both PET images, 
which detect the small amount of radiolabeled imaging agent, and MR 
images, which use strong magnetic fields, to look at your tissues and 
organs.  
• Record vital signs after image collection is complete 
 
Your study doctor or research staff will contact you by phone 24-72 hours post-scan to 
ask how you are feeling.  
 
The above will be repeated approximately 6 months after treatment. 
 
Information about the medical scans 
 
Magnetic Resonance Imaging (MRI):  An MRI does not require a radiation exposure. 
The scan will take about 30 to 60 minutes. The MRI scan evaluates blood flow and the 
extent of the cancer. An MRI scanner is large, tunnel shaped machine, and uses a 
strong magnet and radiofrequency magnetic fields to make images of the body interior. 
This magnet is very strong, and will attract or pull on some metals and affect some 
electronic devices, including magnetic access cards, and the magnetic strip on credit / 
debit /ID cards. Do not bring any metal objects into the magnet room. Any metal objects 
that you are carrying or have in your body could be a hazard to you or others. Watches; 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 4 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
hearing aids or other removable medical devices; jewelry / rings; credit / debit /ID cards; 
access cards; should be removed. You will be provided a way to secure these items. 
Because the magnetic field is so strong, tell the study team now, and also tell the MRI 
operator before entering the MRI room, if any of the following apply to you.  
 
The scanning procedure is very much like an X-ray, but uses a strong magnetic field 
instead of X-rays. You will not be able to feel the magnetic field. You will be asked to lie 
on a long narrow bench for up to 60 minutes while the machine performs the scan. You 
will be asked not to move during the scan and to relax and breathe normally. During this 
time, you will not be exposed to X-rays, but rather the magnetic field. During the scan, 
the bench you are lying on will move into a narrow space in the scanner. Many steps 
have been taken to make the procedure comfortable, but you may still experience some 
discomfort or anxiety ("claustrophobia”) from being in this confined space. The scanner 
will make repetitive tapping noises, which can seem very loud inside the scanner. You 
may be provided with earplugs or headphones to wear.  
 
Dizziness or upset stomach (nausea) may occur if you move your head rapidly within 
the magnet.  
 
Some parts of the MRI machine (radio frequency imaging coils and imaging software) 
that will be used have not been approved by FDA, but are similar to parts that have 
been approved by the FDA.  
 
IF YOU FEEL DISCOMFORT AT ANY TIME, NOTIFY THE OPERATOR AND YOU 
CAN DISCONTINUE THE EXAM AT ANY TIME.  
 
The scans performed in this study are for specific research purposes and are not 
optimized to find medical abnormalities. The investigators for this project may not be 
trained to perform medical diagnosis. The investigators and Stanford are not 
responsible for failure to find existing abnormalities with these MRI scans. However, on 
occasion the investigator may notice a finding on an MRI scan that seems abnormal. 
When this occurs, a physician will be consulted as to whether the findings merit further 
investigation, in which case the investigator will contact you and your primary care 
physician and inform you of the finding. The decision as to whether to proceed with 
further examination or treatment lies solely with you and your physician. The 
investigators, the consulting physician, and Stanford are not responsible for any 
examination or treatment that you undertake based on these findings. Because the 
images collected in this study may not comprise a proper clinical MRI scan, these 
images will not be made available for diagnostic purposes.  
 
