Clinical trial NCT03007719
Conditions: Bladder Cancer
Sponsor: Lawrence Fong
Start date: 2017-03-07; Completion date: 2019-01-11
Enrollment: 4 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase II trial studies how well fluorine F 18 Ara-G positron emission tomography (PET)/magnetic resonance (MR) imaging works in measuring clinical response to atezolizumab or patients with cancer receiving standard of care Anti-PD-1/L1. Diagnostic procedures, such as fluorine F 18 Ara-G PET/MR imaging, may help measure a patient's response to standard of care atezolizumab or Anti-PD-1/L1 treatment.

Detailed description:
PRIMARY OBJECTIVES:

I. To assess the change in fluorine F 18 Ara-G (\[18F\]F-AraG) uptake in primary and/or metastatic tumor(s) on whole-body \[18F\]F-AraG PET/MR imaging associated with neoadjuvant atezolizumab and standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment.

SECONDARY OBJECTIVES:

I. To correlate change in \[18F\]F-AraG uptake within the primary tumor with clinical and pathologic response in patients treated with neoadjuvant atezolizumab. (Cohort 1) II. To assess \[18F\]F-AraG uptake in lymphoid organs before and after anti-PD-1 or anti-PD-L1 treatment. (Cohort 1 and 2)

OUTLINE: Patients are assigned to 1 or 2 cohorts.

COHORT I (NEOADJUVANT COHORT): Patients receive fluorine F 18 Ara-G intravenously (IV) and undergo PET/MR imaging over 1.5-3 hours within 7 days of starting standard of care atezolizumab and within 7 days before surgery.

COHORT II (SOC COHORT): Patients receive fluorine F 18 Ara-G IV and undergo PET/MR imaging over 1.5-3 hours within 7 days of initiating course 1 of anti-PD-1 or anti-PD-L1 therapy and between day 15 of course 1 and day 7 of course 2 of anti-PD-1 or anti-PD-L1 treatment.

After completion of study, patients are followed up at days 2 and 8.

Arms: arm 1: Patients with localized bladder cancer who are eligible for the UCSF phase 2 clinical trial of neoadjuvant atezolizumab before definitive surgery (NCT02451423) (Cohort 1). For the neoadjuvant cohort, study participants will undergo whole body PET/MR imaging with \[18F\]F-AraG within 7 days of initiating atezolizumab and within 7 days before surgery. Approximately 12 patients will be enrolled. arm 2: Patients with any cancer type who are planned to initiate standard of care (SOC) anti-PD-1 or anti-PD-L1 treatment (Cohort 2). For the SOC cohort, study participants will undergo whole body PET/MR imaging with \[18F\]F-AraG within 7 days of initiating Cycle 1 anti-PD-1 or anti-PD-L1, and between Cycle 1 Day 15 (C1D15) and Cycle 2 Day 7 (C2D7) anti-PD-1 or anti-PD-L1. Approximately 19 patients will be enrolled.
Interventions: intervention 1: Fluorine F 18 Ara-G intervention 2: Positron Emission Tomography intervention 3: Magnetic Resonance Imaging
Intervention descriptions: intervention 1: Given IV intervention 2: Undergo PET/MR imaging intervention 3: Undergo PET/MR imaging

Protocol documents:
Prot_SAP_001.pdf: 
Proprietary and Confidential 
The information in this document is considered privileged and confidential, and may not be disclosed to others except 
to the extent necessary to obtain Institutional Review Board approval and informed consent, or as required by 
Federal and State laws.  Persons to whom this information is disclosed should be informed that this information is 
privileged and confidential and that it should not be further disclosed. 
Functional imaging of T-cell activation with [18F]F-AraG in urothelial carcinoma 
patients receiving neoadjuvant therapy or patients with cancer receiving standard of 
care anti-PD-1/L1  
Protocol Number:  CC # 16709 
Study Drug:  2′-deoxy-2′-[18F]fluoro-9-β-Darabinofuranosylguanine ([18F]F-AraG) 
Version Number:  3.0 
Version Date:  02-20-2018 
IND Number: 131349 
Principal Investigator (Sponsor-Investigator) 
Lawrence Fong, MD 
University of California San Francisco 
  
 
 
 
E-mail: Lawrence.Fong@ucsf.edu
Statistician 
 
Revision History 
Version 1.0 
03-20-16
Version 1.1 
06-01-16
Version 1.2 
06-29-16
Version 1.3 
Version 1.4 
07-25-16
08-29-16
Version 1.5 
Version 2.0 
06-27-17
02-13-18
Version 3.0 
02-20-18
NCT# 03007719


 
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Phase II – [18F]F-AraG 
 
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Protocol Signature Page 
Protocol No.: 16709 
Version Date: 02-20-2018 
1. I agree to follow this protocol version as approved by the UCSF Protocol Review Committee 
(PRC), Institutional Review Board (IRB), and Data Safety Monitoring Committee (DSMC).  
2. I will conduct the study in accordance with applicable IRB requirements, Federal regulations, 
and state and local laws to maintain the protection of the rights and welfare of study 
participants.  
3. I certify that I, and the study staff, have received the requisite training to conduct this 
research protocol.  
4. I have read and understand the information in the Investigators’ Brochure (or Manufacturer’s 
Brochure) regarding the risks and potential benefits. I agree to conduct the protocol in 
accordance with Good Clinical Practices (ICH-GCP), the applicable ethical principles, the 
Statement of Investigator (Form FDA 1572), and with local regulatory requirements. In 
accordance with the FDA Modernization Act, I will ensure the registration of the trial on the 
www.clinicaltrials.gov website.  
5. I agree to maintain adequate and accurate records in accordance with IRB policies, Federal, 
state and local laws and regulations. 
UCSF Principal Investigator / Study Chair 
 
 
Printed Name 
 
 
Signature 
 
Date 
 
 
 


 
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Abstract 
Title 
Functional imaging of T-cell activation with [18F]F-AraG in urothelial 
carcinoma patients receiving neoadjuvant or patients with cancer receiving 
standard of care anti-PD-1 or anti-PD-L1 
 
Patient 
population 
1. Patients with localized bladder cancer who are eligible for the UCSF 
phase 2 clinical trial of neoadjuvant anti-PD-1 or anti-PD-L1 before 
definitive surgery (NCT02451423) (Cohort 1), and  
2. Patients with any cancer type who are planned to initiate standard of care 
(SOC) anti-PD-1 or anti-PD-L1 (Cohort 2). 
 
Rationale for 
Study 
[18F]F-AraG is a novel PET imaging agent that has demonstrated selectivity 
for activated T-cells in preclinical models and T-cell leukemia cell lines.  
[18F]F-AraG has the potential to serve as a noninvasive functional biomarker 
in the monitoring of T-cell mediated anti-tumor immune response following 
administration of an immunotherapeutic agent. [18F]F-AraG had been 
administered in six healthy volunteers with no > Grade 1 adverse events, and 
the biodistribution of [18F]F-AraG has been determined in these volunteers on 
which radiation dosimetry estimated have been based.  
In this study, [18F]F-AraG uptake in the tumor before and after treatment with 
the anti-PD-1 or anti-PD-L1 antibody will be measured in localized bladder 
cancer patients receiving neoadjuvant anti-PD-1 or anti-PD-L1 in the context 
a clinical trial, as well as in patients with any cancer type (locally advanced or 
metastatic)  receiving SOC anti-PD-1 or anti-PD-L1.  Clinical response as well 
as T cell infiltration within the tumor of a pre-treatment biopsy or resection 
specimen will be correlated with changes in [18F]F-AraG uptake. In the 
neoadjuvant cohort, pathologic response as well as T cell infiltration within 
the tumor of the surgical specimen will also be correlated with changes in 
[18F]F-AraG uptake. Results from this pilot study will help to guide future 
clinical trials of [18F]F-AraG in the monitoring of anti-tumor immune 
responses. 
 
Primary 
Objective 
To assess the change in [18F]F-AraG uptake in primary and/or metastatic 
tumor(s) on whole-body [18F]F-AraG PET/MR imaging associated with 
neoadjuvant and SOC anti-PD-1 or anti-PD-L1 treatment. 
 


 
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Secondary 
Objectives 
1. To correlate change in [18F]F-AraG uptake within the primary tumor with 
clinical and pathologic response in patients treated with neoadjuvant 
anti-PD-1 or anti-PD-L1 (Cohort 1). 
2. To assess [18F]F-AraG uptake in lymphoid organs before and after anti-
PD-1 or anti-PD-L1 (Cohort 1 and 2). 
 
Exploratory 
Objectives 
1. To correlate change in [18F]F-AraG uptake within the primary tumor with 
quantification of tumor-infiltrating T cells in cystectomy specimen (Cohort 
1).  
2. To correlate change in [18F]F-AraG uptake within the primary tumor  
and/or metastatic tumor(s) with quantification of tumor-infiltrating T cells 
in a pre-treatment biopsy or resection specimen (Cohort 1 and 2). 
Study Design 
This is a single-center cross-sectional imaging study in patients with localized 
bladder cancer undergoing neoadjuvant atezolizumab as part of the 
companion clinical trial CC# 14524 (NCT02451423; Phase 2 study of 
atezolizumab in non-metastatic bladder transitional cell carcinoma), and 
patients with any cancer type (locally advanced or metastatic) receiving 
standard of care (SOC) anti-PD-1 or anti-PD-L1. For the neoadjuvant cohort, 
study participants will undergo whole body PET/MR imaging with [18F]F-AraG 
within 7 days of initiating atezolizumab and within 7 days before surgery. For 
the SOC cohort, study participants will undergo whole body PET/MR imaging 
with [18F]F-AraG within 7 days of initiating Cycle 1 anti-PD-1 or anti-PD-L1, 
and between Cycle 1 Day 15 (C1D15) and Cycle 2 Day 7 (C2D7) anti-PD-1 
or anti-PD-L1 (see Study Schema). A Simon’s two-stage design will be 
utilized. 
Number of 
patients 
A total of 31 patients will be enrolled over an accrual period of approximately 
20 months. 12 patients will be enrolled in the neoadjuvant atezolizumab 
cohort, and approximately 19 patients will be enrolled in the SOC anti-PD-1 
or anti-PD-L1 cohort.  
Duration of 
Therapy 
Each patient will undergo two PET/MR imaging scans. The first imaging will 
be performed within 7 days of starting anti-PD-1 or anti-PD-L1 (baseline). The 
second imaging will be performed within 7 days before surgery in the 
neoadjuvant cohort, and between C1D15 and C2D7 anti-PD-1 or anti-PD-L1 
in the SOC cohort. A bolus injection of [18F]F-AraG will be administered at 
each imaging time point. Each injection will be followed by up to two whole-
body PET/MR scans. Each probe injection plus PET/MR imaging session is 
estimated to last up to three hours. 
Duration of 
Follow up 
All patients will be followed for 7 days after each [18F]F-AraG PET/MR imaging 
time point for safety assessment.  


 
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Duration of 
study 
The study is anticipated to reach completion 20 months from the time the 
study opens to accrual. 
Study Drugs 
2′-deoxy-2′-[18F]fluoro-9-β-Darabinofuranosylguanine ([18F]F-AraG) is a 
radiopharmaceutical imaging agent that will be produced under CGMP 
(Current Good Manufacturing Practice) regulations under the direction of Dr. 
Jim Slater in the Department  of Radiology and Biomedical Imaging 
Radiopharmaceutical Facility at UCSF. A one-time nominal injection dose of 
<5.7mCi for male subjects and <4.4mCi for female subjects will be 
administered at each imaging time point. A simultaneous whole body MRI will 
be used for attenuation correction and anatomic localization of [18F]F-AraG 
uptake and SUV calculation. 
Safety 
Assessments 
Patients will be evaluated one day and one week via telephone visit after each 
radiopharmaceutical injection for safety follow-up. All adverse events will be 
recorded. Due to the noninvasive and non-therapeutic nature of the study, 
potential risks of the study are anticipated to be low. 
Unique 
Aspects of 
this Study 
To our knowledge, this is the first study to investigate changes in activated T 
cell localization in the setting of immunotherapy for cancer utilizing functional 
PET imaging. 
 
 
 


 
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Study Schema: 
 
 
 
 
Cohort 2: Standard of care (SOC) (N=19) 
Screening
Anti-PD-1 or anti-PD-L1 every 3 weeks until disease 
progression or unacceptable toxicity per SOC
Screening
Atezolizumab 1200mg every 3 weeks x 
1-3 cycles per CC# 14524
Surgery
Cohort 1: Neoadjuvant (N=12) 
Within 7 days of 
C1D1 atezolizumab 
Within 7 days before 
surgery 
Within 7 days of C1D1 
anti-PD-1 or anti-PD-L1 
Between C1D15 and C2D7 
anti-PD-1 or anti-PD-L1 

Age ≥18 

ECOG 0-1 

Eligible for CC# 14524 or eligible to 
receive anti-PD-1 or anti-PD-L1 per 
SOC 

Measurable disease 

No prior immunotherapy or known 
immunodeficiency 
Whole body [
18F]F-AraG PET/MRI imaging 


 
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List of Abbreviations 
AE 
adverse event 
BMP 
basic metabolic panel 
BUN 
blood urea nitrogen 
CBC 
complete blood cell (count) 
CGMP 
Current Good Manufacturing Practice 
CR 
complete response 
CRC 
Clinical Research Coordinator 
CRF 
case report form 
CT 
computerized tomography 
CTCEA 
Common Terminology Criteria for Adverse Events 
CTLA-4 
cytotoxic T-lymphocyte-associated protein 4 
CTMS 
Clinical Trial Management System 
dCK 
deoxycytidine kinase 
dGK 
doexyguanosine kinase 
DSMC 
Data and Safety Monitoring Committee 
DSMP 
Data and Safety Monitoring Plan 
ECOG 
Eastern Cooperative Oncology Group 
FAC 
2-fluoro-d-(arabinofuranosyl)cytosine 
F-AraG 
2′-deoxy-2′-fluoro-9-β-D-arabinofuranosylguanine 
FDA 
Food and Drug Administration 
FDG 
fluorodeoxyglucose 
F/U 
follow-up 
GCP 
Good Clinical Practice 
HDFCCC 
Helen Diller Family Comprehensive Cancer Center 
HIPAA 
Health Insurance Portability and Accountability Act (HIPAA) 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IND 
investigational new drug application 
IRB 
Institutional Review Board 
IHC 
Immunohistochemistry 
IV 
Intravenous 
MR 
magnetic resonance 
MRI 
magnetic resonance imaging 
NCI 
National Cancer Institute 


 
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List of Abbreviations 
PD-1 
programmed cell death protein 1 
PD-L1 
programmed death-ligand 1 
PET 
positron emission tomography 
PK 
Pharmacokinetics 
PR 
partial response 
PRC 
Protocol Review Committee 
RECIST 
Response Evaluation Criteria in Solid Tumors 
SOC 
standard of care 
SUV 
standardized uptake values 
TURBT 
transurethral resection of bladder tumor 
UA 
urinalysis 
WBC 
white blood cell 
 