A positron emission tomography (PET) scan will be performed according to standard 
practice as part of the medical scan. A PET scan is a computerized image that looks at 
blood flow and the extent and activity of the cancer in your entire body. PET scans use 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 5 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
a radioactive material called a “radio isotope;” “radio tracer;” or “radiolabel.”  A 
tourniquet will be applied to your arm or leg to help find a vein, and a small amount of a 
radioactive tracer (68Ga-RM2 and 68Ga-PMSA11) will be injected into a vein about 1 
hour before the scan. The radiolabel accumulates in areas of the body that are 
metabolically active, and this accumulation is detected by the scanner. Tumors are 
usually very metabolically active, more so than normal tissues. You will be asked to lie 
on a long narrow bench for up to 60 minutes while the machine performs the scan. You 
will be asked to not eat or drink anything but water (i.e., “fast”) for about 4 to 6 hours 
before the scan. The entire procedure will take about 30 to 60 minutes. You may 
experience some discomfort or anxiety from being in the confined space. If you become 
anxious or concerned in tight spaces, or from loud noises, tell the study team or 
technician before the scan.  The camera will record the tracer’s signal as it travels 
through your body. 
 
Routine Clinical Follow-Up 
Once study staff contact you after your second scan after treatment, your active 
participation in this clinical research study is complete. However, the Study Doctor and 
research study staff will continue to monitor your medical record to record the results of 
any biopsies or imaging scans performed as part of your standard medical care. This 
information is needed for investigators to study whether lesions detected by 68Ga-RM2 
or 68Ga-PMSA11 are later confirmed to be malignant and if the treatment worked. 
Investigators will monitor your medical record for 12 months after the last image is 
collected. 
 
If you transfer your regular medical care to outside Stanford during this 12 months chart 
review, study staff will contact you to get your permission to access medical records 
from your new treating physician. 
 
Any of your samples (images) which are used in research may result in new products, 
tests or discoveries. In some instances, these may have potential commercial value and 
may be developed and owned by the Investigators, Stanford University and/or others. 
However, donors of samples do not retain any property rights to the materials. 
Therefore, you would not share in any financial benefits from these products, tests or 
discoveries. 
 
Future Use of Private Information and/or Specimens 
Research using private information and/or specimens is an important way to try to 
understand human disease.  You are being given this information because the 
investigators want to save private information and/or specimens for future research.   
 
Identifiers might be removed from identifiable private information and/or identifiable 
specimens and, after such removal, the information and/or specimens could be used for 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 6 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
future research studies or distributed to another investigator for future research studies 
without additional informed consent from you. 
 
Adverse event monitoring will be performed as part of the procedures described 
above. During the treatment period, the Study Doctors will monitor you for any potential 
side effects.   
 
If, at any time, you have any symptom; side effect; or injury affecting you physically or 
mentally during the study, you should tell the Study Doctors or nurses right away, 
even if you do not think it was caused by the study treatment.  
 
If you have to go to the hospital for any reason, please tell the hospital staff that you are 
participating on a research study, and give them the contact information for the 
study team.  
 
PARTICIPANT RESPONSIBILITIES 
As a participant, your responsibilities include:  
• Follow the instructions of the Study Doctor and study staff. 
• Keep your study appointments. If it is necessary to miss an appointment, please 
contact the Study Doctor or research study staff to reschedule as soon as you 
know you will miss the appointment. 
• Tell the Study Doctor or research study staff about any side effects, doctor visits, 
or hospitalizations that you may have. 
• Tell the Study Doctor or research staff if you believe you might have gotten your 
partner pregnant. 
• Ask questions as you think of them. 
• Tell the Study Doctor or research staff if you change your mind about staying in 
the study. 
• This study has magnetic resonance imaging (MRI) scans that are required. Tell 
the Study Team or the MRI operator if you have any tattoos on your body, 
including eyeliner and other permanent makeup. 
 
WITHDRAWAL FROM STUDY 
If you first agree to participate and then you change your mind, you are free to withdraw 
your consent and discontinue your participation at any time. Your decision will not affect 
your ability to receive medical care for your disease and you will not lose any benefits to 
which you would otherwise be entitled.  
 
If you decide to withdraw your consent to participate in this study, you should notify Dr. 
Iagaru at 650-725-4711. 
 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 7 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
If you withdraw from the study, or the investigational imaging agent administration is 
stopped for any reason, study staff will request permission to contact you 24-72 hours 
after investigational imaging agent administration to check on how you are feeling. You 
will not be required to return to clinic. 
 