 


 
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Table of Contents 
Protocol Signature Page ......................................................................................................... 2 
Abstract 
3 
List of Abbreviations ................................................................................................................ 7 
1 
Background and Study Rationale ................................................................................. 11 
2 
Objectives and Endpoints of the Study ......................................................................... 14 
2.1 
Objectives ......................................................................................................... 14 
2.1.1 
Primary Objective ......................................................................................... 14 
2.1.2 
Secondary Objectives ................................................................................... 14 
2.1.3 
Exploratory Objectives ................................................................................. 15 
2.2 
Endpoints .......................................................................................................... 15 
2.2.1 
Primary Endpoint .......................................................................................... 15 
2.2.2 
Secondary Endpoints .................................................................................... 15 
3 
Study Design ................................................................................................................ 15 
3.1 
Characteristics .................................................................................................. 15 
3.2 
Number of Subjects .......................................................................................... 16 
3.3 
Eligibility Criteria ............................................................................................. 16 
3.3.1 
Inclusion Criteria .......................................................................................... 16 
3.3.2 
Exclusion Criteria ......................................................................................... 16 
3.4 
Duration of Follow Up ..................................................................................... 17 
3.5 
Subject Replacement ........................................................................................ 17 
4 
Imaging Agent .............................................................................................................. 18 
5 
Study Procedures and Observations ............................................................................ 19 
5.1 
Study Assessments ........................................................................................... 19 
5.2 
Study Procedures .............................................................................................. 19 
5.3 
Follow Up Procedures ...................................................................................... 20 
5.4 
Prohibited Medications ..................................................................................... 20 
5.5 
Safety ................................................................................................................ 21 
6 
Study Calendar ............................................................................................................ 21 
7 
Reporting and Documentation of Results ..................................................................... 22 
7.1 
Evaluation of efficacy (or Activity) .................................................................. 22 
7.1.1 
Definitions .................................................................................................... 22 
7.2 
Evaluation of Safety ......................................................................................... 22 
7.3 
Definition of Adverse Events ........................................................................... 22 
7.3.1 
Adverse Event ............................................................................................... 22 
7.3.2 
Adverse Reaction .......................................................................................... 22 
7.4 
Recording of an Adverse Event ........................................................................ 23 
7.5 
Follow-up of Adverse Events ........................................................................... 24 
7.6 
Expedited Reporting ......................................................................................... 24 
8 
Statistical Considerations and Image Analysis ............................................................. 25 
8.1 
Image Processing and Analysis ........................................................................ 25 
8.2 
Sample Size Determination .............................................................................. 25 
8.3 
Accrual Estimates ............................................................................................. 26 


 
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8.4 
Interim Analysis and Safety Stopping Rule ..................................................... 26 
8.5 
Analytic Plan .................................................................................................... 26 
9 
Study Management ...................................................................................................... 27 
9.1 
Pre-study Documentation ................................................................................. 27 
9.2 
Institutional Review Board Approval ............................................................... 27 
9.3 
Informed Consent ............................................................................................. 27 
9.4 
Changes in the Protocol .................................................................................... 28 
10 
Protection of Human Subjects ...................................................................................... 28 
10.1 
Protection from Unnecessary Harm ................................................................. 28 
10.2 
Protection of Privacy ........................................................................................ 28 
References 
29 
Appendices 
30 
Appendix 1 
Performance Status Criteria .......................................................................... 30 
Appendix 2 
Data and Safety Monitoring Plan for a Phase 2 or 3 Institutional Study ......... 31 
Appendix 3 
UCSF Policy/Procedure for Required Regulatory Documents for a UCSF 
Investigator-Initiated Oncology Clinical Trials with an Investigator held 
Investigational New Drug (IND) ..................................................................... 33 
Appendix 4 MRI Screening Form ........................................................................................... 35 
  
 
 
 


 
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1 
Background and Study Rationale 
In recent years, advances in immunotherapy have resulted in remarkable and durable clinical 
responses in a subset of patients with advanced cancers. However, even among the tumor types 
that respond – including advanced melanoma and renal cell carcinoma – only 20%-30% of 
patients benefit from treatment, suggesting intrinsic immune resistance or an insufficient immune 
response (Restifo N et al., 2016). Furthermore, because immunotherapeutic agents act by 
inducing cancer-specific immune responses, clinical responses are typically delayed in 
comparison to conventional cytotoxic agents (Wolchok JD et al., 2009). A significant unmet need 
in the field is therefore the development of biomarkers to predict which patients are most likely to 
benefit from immunotherapy. 
Molecular imaging of immune activation by positron emission tomography (PET) is a potential 
noninvasive strategy to monitor immune activation after treatment with immunotherapy. Increased 
activity of nucleoside salvage pathways has been associated with the proliferation of adaptive 
and innate immune cells (Fox CJ et al., 2005, Soler C., 2001). In preclinical models of cancer and 
autoimmunity, the PET probe [18F]–2-fluoro-d-(arabinofuranosyl)cytosine ([18F]-FAC), which 
targets the deoxycytidine salvage pathway, was shown to localize to sites of immune activation 
(Radu CG et al., 2008) and is predominantly accumulated in proliferative CD8+ T cells (Nair-Gill 
E et al., 2010). 
Recently, a radiofluorinated AraG imaging agent, [18F]F-AraG (2′-deoxy-2′-fluoro-9-β-D-
arabinofuranosylguanine; trade name VisAcT) was synthesized (Namavari M et al., 2010) with a 
goal of development for human use. F-AraG is a fluorinated purine derivative with selective T-cell 
toxicity. A water-soluble AraG prodrug, Nelarabine, is FDA approved for the treatment of relapsed 
T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphomas (DeAngelo DJ, 2009). 
[18F]F-AraG preferentially accumulates in murine and human activated T cells than in naive T cells 
(Figure 1). The accumulation of [18F]F-AraG in human activated T cells is also significantly higher 
than other immune cells, including B cells, macrophages, and dendritic cells (unpublished data). 
Furthermore, endogenously induced anti-tumor immune response in a viral induced 
rhabdomyosarcoma (MSV) mouse model was correlated with enhanced [18F]F-AraG uptake 
within the tumors (Figure 2a). Analysis of isolated tumors showed that tracer preferentially 
accumulated in activated CD8+ T cells (Figure 2b). 
[18F]F-AraG is a high affinity substrate for doexyguanosine kinase (dGK) and a low affinity 
substrate for deoxycytidine kinase (dCK). Both dGK and dCK are over-expressed in activated T 
cells. Blocking the expression of either dGK or dCK causes reduction in [18F]F-AraG 
accumulation, while over-expression of either dGK or dCK leads to increased accumulation of 
[18F]F-AraG. 
The first-in-human study of [18F]F-AraG was performed at UCSF in 2015 (Yaghoubi S et al., 2015). 
[18F]F-AraG was administered at a subpharmacologic, tracer microdose consistent with imaging 
practices in six healthy volunteers (3 males and 3 females). The distribution of the tracer was 
evaluated over the first 4 hours after injection. A representative whole body PET/MR image in a 
healthy volunteer is shown in Figure 3. The tracer was well tolerated by all patients and there 
were no > Grade 1 adverse events. The only AE that occurred in more than one volunteer was 
positive WBC esterase in the urinalysis without urinary symptoms. Normal uptake was seen in 
the clearance organs: liver, kidneys and bladder. There appeared to be uptake in the thyroid and 
parotid glands, as well as limited accumulation in the cardiac muscle.  In these first-in human 
studies, no additional drugs were administered to subjects as the biodistribution was determined 