If you choose to withdraw from the study after undergoing one image collection, study 
staff will request your permission to continue monitoring your medical record for results 
from clinical biopsies and image collection, as outlined above. Please tell Dr. Iagaru if 
you also wish to withdraw from the medical chart review. 
 
The Study Doctor may also withdraw you from the study without your consent for one or 
more of the following reasons:   
• Failure to follow the instructions of the Protocol Director and study staff. 
• The study doctor decides that continuing your participation could be harmful to 
you, or otherwise not in your best interest. 
• Pregnancy  
• The study is cancelled.  
• Other administrative reasons. 
• Unanticipated circumstances. 
 
POSSIBLE RISKS, DISCOMFORTS, AND INCONVENIENCES  
There are risks, discomforts, and inconveniences associated with any research study. 
This section describes the reasonably foreseeable risks; discomforts; and 
inconveniences that you may experience. In addition, because this is a research study, 
there may be risks that are not yet known (“unforeseeable”). These deserve careful 
thought. You should talk with the Study Doctor if you have any questions.  
 
You must tell the Study Doctor or study team about all side effects that you have. If you 
are not honest about your side effects, it may not be safe for you to stay in the study. 
Your Study Doctor may give you medications to try to help lessen some of the side 
effects. All patients in the study will be monitored for side effects.  
 
If you experience serious problems, you may be asked to return to the study center for 
more tests. If you experience the following symptoms of an allergic reaction, contact the 
Study Doctor or the Study Team immediately.  
• Allergic reaction, including rash, hives, or blisters; increased heart rate (a fast 
pulse or tachycardia); or abnormal or increased sweating  
• Swelling of the face, mouth, lips, gums, tongue or neck 
• Wheezing or difficulty breathing  
• Dizziness and fainting 
 
 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 8 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
Possible Risks from 68Ga-RM2 or 68Ga-PMSA11 
The amount of targeting agent (RM2 or PMSA11) is so small that it does not affect body 
processes. We previously used 68Ga-RM2 and 68Ga-PMSA11 in patients with prostate 
cancer and no adverse events were recorded.  
 
Possible Risks from Procedures 
There are other risks and possible discomforts you might experience from the study 
procedures. The following discusses procedure risks related only to the research, and 
does not include risks of procedures that should be discussed as part of your regular 
medical care.  
 
Test results:   
• May indicate that you have another disease or condition that you were not aware 
of. This may be concerning to you, and cause anxiety or other feelings. 
• Rarely, may not be correct.  
o A false negative is a test result that indicate a person does not have a 
condition, but they really do. 
o A false positive is a test result that indicates a person has a condition, but 
they really don’t. 
o Incorrect results can cause as much concern and anxiety as a correct 
diagnosis.  
• May become known to others, which may affect their judgment of you.  
 
Intravenous Injection:  You may experience some temporary discomfort, bleeding, 
bruising, or rarely, infection, at the site of a needle stick. 
 
Radiation Risk:   You will be exposed to radiation during this research from 68Ga PSMA 
11 and 68Ga RM2. This radiation exposure is not necessary for your medical care and 
is for research purposes only. The additional amount of radiation exposure is about 23 
mSv, which is approximately equal to 46% of the limit that radiation workers (for 
example, a hospital x-ray technician) are allowed to receive in one year. This amount of 
radiation involves minimal risk and is necessary to obtain the research information 
desired. 
 
MRI (Magnetic Resonance Imaging – Part of the PET/MRI Scans) Risks: 
Magnetic fields do not cause harmful effects at the levels used in the MRI machine. 
However, the MR scanner uses a very strong magnet that will attract some metals and 
affect some electronic devices. Exposure of the following to MRI magnetic fields may 
cause harm to you or others. 
• If you have a cardiac pacemaker or any other biomedical device in or on your 
body, it is very important that you tell the operator/investigator immediately, these 
devices could malfunction when exposed to the very strong magnetic field.  