 
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for radiation dose estimates.  However, in the present study, oral fluid intake and a diuretic 
(furosemide) will be administered for subjects to allow rapid clearance of the excreted radiotracer 
from the renal collecting systems and to provide diluted radiotracer within the background of the 
bladder, and to enable clear evaluation of distribution of the radiopharmaceutical in the walls of 
the ureters, bladder, and surrounding structures.   
Given that immunotherapeutic strategies, in particular immune checkpoint antibodies, focus on 
the generation of T-cell-based antitumor immunity, we hypothesize that uptake of [18F]F-AraG 
within the tumor will correlate with T-cell mediated immune response in cancer patients treated 
with immune checkpoint blockade. In May 2016, atezolizumab (Tecentriq), an anti-PD-L1 
developed by Genentech Inc. was granted FDA approval for the treatment of previously treated 
locally advanced or metastatic urothelial carcinoma that had progressed during or following 
platinum-containing chemotherapy or that had progressed within 12 months of neoadjuvant or 
adjuvant treatment with platinum-containing chemotherapy. This approval was based on results 
of a single-arm phase 2 study of atezolizumab in 310 patients with locally advanced or metastatic 
urothelial carcinoma, demonstrating an objective response rate (ORR) of 14.8% overall, and an 
ORR of 26% in patients classified as PD-L1 positive by immunohistochemistry (Rosenberg JE, 
2009). Since then, in April 2017, atezolizumab was also approved in the front-line setting in 
patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-
based chemotherapy (Balar AV et al., 2017).   
Currently, PD-L1 inhibitors are approved for bladder cancer, non-small cell lung cancer, and 
Merkel cell skin cancer (Merkel cell carcinoma), and PD-1 inhibitors are approved for melanoma 
of the skin, non-small cell lung cancer, kidney cancer, bladder cancer, head and neck cancers, 
and Hodgkin lymphoma. FDA-approved anti-PD-1/L1 medications include: 
• 
Pembrolizumab 
• 
Avelumab 
• 
Atezolizumab 
• 
Nivolumab 
• 
Durvalumab 
 
In this study, patients with localized bladder cancer eligible for a companion neoadjuvant trial of 
atezolizumab in non-metastatic bladder transitional cell carcinoma (CC# 14524; NCT02451423), 
as well as patients with any cancer type (locally advanced or metastatic) planned to receive anti-
PD-1 or anti-PD-L1 per SOC will undergo two whole body PET/MR imaging to assess for changes 
in tracer uptake with PD-L1 blockade. The neoadjuvant cohort in this study provides a unique 
opportunity to evaluate the correlation of post-treatment intratumoral immune filtration as well as 
pathologic clinical response with tracer uptake. Results from this study will guide the development 
of future clinical trials investigating the role of [18F]F-AraG in the monitoring of anti-tumor immune 
responses. 
 
 


 
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Figure 1: [18F]F-AraG preferentially accumulates in activated T cells than in naive T cells. 
(A) Uptake of [18F]F-AraG in human and mouse primary T cells post-stimulation. (B) Pan T cells 
were isolated from spleen and lymph nodes of mice. Untreated cells as well as CD3/CD28 
activated T cells (48 hours) were incubated with [18F]F-AraG before subcutaneous implantation 
into the shoulders before PET/CT imaging. 
A.                                                                                                     B. 
      
 
 
Figure 2: Visualization of endogenously induced anti-tumor immune response in a viral 
induced rhabdomyosarcoma (MSV) mouse model with [18F]F-AraG PET. (A) Viral induced 
rhabdomyosarcoma was implanted in the left hindleg, and P815 mastocytoma (control) was 
implanted in the right shoulder. PET/CT was performed on day 14 during the peak anti-tumor 
immune response in the rhabdomyosarcoma model. (B) CD8+, CD4+ and C19+ cells were 
isolated from rhabdomyosarcoma tumor one hour after probe injection for radioactivity assay. 
 
A.                                                 B. 
    
 
 


 
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Figure 3: Whole body [18F]F-AraG PET/MR image in a healthy volunteer. 
 
 
2 
Objectives and Endpoints of the Study 
2.1 
Objectives 
2.1.1 Primary Objective 
To assess the change in [18F]F-AraG uptake in primary and/or metastatic tumor(s) on whole-body 
[18F]F-AraG PET/MR imaging associated with neoadjuvant and SOC anti-PD-1 or anti-PD-L1 
treatment. 
2.1.2 Secondary Objectives 
1. To correlate change in [18F]F-AraG uptake within the primary tumor with clinical and 
pathologic response in patients treated with neoadjuvant atezolizumab (Cohort 1). 
 
2. To assess [18F]F-AraG uptake in lymphoid organs before and after anti-PD-1 or anti-PD-L1 
(Cohort 1 and 2).   
 


 
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2.1.3 Exploratory Objectives 
1. To correlate change in [18F]F-AraG uptake within the primary tumor with quantification of 
tumor-infiltrating T cells in cystectomy specimen (Cohort 1). 
2. To correlate change in [18F]F-AraG uptake within the primary tumor  and/or metastatic 
tumor(s) with quantification of tumor-infiltrating T cells in a pre-treatment biopsy or resection 
specimen (Cohort 1 and 2). 
 
2.2 
Endpoints 
2.2.1 Primary Endpoint 
To describe the change between pre-treatment and post-treatment maximum standardized 
uptake values (SUVmax) in the primary and/or metastatic tumor(s) on whole-body [18F]F-AraG 
PET/MR imaging by study cohort.    
 
2.2.2 Secondary Endpoints 
1. 
To compare change in SUVmax of the primary tumor in patients who achieve pathologic down-
staging (e.g. complete pathologic response) or clinical response (measured by RECIST 
v1.1), and those without pathologic or clinical response at time of surgery in patients receiving 
neoadjuvant atezolizumab (Cohort 1). 
 
2. 
To describe the change between pre-treatment and post-treatment SUVmax in lymphoid 
organs (e.g. lymph nodes) on whole-body [18F]F-AraG PET/MR imaging (Cohort 1 and 2). 
 
 
2.2.3 Exploratory Endpoints 
 
1. 
To correlate change in SUVmax of the primary tumor with the number of tumor-infiltrating 
CD3+ and CD3+CD8+ T cells in the surgical specimen quantified by immunohistochemistry 
(IHC) and image analysis in patients receiving neoadjuvant atezolizumab (Cohort 1). 
2. 
To correlate change in SUVmax of the primary and/or metastatic tumor(s) with the number of 
tumor-infiltrating CD3+ and CD3+CD8+ T cells in the pre-treatment biopsy or resection 
specimen quantified by immunohistochemistry (IHC) and image analysis in patients receiving 
SOC anti-PD-1 or anti-PD-L1 (Cohort 1 and 2). 
 
3 
Study Design 
3.1 
Characteristics 
This is a single-center cross-sectional imaging study in patients with localized bladder cancer 
undergoing neoadjuvant atezolizumab as part of the companion clinical trial CC# 14524 
(NCT02451423; Phase 2 study of atezolizumab in non-metastatic bladder transitional cell 


 
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carcinoma), and patients with any cancer type (locally advanced or metastatic) receiving SOC 
anti-PD-1 or anti-PD-L1. Only anti-PD-1/L1 FDA approved for a given cancer will be used for 
Cohort 2. For the neoadjuvant cohort, study participants will undergo whole body PET/MR 
imaging with [18F]F-AraG within 7 days of initiating atezolizumab and within 7 days before surgery. 
For the SOC cohort, study participants will undergo whole body PET/MR imaging with [18F]F-AraG 
within 7 days of initiating Cycle 1 anti-PD-1 or anti-PD-L1 and between Cycle 1 Day 15 and Cycle 
2 Day 7 anti-PD-1 or anti-PD-L1. 
3.2 
Number of Subjects 
A total of 31 patients will be enrolled over an accrual period of approximately 20 months. Twelve 
(12) patients will be enrolled in the neoadjuvant atezolizumab cohort, and 19 patients will be 
enrolled in the SOC anti-PD-1 or anti-PD-L1cohort. 
3.3 
Eligibility Criteria 
Patients must have baseline evaluations performed prior to the first injection of [18F]F-AraG and 
must meet all inclusion and exclusion criteria. In addition, the patient must be thoroughly informed 
about all aspects of the study, including the study visit schedule and required evaluations and all 
regulatory requirements for informed consent. The written informed consent must be obtained 
from the patient prior to enrollment. The following criteria apply to all patients enrolled onto the 
study unless otherwise specified. 
3.3.1 Inclusion Criteria 
1. Age >18 years 
2. Histologically or cytologically documented cancer to which anti-PD1 or anti-PDL1 are 
approved therapies 
3. Eligible for with plan to undergo neoadjuvant treatment with atezolizumab followed by 
surgery as part CC# 14524, or planned to undergo treatment with anti-PD-1 or anti-PD-L1 
per standard of care  
4. Must have measurable disease by RECIST v1.1 regardless of disease stage (e.g. 
localized, locally advanced, or metastatic) 
5. In female patients, negative pregnancy test with no plans to become pregnant during the 
duration of the study  
6. Able to provide informed consent and follow the study guidelines 
7. Archival tumor tissue from biopsy or resection will be required for all patients. Archival 
tissue should be of good quality based on total and viable tumor contents. Fine-needle 
aspiration, brushing, and cytologic cell pellets are not acceptable. 
 
3.3.2 Exclusion Criteria  
1. History of prior treatment with immune checkpoint antibodies (e.g. anti-PD-1, anti-PD-L1, 
anti-CTLA-4 antibody) or co-stimulatory agonist antibodies (e.g. anti-41BB, anti-OX40) 
 


 
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a. Prior intravesical treatment with BCG is allowed. However, the last dose must be 
at least 6 weeks from time of enrollment and patients must have documented 
progressive disease at least 6 weeks from completion of last BCG. 
 
2. Diagnosis of immunodeficiency including history of Human Immunodeficiency Virus 
(HIV) 
 
3. Receiving systemic steroid therapy or any form of immunosuppressive therapy within 7 
days prior to first injection of [18F]F-AraG.  
a. Topical and inhaled corticosteroids are allowed. 
 
4. Prior allogeneic stem cell or solid organ transplant 
 
5. Known psychiatric or substance abuse disorders that would interfere with cooperation 
with the requirements of the study 
 
6. Biopsy or resection of the primary tumor within 14 days the first injection of [18F]F-AraG 
 
7. Contraindication to MRI imaging, as determined through review of the UCSF MRI 
screening form by study investigator (Appendix 4) 
a. UCSF screening form available online: 
https://radiology.ucsf.edu/sites/radiology.ucsf.edu/files/wysiwyg/research/brainch
ange/MRI%20Screening%20Form-BrainChange.pdf 
 
8. Evidence of active infection within 14 days of study enrollment 
 
9. Female patients who are pregnant or breastfeeding 
  
10. Inability to receive furosemide (Lasix), in the opinion of the treating investigator 
 
11. Patients that plan to receive off-label use of anti-PD1 or anti-PDL1 
 
3.4 
Duration of Follow Up 
Patients will be followed for 7 days after each [18F]F-AraG PET/MR imaging time point for safety 
assessment. Specifically, patients will be evaluated by telephone one day and one week after 
each radiopharmaceutical injection for safety follow-up. All adverse events will be recorded and 
graded according to CTCAE v4.0. 
3.5 
Subject Replacement  
All patients who receive any dose [18F]F-AraG of will be analyzed for safety. Subjects who 
discontinue from study participation prior to completing a second PET/MR scan will be replaced. 
Patients removed from study for unacceptable treatment related adverse event(s) will be 
followed until resolution or stabilization of all treatment related AEs to Grade 0-1. 
 


 
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4 
Imaging Agent 
[18F]F-AraG is a radiopharmaceutical that will be produced under cGMP under the direction of 
Jim Slater, PhD., in the Department of Radiology and Biomedical Imaging Radiopharmaceutical 
Facility. The radiopharmaceutical will be prepared in the same facility in which the injection and 
imaging will take place, the China Basin Imaging Center. In a prior study of 6 healthy volunteers 
imaged with [18F]F-AraG, there were no Grade >1 adverse events related to tracer injection, and 
organ-specific dosimetry was within acceptable range.  
[18F]F-AraG will be administered by a licensed nuclear medicine technologist under the 
supervision of a physician boarded in nuclear medicine on an outpatient basis. It will be 
administered at a single time point intravenously prior to PET imaging, at a subpharmacologic, 
tracer microdose consistent with imaging practices. The one-time nominal injected dose will be 
less than or equal to 5.7 mCi for male patients and less than or equal to 4.4 mCi for female 
patients. A simultaneous whole body MRI (PET/MR) will be used for attenuation correction and 
anatomic localization of [18F]F-AraG uptake and SUV calculation. Each [18F]F-AraG injection will 
be followed by a whole body PET/MR acquisition, immediately followed by a limited PET/MR 
acquisition that includes only the pelvic region. The patient will not need to be repositioned 
between the acquisitions. The limited PET/MR dedicated pelvic region acquisition will not add 
any additional radiation exposure, and will require only 5-10 additional minutes. Each probe 
injection plus PET/MR imaging session (on and off the scanner) is estimated to last 
approximately 60 to 90 minutes. 
Patients will be asked to drink 16 ounces of water approximately 30 minutes prior to furosemide 
(Lasix) administration. 20 mg Lasix will be administered intravenously 10-30 minutes prior to 
injection of radiopharmaceutical. The patient will void 30 to 45 minutes after Lasix 
administration. PET/MR imaging will then be performed from the bottom up so that the 
surrounding tissues is optimally visualized. After completion of the whole body imaging, a repeat 
3-minute tumor image will be acquired at the end of imaging.  
Figure 4: Bladder tumor visualization with [18F]FDG. (A) No Lasix administration. (B) Patient 
with exophytic bladder mass with Lasix administration at time of tracer injection. (C) Patient with 
bladder thickening with Lasix administration at time of tracer injection.  
A.                                            B.                                          C. 
 