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 9 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
• As metallic objects may experience a strong attraction to the magnet, it is also 
very important that you notify the operator of any metal objects (metal plate; pin; 
screws; surgical clips; metallic fragments), devices (including hearing aids), or 
implants that are in or on your body before entering the magnet room. These 
pieces of metal could move while in your body, causing possible serious injury or 
death 
• If you have any tattoos on your body, including eyeliner and other permanent 
makeup they could become warm and irritated during the scan and remain so for 
several days. If you would prefer not to participate in the MR scan due to the 
presence of tattoos on your body, please inform a research team member. 
 
All metal objects must be removed (if possible) before entering the magnet room. In 
some cases, having those devices means you should not have an MRI scan performed. 
In addition, watches and credit cards should also be removed as these could be 
damaged. You will be provided a way to secure these items. If you have any history of 
head or eye injury involving metal fragments, if you have ever worked in a metal shop, if 
you have, or previously had kidney problems, or if you could be pregnant, this may 
mean you should not have an MRI scan performed. You should notify the 
operator/investigator of any of these events.  
 
When you are in the MRI scanner, you may experience discomfort or anxiety due to be 
in the small space inside the machine, or from the loud noises the MRI scanner makes.  
Dizziness or upset stomach (nausea) may occur if you move your head rapidly within 
the magnet.  
 
There is a possibility that you will experience a localized twitching sensation due to the 
magnetic field changes during the scan. This is not unexpected and should not be 
painful. However, you may have the scan stopped at any time if this occurs. 
 
Some of the radio frequency imaging coils, imaging software and devices being used in 
your scan are not approved by the FDA but are similar to counterparts that have been 
approved by the FDA. There is a small risk of heating from the cables associated with 
these devices. Please report any heating sensation immediately. 
 
The scans performed in this study are for specific research purposes and are not 
optimized to find medical abnormalities. The investigators for this project may not be 
trained to perform medical diagnosis. The investigators and Stanford are not 
responsible for failure to find existing abnormalities with these MRI scans. However, on 
occasion the investigator may notice a finding on an MRI scan that seems abnormal. 
When this occurs, a physician will be consulted as to whether the findings merit further 
investigation, in which case the investigator will contact you and your primary care 
physician and inform you of the finding. The decision as to whether to proceed with 
further examination or treatment lies solely with you and your physician. The 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 10 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
investigators, the consulting physician, and Stanford are not responsible for any 
examination or treatment that you undertake based on these findings. Because the 
images collected in this study may not comprise a proper clinical MRI scan, these 
images will not be made available for diagnostic purposes. 
 
PET scans (part of the PET/MRI scans) Risk:  A PET scan exposes you to a small dose 
of radiation (discussed above). When you are in the PET scanner, you may experience 
discomfort or anxiety due to be in the small space inside the machine, or from the loud 
noises the scanner makes. If you become anxious or concerned in tight spaces, or from 
loud noises, tell the study team or technician before the scan. 
  
Injection of radiotracers:  A radiotracer will be injected for the medical scans, such as 
PET/MRI scans. Following are the risks associated with injection of contrast agents.  
• Allergic reaction, which can be severe and/or life threatening.  
• Kidney problems or kidney failure, especially if you are taking Glucophage 
(metformin, a common medicine for diabetes).  
• After the injection, there is a risk of pain, discomfort, or a burning sensation at the 
injection site; a flushing sensation; a salty or metallic taste in the mouth; a brief 
headache; or nausea/vomiting.  
• If you are a smoker or exposed to cigarettes or nicotine, you may experience 
spasms in the arteries of your heart. 
 
Personal anxiety:  Following are some common concerns that research subjects may 
have. 
• You may be asked sensitive or private questions which you normally do not 
discuss. It may be necessary to answer some of these questions related to your 
health and medical status.  
• You may be concerned about your personal information being revealed. Although 
the Study Team, Stanford, and FDA does their best to protect your personal 
information, this can not be absolutely guaranteed.  
 
Other risks:  Since 68Ga RM2 and 68Ga PMSA11 is investigational (“experimental”), 
there may be other risks that are unknown (“unforeseeable”) at this time.  
 
It is important that you report all symptoms and side effects that you experience 
as soon as they occur, whether or not you think they are caused by 68Ga-RM2, 
68Ga-PSMA11 or study procedures. You can contact the Study Team at 650 725 
4711. If you are unable to reach anyone at the number(s) listed above, and you feel you 
may need medical attention, call 911 or go to the nearest emergency room. 
 
 
 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 11 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
POTENTIAL BENEFITS 
No treatment for prostate cancer is offered as part of this study. Your participation can 
help researchers develop new tools to better monitor or diagnose disease in the future.  
 
We cannot and do not guarantee or promise that you will receive any benefits from this 
study. 
 
ALTERNATIVES 
Your participation in the study is voluntary. The alternative is not to participate.  
If you decide that you do not wish to take part in this study and wish to pursue any of 
these, or other alternatives, this will not change your regular medical care or the other 
treatment choices in any way. 
 
PARTICIPANT’S RIGHTS 
You should not feel obligated to agree to participate. Your questions should be 
answered clearly and to your satisfaction. If you decide not to participate, tell the Study 
Doctor.  
 
You will be told of any important new information that is learned during the course of 
this research study, which might affect your condition or your willingness to continue 
participation in this study. After you hear about this information, you have the right to 
withdraw from the program. 
 
If medically relevant information about you or your test results that might affect your 
future treatment or your willingness to continue participation in this study is obtained, 
this information will be discussed with you. 
 
ClinicalTrials.gov 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as 
required by U.S. Law. This Web site will not include information that can identify you. At 
most, the Web site will include a summary of the results. You can search this Web site 
at any time. 
 
CONFIDENTIALITY 
The results of this research study may be presented at scientific or medical meetings or 
published in scientific journals. Your identity and/or your personal health information will 
not be disclosed except as authorized by you or as required by law. However, there is 
always some risk that even de-identified information might be re-identified.  
 
Your research records may be disclosed outside of Stanford, including in computer 
databases and by other electronic methods, but you will only be identified by your 
unique study identifier, and not your name. Information linking your study identifier to 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 12 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
your name will be kept in a secure location at Stanford and access will be limited to the 
Study Doctor and authorized members of the Study Team. 
 
Patient information may be provided to Federal and other regulatory agencies as 
required. The Food and Drug Administration (FDA), for example, may inspect research 
records and learn your identity if this study falls within its jurisdiction. 
 
The purpose of this research study is to obtain data or information on the safety and 
effectiveness of 68Ga-RM2 and 68Ga-PMSA11; the results will be provided to the 
sponsor, the Food and Drug Administration and other federal and regulatory agencies 
as required. 
 
CERTIFICATE OF CONFIDENTIALITY 
This research is covered by a Certificate of Confidentiality from the National Institutes of 
Health (NIH). The researchers with this Certificate may not disclose or use information, 
documents, or biospecimens that may identify you in any federal, state, or local civil, 
criminal, administrative, legislative, or other action, suit, or proceeding, or be used as 
evidence, for example, if there is a court subpoena, unless you have consented for this 
use. Information, documents, or biospecimens protected by this Certificate cannot be 
disclosed to anyone else who is not connected with the research except, if there is a 
federal, state, or local law that requires disclosure (such as to report child abuse or 
communicable diseases but not for federal, state, or local civil, criminal, administrative, 
legislative, or other proceedings, see below); if you have consented to the disclosure, 
including for your medical treatment; or if it is used for other scientific research, as 
allowed by federal regulations protecting research subjects.  
 