 
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5 
Study Procedures and Observations 
A written, signed, informed consent form (ICF) and a Health Insurance Portability and 
Accountability Act (HIPAA) authorization must be obtained before any study-specific 
assessments are initiated. A copy of the signed ICF will be given to the subject and a copy will be 
filed in the medical record. The original will be kept on file with the study records. 
5.1 
Study Assessments 
The Screening procedures and assessments must be completed within 28 days of the day 1 
Visit unless otherwise noted (i.e., baseline staging scans). 
• 
Vital signs 
• 
Height and weight 
• 
Physical examination and medical history 
• 
Performance status 
• 
Baseline staging scans with CT chest, head, and/or neck + CT or MRI of the 
abdomen/pelvis + bone scan within 42 days of study enrollment  
o Patients may receive staging scans and [18F]F-Ara PET/MR imaging on the same 
day if the patient meets eligibility criteria for the study as assessed by Principal 
Investigator prior to the completion of the scan. 
• 
MRI screening form (Appendix 4) 
• 
Tissue collection 
o Archival tumor tissue from biopsy or resection will be collected for all patients. 
• 
Baseline labs performed during screening window of Day -28 to Day +1 
o CBC with differential* 
o BMP* 
o Urinalysis*  
o Pregnancy test for women of childbearing potential* 
*If already performed in the screening window (e.g. during screening for corresponding 
neoadjuvant atezolizumab study protocol), will not need to be repeated. 
5.2 
Study Procedures 
[18F]F-Ara experimental PET radiopharmaceutical (hereafter referred to as 
“radiopharmaceutical”) 
• 
Vital signs and EKG will be recorded before and after completion of imaging. 
• 
Administration of Furosemide (Lasix) 
o Patients who are not eligible to receive Lasix are excluded from this study 
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o Because [18F]F-AraG is renally excreted with uptake in the urine, patients will be 
encouraged to drink 16 ounces of water approximately 30 minutes before 
furosemide (Lasix) administration, and will receive 20 mg of Lasix intravenously 
within 10-30 minutes prior to injection of the radiopharmaceutical.  
o Patients will void 30 to 45 minutes after Lasix administration. PET/MR imaging 
will then be performed from the bottom up so that the surrounding tissue is 
optimally visualized. 
o A Foley catheter may be placed if Lasix diuresis and voiding fails to provide 
adequate image quality. 
• 
[18F]F-AraG PET/MR imaging 
o Patient shall begin imaging between 1 to 180 minutes after the injection of the 
radiopharmaceutical. Coverage for the scan will extend from the top of the 
patient’s head through the toes.  
o Each [18F]F-AraG injection will be followed by a whole body PET/MR acquisition, 
immediately followed by a limited PET/MR acquisition that includes only the 
targeted tumor region. The patient will not need to be repositioned between the 
acquisitions. The limited PET/MR dedicated target region acquisition will not add 
any additional radiation exposure, and will require only 5-10 additional minutes.  
o Simultaneous whole body MRI (PET/MR) will be performed for attenuation 
correction. 
o Each probe injection plus PET/MR imaging session (on and off the scanner) is 
estimated to last approximately 60 to 90 minutes. 
o No formal report of the findings from imaging studies will be created. Each study 
will be reviewed by a board certified nuclear medicine physician and radiologist 
within one week after completion of the study. An expert molecular imaging 
investigator will analyze all data. 
 
Exception: If an acute and new finding is found on MRI, this finding will be 
reported and documented, and the investigator will be notified. 
5.3 
Follow Up Procedures  
Patients will be evaluated one day and one week by telephone after the radiopharmaceutical 
injection for safety follow-up. All adverse events will be recorded. 
• 
Cohort 1 (neoadjuvant cohort):Following completion of neoadjuvant atezolizumab cycles 
per corresponding study protocol, the patient will return for repeat imaging within 7 days 
of undergoing surgery. 
• 
Cohort 2 (SOC cohort): Between Cycle 1 Day 15 and Cycle 2 Day 7 anti-PD-1 or anti-
PD-L1, the patient will return for repeat imaging. 
 
5.4 
Prohibited Medications 
Patients should receive no systemic therapy for their cancer other than anti-PD-1 or anti-PD-L1 
prior to completion of the two planned [18F]F-AraG PET scans. 


 
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5.5 
Safety  
Patients will be evaluated via telephone on the day after and at one week after each 
radiopharmaceutical injection for safety follow-up. All adverse events will be recorded. For 
patients in the neoadjuvant cohort (Cohort 1), the principle investigator and study personnel 
(e.g. clinical research coordinator) of the corresponding neoadjuvant atezolizumab study will 
also be informed of the [18F]F-AraG PET/MR imaging dates for each patient, and will follow up 
with any adverse events related to imaging during subsequent study clinic visits (e.g. Cycle 1 
Day 1 visit after baseline imaging).   
 
Potential risks of the study are anticipated to be low. Should a patient experience a Grade 1 or 
Grade 2 adverse event at the time of baseline scan which subsequently resolves, he/she may 
proceed with undergoing the second (pre-surgery) PET/MR imaging.  
 
In the situation that a patient experiences a Grade 3 or higher adverse event at the time of 
baseline scan, the study should be permanently discontinued for that patient. The study will be 
halted after one serious adverse reaction attributable to [18F]F-AraG is seen or if over 20% of 
patients experience Grade 3 or higher toxicities for re-evaluation of tracer dose (Section 8.4). 
6 
Study Calendar 
 
 
First (baseline) imaging 
Second imaging 
 
Screening 
(Day -28 
to 1) 
Day 1 
(Image) 
Safety Follow Up 
Day 1 
(Image) 
Safety Follow-Up 
Day 2 
(Tele) 
Day 8 
(Tele) 
Day 2 
(Tele) 
Day 8 
(Tele) 
Informed consent 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
Physical exam 
X 
 
 
 
 
 
 
Performance status 
X 
 
 
 
 
 
 
Baseline staging scans1 
X 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
Vitals2 
X 
X 
 
 
X 
 
 
Pregnancy test3 
X 
 
 
 
 
 
 
CBC, BMP and UA4 
X 
 
 
 
 
 
 
MRI screening form5 
X 
 
 
 
 
 
 
Tissue collection6 
X 
 
 
 
 
 
 
Furosemide (Lasix)7 
 
X 
 
 
X 
 
 
[18F]F-AraG PET/MR 
imaging8 
 
X 
 
 
X 
 
 
Electrocardiogram9 
 
X 
 
 
X 
 
 
AE Assessment9 
 
X 
X 
X 
X 
X 
X 
 
1 Patients may receive staging scans and [18F]F-Ara PET/MR imaging on the same day if the patient meets eligibility criteria for the 
study as assessed by Principal Investigator prior to the completion of the scan. 
2 Vitals consist of heart rate, blood pressure, blood oxygen %, temperature, and respiratory rate. On imaging days, vitals are 
collected before and after imaging. 
3 Pregnancy tests are performed for women of childbearing potential.   
4 Screening labs, including CBC with differential, BMP and urinalysis are required if not already performed by the corresponding 
neoadjuvant atezolizumab study protocol or SOC. 
5 The study investigator will review the UCSF MRI screening form to confirm no contraindication to MRI imaging. 
6 Archival tissue from tumor resection or biopsy should be of good quality based on total and viable tumor contents. Fine-needle 
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7 Patients will be encouraged to drink 16 ounces of water approximately 30 minutes before furosemide (Lasix) administration, and 
will receive 20 mg of Lasix intravenously within 10-30 minutes prior to injection of the radiopharmaceutical. Patients will void 30 to 
45 minutes after Lasix administration before PET/MR imaging. 
8 PET/MR imaging will be performed from the bottom up so that the surrounding tissues is optimally visualized. 
9 Electrocardiograms are assessed before and after imaging. Adverse events are assessed by a physician on the research team 
after imaging. 
 