The Certificate cannot be used to refuse a request for information from personnel of the 
United States federal or state government agency sponsoring the project that is needed 
for auditing or program evaluation by NIH which is funding this project or for information 
that must be disclosed in order to meet the requirements of the federal Food and Drug 
Administration (FDA). You should understand that a Certificate of Confidentiality does 
not prevent you from voluntarily releasing information about yourself or your 
involvement in this research. If you want your research information released to an 
insurer, medical care provider, or any other person not connected with the research, 
you must provide consent to allow the researchers to release it.  
 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 13 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
Authorization To Use Your Health Information For 
Research Purposes 
Because information about you and your health is personal and private, it 
generally cannot be used in this research study without your written 
authorization. If you sign this form, it will provide that authorization. The 
form is intended to inform you about how your health information will be 
used or disclosed in the study. Your information will only be used in 
accordance with this authorization form and the informed consent form and 
as required or allowed by law. Please read it carefully before signing it.  
 
What is the purpose of this research study and how will my health 
information be utilized in the study? 
This is a clinical research study to evaluate the safety and efficacy of 
68Ga-RM2 and 68Ga-PMSA11, investigational imaging agents. This study 
may help the sponsor and FDA determine if 68Ga-PSMA-11 and 68Ga-RM2 
are useful as PET/MRI imaging agents for prostate cancer. Your health 
information will be used to verify the study conduct and data entry, assess 
the imaging agent accuracy, and prepare regulatory documents for 
submission to the FDA for marketing approval. Your coded information may 
also be used in research related to the imaging agents, your cancer and 
related diseases, and/or diagnostics to inform treatment. The results from 
this research study are expected to be presented at scientific or medical 
meetings or published in scientific journals. You will not be personally 
identified in the publications, although representatives of the sponsor and 
FDA and other international regulatory agencies may need to know who 
you are. 
 
Do I have to sign this authorization form? 
You do not have to sign this authorization form. But if you do not, you will 
not be able to participate in this research study. Signing the form is not a 
condition for receiving any medical care outside the study. 
 
If I sign, can I revoke it or withdraw from the research later? 
If you decide to participate, you are free to withdraw your authorization 
regarding the use and disclosure of your health information (and to 
discontinue any other participation in the study) at any time. After any 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 14 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
revocation, your health information will no longer be used or disclosed in 
the study, except to the extent that the law allows us to continue using your 
information (e.g., necessary to maintain integrity of research). If you wish to 
revoke your authorization for the research use or disclosure of your health 
information in this study, you must write to:  
Dr. Andrei Iagaru 
 
300 Pasteur Dr., Room H-2200 
 
Stanford, CA 94305-5281 
 
What Personal Information Will Be Obtained, Used or Disclosed? 
Your health information related to this study, may be used or disclosed in 
connection with this research study, including, but not limited to, your 
personal identifiers (such as name and initials, address including ZIP code, 
phone numbers, dates including date of birth, age, Social Security Number, 
medical record number (MRN); and other numbers or codes such as your 
unique study identifier that might identify you) and demographics such as 
gender, race, ethnicity. During the study researchers will also obtain 
information about your health status, lifestyle choices, personal and family 
medical history (past, present and future) and allergies; information from 
clinical care (including medical reports, laboratory tests, biopsies and 
imaging). The researchers will also get information from your medical 
record (including hospital records from the Stanford Healthcare and your 
referring physician’s records). 
 
Who May Use or Disclose the Information? 
The following parties are authorized to use and/or disclose your health 
information in connection with this research study: 
• The Protocol Director, Andrei Iagaru, MD 
• The Stanford University Administrative Panel on Human Subjects in 
Medical Research and any other unit of Stanford University as 
necessary 
• Research Staff 
 
 
 
 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 15 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
Who May Receive or Use the Information? 
The parties listed in the preceding paragraph may disclose your health 
information to the following persons and organizations for their use in 
connection with this research study:  
• NIH 
• The Office for Human Research Protections in the U.S. Department 
of Health and Human Services 
• The Food and Drug Administration 
 
Your information may be re-disclosed by the recipients described above, if 
they are not required by law to protect the privacy of the information. 
 