7 
Reporting and Documentation of Results 
7.1 
Evaluation of efficacy (or Activity) 
7.1.1 Definitions 
Evaluable for toxicity 
All patients will be evaluable for toxicity from the time of [18F]F-AraG administration. 
7.2 
Evaluation of Safety 
Analyses will be performed for all patients receiving the radiotracer.  The study will use the CTCAE 
v4.0 for reporting of adverse events. 
7.3 
Definition of Adverse Events 
7.3.1 Adverse Event 
An adverse event (also known as an adverse experience) is defined as any untoward medical 
occurrence associated with the use of a drug in humans, whether or not considered drug related.  
More specifically, an adverse event (can be any unfavorable and unintended sign (e.g., an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, 
without any judgment about causality.  An adverse event can arise from any use of the drug (e.g., 
off-label use, use in combination with another drug) and from any route of administration, 
formulation, or dose, including an overdose.  
7.3.2 Adverse Reaction 
An adverse reaction is defined as any adverse event caused by the use of a drug.  Adverse 
reactions are a subset of all suspected adverse reactions for which there is reason to conclude 
that the drug caused the event. 
7.3.2.1 Suspected  
A suspected adverse reaction is defined as any adverse event for which there is a reasonable 
possibility that the drug caused the adverse event. For the purposes of IND safety reporting, 
“reasonable possibility” indicates that there is evidence to suggest a causal relationship between 
the drug and the adverse event.  A suspected adverse reaction implies a lesser degree of certainty 
about causality than an adverse reaction. 
7.3.2.2 Unexpected 
An adverse event or suspected adverse reaction is considered unexpected if it is not listed in the 
investigator brochure or package insert(s), or is not listed at the specificity or severity that has 
been observed, or, if an investigator brochure is not required or available, is not consistent with 
the risk information described in the general investigational plan or elsewhere in the current 
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“Unexpected,” as used in this definition, also refers to adverse events or suspected adverse 
reactions that are mentioned in the investigator brochure as occurring with a class of drugs or as 
anticipated from the pharmacological properties of the drug, but are not specifically mentioned as 
occurring with the particular drug under investigation. 
Adverse events that would be anticipated to occur as part of the disease process are considered 
unexpected for the purposes of reporting because they would not be listed in the investigator 
brochure.  For example, a certain number of non-acute deaths in a cancer trial would be 
anticipated as an outcome of the underlying disease, but such deaths would generally not be 
listed as a suspected adverse reaction in the investigator brochure. 
7.3.2.3 Serious 
An adverse event or suspected adverse reaction is considered serious if, in the view of either 
the investigator or sponsor, it results in any of the following outcomes:  
• 
Death 
• 
Life-threatening adverse event 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life function 
• 
Congenital anomaly/birth defect 
Important medical events that may not result in death, are life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or subject and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition.  Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
7.3.2.4 Life-threatening 
An adverse event or suspected adverse reaction is considered life-threatening if, in the view of 
either the investigator or sponsor, its occurrence places the patient or subject at immediate risk 
of death. It does not include an adverse event or suspected adverse reaction that, had it occurred 
in a more severe form, might have caused death.  
7.4 
Recording of an Adverse Event 
All grade 3 and above adverse events will be recorded using the NCI CTCAE v4.0.   The 
Investigator will assign attribution of the possible association of the event with use of the 
investigational drug.  


 
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Relationship  
Attribution  
Description  
Unrelated to investigational 
drug/intervention 
Unrelated 
The AE is clearly NOT related to the 
intervention  
Unlikely 
The AE is doubtfully related to the 
intervention  
Related to investigational 
drug/intervention 
Possible 
The AE may be related to the intervention  
Probable 
The AE is likely related to the intervention  
Definite 
The AE is clearly related to the intervention  
 
Signs or symptoms reported as adverse events will be graded and recorded by the Investigator 
according to the CTCAE.  When specific adverse events are not listed in the CTCAE they will be 
graded by the Investigator as none, mild, moderate or severe according to the following grades 
and definitions: 
Grade 0 
No AE (or within normal limits) 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
Grade 2 
Moderate; minimal, local, or noninvasive intervention (e.g., packing, cautery) 
indicated; limiting age-appropriate instrumental activities of daily living (ADL) 
Grade 
3: 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care ADL 
Grade 
4: 
Life-threatening consequences; urgent intervention indicated 
Grade 
5: 
Death related to AE 
7.5 
Follow-up of Adverse Events 
All adverse events will be followed with appropriate medical management until resolved.  Patients 
removed from study for unacceptable adverse events will be followed until resolution or 
stabilization of the adverse event. For selected adverse events for which administration of the 
investigational drug was stopped, a re-challenge of the subject with the investigational drug may 
be conducted if considered both safe and ethical by the Investigator. 
 
7.6 
Expedited Reporting 
Reporting to the Data and Safety Monitoring Committee 
If a death occurs during the treatment phase of the study or within 30 days after the last 
administration of the study drug(s) and it is determined to be related either to the study drug(s) or 
to a study procedure, the Investigator or his/her designee must notify the DSMC Chair (or qualified 
alternate) within 1 business day of knowledge of the event.  The contact may be by phone or e-
mail. 
Reporting to UCSF Institutional Review Board 
The Principal Investigator must report events meeting the UCSF IRB definition of “Unanticipated 
Problem” (UP) within 10 business days of his/her awareness of the event.  


 
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Expedited Reporting to the Food and Drug Administration 
If the study is being conducted under an IND, the Sponsor-Investigator is responsible for 
determining whether or not the suspected adverse reaction meets the criteria for expedited 
reporting in accordance with Federal Regulations (21 CFR §312.32).  
The Investigator must report in an IND safety report any suspected adverse reaction that is both 
serious and unexpected.  The Sponsor-Investigator needs to ensure that the event meets all three 
definitions:  
• 
Suspected adverse reaction (as defined in 7.3.2.1) 
• 
Unexpected (as defined in 7.3.2.2) 
• 
Serious (as defined in 7.3.2.3) 
If the adverse event does not meet all three of the definitions, it should not be submitted as an 
expedited IND safety report. 
The timeline for submitting an IND safety report to FDA is no later than 15 calendar days after 
the Investigator determines that the suspected adverse reaction qualifies for reporting (21 CFR 
312.32(c)(1)).  
Any unexpected fatal or life-threatening suspected adverse reaction will be reported to FDA no 
later than 7 calendar days after the Investigator’s initial receipt of the information (21 CFR 
312.32(c)(2)).  
Any relevant additional information that pertains to a previously submitted IND safety report will 
be submitted to FDA as a Follow-up IND Safety Report without delay, as soon as the information 
is available (21 CFR 312.32(d)(2)). 
 
8 
Statistical Considerations and Image Analysis 
8.1 
Image Processing and Analysis 
Trained nuclear medicine physicians and molecular imaging scientists will evaluate the 
reconstructed PET, PET/MR images using a PET volume computer-assisted reading software 
package. Volumetric regions of interest will be chosen around tumors based on anatomic (MR) 
images and activity within the tumor will be expressed in a standardized uptake value (SUV) 
format where SUV will be defined as [concentration of tracer in tumor]/(injected dose/body 
weight). Tumor SUV at baseline (before anti-PD-1 or anti-PD-L1 treatment) will be compared 
with the post–therapy values to determine the change in SUV associated with the therapy. 
Whole body images will be analyzed to determine differences in tracer distribution relative to 
pre/post therapy and versus the normal subject pool already studied.    
8.2 
Sample Size Determination 
The sample size determination is based on the primary endpoint of the study, the change between 
pre-treatment and post-treatment SUVmax in the primary and/or metastatic tumor(s) and on [18F]F-
AraG PET/MR imaging. The null hypothesis is that post-treatment SUVmax increases by at least 
2-fold compared to baseline SUVmax in 1% patients. The alternative hypothesis is that post-
treatment SUVmax increases by at least 2-fold compared to baseline SUVmax in 20% patients. For 
the SOC cohort (Cohort 2), a Simon’s two-stage design will be used. Eight patients will be accrued 