When will my authorization expire? 
Your authorization for the use and/or disclosure of your health information 
will end on December 31, 2068, or when the research project ends, 
whichever is earlier.  
 
 
________________________________  
 
______________ 
Signature of Adult Participant 
 
 
 
 
Date 
 
 
________________________________ 
Print Name of Adult Participant 
 
 
_______________________________                       ______________ 
Signature of Legally Authorized Representative (LAR)          Date 
(e.g., parent, guardian or conservator) 
 
 
________________________________             
 
Print Name of LAR                                         
 
 
________________________________________________________ 
LAR’s Authority to Act for Participant 
(e.g., parent, guardian or conservator) 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 16 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
FINANCIAL CONSIDERATIONS 
Costs 
If you participate in this study, the study will pay for those services, supplies, 
procedures, and care associated with the study that are not a part of your routine 
medical care. However, there may be additional costs to you. These include basic 
expenses like transportation and the personal time it will take to come to the study 
visits. You and/or your health insurance must pay for services, supplies, procedures, 
and care that are required during this study for routine medical care. You will also be 
responsible for any co-payments and/or deductibles as required by your 
insurance. Participation in this study is not a substitute for health insurance.  
 
Payment/Reimbursement 
You may be provided with reimbursement of up to $250 for your participation in this 
study for reasonable travel expenses associated with the study visits. Please ask the 
study team for more information. 
 
Payments or reimbursements may only be made to U.S. citizens, legal resident aliens, 
and those who have a work eligible visa. You may need to provide your Social Security 
Number (SSN) or equivalent (i.e., federal Taxpayer Identification Number, TIN) to 
receive payment. If your SSN/ TIN is required to receive payment, and you do not wish 
to provide your SSN/ TIN, you have the option of declining the payment.  
 
Sponsor / Funding Source 
NIH is providing financial support and/or material for this study. 
 
COMPENSATION for Research-Related Injury 
All forms of medical diagnosis and treatment – whether routine or experimental – 
involve some risk of injury. In spite of all precautions, you might develop medical 
complications from participating in this study. If such complications arise, the Study 
Doctor and the research study staff will assist you in obtaining appropriate medical 
treatment. In the event that you have an injury or illness that is directly caused by your 
participation in this study, reimbursement for all related costs of care first will be sought 
from your insurer, managed care plan, or other benefits program. You will be 
responsible for any associated co-payments or deductibles as required by your 
insurance. 
 
If costs of care related to such an injury are not covered by your insurer, managed care 
plan or other benefits program, you may be responsible for these costs. If you are 
unable to pay for such costs, the Study Doctor will assist you in applying for 
supplemental benefits and explain how to apply for patient financial assistance from the 
hospital. 
 
You do not waive any liability rights for personal injury by signing this form. 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 17 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
CONTACT INFORMATION  
Questions, Concerns, Complaints, or to Report an Injury or Side Effect :  If you 
have any questions, concerns or complaints about this research study, its procedures, 
risks and benefits, or alternative courses of treatment, you should ask the Protocol 
Director, Dr. Andrei Iagaru. You should also contact him at any time if you feel you have 
been hurt by being a part of this study. You may contact him now or later at 650-725-
4711. 
 
If you are unable to reach anyone at the number listed above, and you feel you may 
need medical attention, call or go to the nearest emergency room. 
 
Independent Contact:  If you are not satisfied with how this study is being conducted, 
or if you have any concerns, complaints, or general questions about the research or 
your rights as a participant, please contact the Stanford Institutional Review Board (IRB) 
to speak to someone independent of the research team at 650-723-5244 or toll free at 
1-866-680-2906. You can also write to the Stanford IRB, Stanford University, 1705 El 
Camino Real, Palo Alto, CA 94306. 
 
EXPERIMENTAL SUBJECT’S BILL OF RIGHTS 
As a research participant you have the following rights. These rights include but are not 
limited to the participant's right to: 
• 
be informed of the nature and purpose of the experiment;  
• 
be given an explanation of the procedures to be followed in the medical 
experiment, and any drug or device to be utilized;  
• 
be given a description of any attendant discomforts and risks reasonably to be 
expected;  
• 
be given an explanation of any benefits to the subject reasonably to be expected, 
if applicable;  
• 
be given a disclosure of any appropriate alternatives, drugs or devices that might 
be advantageous to the subject, their relative risks and benefits; 
• 
be informed of the avenues of medical treatment, if any available to the subject 
after the experiment if complications should arise;  
• 
be given an opportunity to ask questions concerning the experiment or the 
procedures involved;  
• 
be instructed that consent to participate in the medical experiment may be 
withdrawn at any time and the subject may discontinue participation without 
prejudice;  
• 
be given a copy of the signed and dated consent form; and  
• 
be given the opportunity to decide to consent or not to consent to a medical 
experiment without the intervention of any element of force, fraud, deceit, duress, 
coercion or undue influence on the subject's decision. 
 
 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 18 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
May we contact you about future studies that may be of interest to you?  YES    NO 
 
Signing your name means you agree to be in this study and that you will receive a 
copy of this signed and dated consent form.  
 
 
_____________________________________  
 
____________ 
Signature of Adult Participant 
 
 
 
 
Date 
 
 
_____________________________________ 
Print Name of Adult Participant 
 
 
_____________________________________                ____________         
If needed: Signature of Legally Authorized 
 
  Date  
Representative (LAR) (e.g., parent, guardian or conservator)    
 
 
_____________________________________             
Print Name of LAR                                         
                      
          
___________________________________ 
LAR’s Authority to Act for Participant  
 
 
(e.g., parent, guardian or conservator) 
 
 
_____________________________________  
 
____________ 
Signature of Person Obtaining Consent  
 
 
Date 
 
 
_____________________________________ 
Print Name of Person Obtaining Consent 
 
The following witness line is to be signed only if the consent is provided as a summary 
form and accompanied by a short form foreign language consent. 
 
 
_____________________________________                     ____________ 
Signature of Witness                                                              Date 
 
 


 
 
IRB Use Only 
Approval Date:    January 18, 2022 
Expiration Date:  January 18, 2023 
STANFORD UNIVERSITY  Research Consent Forms 
Protocol Director:  Andrei Iagaru, MD 
 
 
Protocol Title:  Evaluation of Patients with Low-Risk and Intermediate-Risk Prostate Cancer Scheduled for High-
Dose Rate Brachytherapy Using 68Ga-RM2 PET, 68Ga-PSMA-11 PET and Multi Parametric MRI 
 
Page 19 of 19 
 
IRB-46258_ICF_12July2019 
Participant ID: 
 
 
__________________________________             
 
Print Name of Witness                                         
 
(e.g., staff, translator/interpreter, family member) 
• Translated short form must be signed and dated by both the participant (or their LAR) AND the 
witness. 
• The English consent form (referred to as the "Summary Form" in the regulations): 
− Must be signed by the witness AND the Person Obtaining Consent (POC). 
− The non-English speaking participant/LAR does not sign the English consent. 
− The non-English speaking participant/LAR should not sign the HIPAA participant line 
− If the participant or the LAR is non-English speaking, the Person Obtaining Consent (POC) must 
ensure that 1) the LAR's Description of Authority is completed and 2) that any questions or options 
presented by the consent form are documented and initialed by the POC on the Summary Form, per 
the participant's wishes, as they are understood during the consent process.