 
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initially, if no patient is observed to have a post-treatment SUVmax that increases by at least 2-fold 
compared to baseline SUVmax, the study will be halted; otherwise, an additional 11 patients will 
be accrued. The null hypothesis will be rejected if 2 or more of the 19 patients are observed to 
have at least a 2-fold increase in post-treatment SUVmax compared to baseline SUVmax. This 
design yields a type I error rate of 0.05 and power of 80%. For the neoadjuvant cohort (Cohort 1), 
one-stage design will be applied with 12 patients accrued to ensure 80% power at a significance 
level of 0.05. 
8.3 
Accrual Estimates 
The anticipated accrual rate is approximately 1-2 patients per month, leading to an estimated total 
accrual period of 20 months. Twelve (12) patients are anticipated to be enrolled in the neoadjuvant 
atezolizumab cohort, and 19 patients are anticipated to be enrolled in the SOC anti-PD-1 or anti-
PD-L1 cohort. A total of 31 patients will be accrued. 
8.4 
Interim Analysis and Safety Stopping Rule 
Interim analysis will be performed only for the SOC cohort (Cohort 2). After 8 patients are imaged 
at both baseline and post-treatment time points, the acquired PET/MR imaging results will be 
reviewed. If the post-treatment SUVmax increases by at least 2-fold compared to baseline SUVmax 
for at least one patient, the study will continue accrual for a total of 19 patients. If no patient is 
observed to have a post-treatment SUVmax that increases by at least 2-fold compared to baseline 
SUVmax, the study will be halted and the imaging protocol re-evaluated, with particular attention 
to the post-treatment imaging time point. Subsequently, the scan results will be analyzed on a 
continuous basis, and accrual may be halted to adjust imaging parameters on an as needed basis. 
Complete safety data will also be analyzed at the time of interim analysis. Accrual will be halted 
after one serious adverse reaction attributable to [18F]F-AraG is seen. If Grade 3 or higher 
toxicities are observed in more than 20% of all patients accrued which are attributable to [18F]F-
AraG, the study will be stopped and the dose of the of [18F]F-AraG reexamined.  
8.5 
Analytic Plan 
The median and interquartile range of SUVmax within the tumor and lymphoid tissues across all 
patients will be descriptively reported for baseline (before treatment) and post-treatment images, 
separately. The nonparametric paired Wilcoxon Signed-rank test will be used to assess 
differences in SUVmax before and after treatment. The log2 ratio of post-treatment versus baseline 
SUVmax within the tumor and lymphoid tissues will also be calculated.  
 
To correlate change in SUVmax to clinical and/or pathologic response, patients will be divided into 
two groups: those who achieved clinical response and/or pathologic downs-staging, and those 
who did not. The median and interquartile range of change in SUVmax from baseline to pre-surgery 
in the different groups will be descriptively reported. For Cohort 1, clinical response will be 
determined by abdominal imaging performed <30 days after the last dose of atezolizumab prior 
to cystectomy compared to baseline pre-treatment imaging using RECIST v1.1 criteria, as 
specified in the companion treatment protocol (CC# 14524). For Cohort 1, pathologic response 
will be determined by evidence of down-staging (e.g. from muscle invasive to non-muscle 
invasive, or complete pathologic response) at the time of cystectomy.  
 
Immunohistochemistry for immune infiltration will be performed in the Fong lab (Fong L et al. J 


 
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Natl Cancer Inst 2014). Briefly, 5-micron FFPE slides from archival tumor tissue or cystectomy 
tissue will be used for staining. For double stains, slides will first be incubated with antibody to 
CD8 and visualized with horseradish peroxidase using DAB+, followed by incubation with 
antibody to CD3 and visualized with alkaline phosphatase using Permanent Red. Tissues will be 
counterstained with hematoxyclin before analysis. Automatic cell counts for single- and double-
stained cells will be determined using the Axiovision software (Zeiss, Peabody, MA). The 
correlation between change from baseline to post-treatment SUVmax on [18F]F-AraG PET and 
CD3+ and CD3+CD8+ immune infiltration (#/μm2) by IHC will be determined using Spearman’s 
rho statistic, separately. 
9 
Study Management 
9.1 
Pre-study Documentation 
This study will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki as stated in 21 CFR §312.120(c)(4); consistent with GCP and all applicable 
regulatory requirements. 
Before initiating this trial, the Investigator will have written and dated approval from the Institutional 
Review Board for the protocol, written informed consent form, subject recruitment materials, and 
any other written information to be provided to subjects before any protocol related procedures 
are performed on any subjects.   
The clinical investigation will not begin until either FDA has determined that the study under the 
Investigational Drug Application (IND) is allowed to proceed or the Investigator has received a 
letter from FDA stating that the study is exempt from IND requirements.  
The Investigator must comply with the applicable regulations in Title 21 of the Code of Federal 
Regulations (21 CFR §50, §54, and §312), GCP/ICH guidelines, and all applicable regulatory 
requirements.  The IRB must comply with the regulations in 21 CFR §56 and applicable regulatory 
requirements. 
9.2 
Institutional Review Board Approval 
The protocol, the proposed informed consent form, and all forms of participant information related 
to the study (e.g. advertisements used to recruit participants) will be reviewed and approved by 
the UCSF Institutional Review Board.  Prior to obtaining IRB approval, the protocol must be 
approved by the Helen Diller Family Comprehensive Cancer Center Site Committee and by the 
Protocol Review Committee (PRC).  The initial protocol and all protocol amendments must be 
approved by the IRB prior to implementation.   
9.3 
Informed Consent 
All participants must be provided a consent form describing the study with sufficient information 
for each participant to make an informed decision regarding their participation.  Participants must 
sign the IRB-approved informed consent form prior to participation in any study specific 
procedure.  The participant must receive a copy of the signed and dated consent document.  The 
original signed copy of the consent document must be retained in the medical record or research 
file.  


 
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9.4 
Changes in the Protocol 
Once the protocol has been approved by the IRB, any changes to the protocol must be 
documented in the form of an amendment.  The amendment must be signed by the Investigator 
and approved by PRC and the IRB prior to implementation.   
If it becomes necessary to alter the protocol to eliminate an immediate hazard to patients, an 
amendment may be implemented prior to IRB approval.  In this circumstance, however, the 
Investigator must then notify the IRB in writing within five (5) working days after implementation.  
The Study Chair and the UCSF study team will be responsible for updating any participating sites. 
10 
Protection of Human Subjects 
10.1 Protection from Unnecessary Harm  
Each clinical site is responsible for protecting all subjects involved in human experimentation. This 
is accomplished through the IRB mechanism and the process of informed consent. The IRB 
reviews all proposed studies involving human experimentation and ensures that the subject’s 
rights and welfare are protected and that the potential benefits and/or the importance of the 
knowledge to be gained outweigh the risks to the individual. The IRB also reviews the informed 
consent document associated with each study in order to ensure that the consent document 
accurately and clearly communicates the nature of the research to be done and its associated 
risks and benefits.  
10.2 Protection of Privacy 
Patients will be informed of the extent to which their confidential health information generated 
from this study may be used for research purposes. Following this discussion, they will be asked 
to sign the HIPAA form and informed consent documents. The original signed document will 
become part of the patient’s medical records, and each patient will receive a copy of the signed 
document. The use and disclosure of protected health information will be limited to the individuals 
described in the informed consent document. 


 
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References 
Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-
ineligible patients with locally advanced and metastatic urothelial carcinoma: a single arm, 
multicenter, phase 2 trial. Lancet Oncol 2017. 389(10064):67-76. 
DeAngelo DJ. Nelarabine for the treatment of patients with relapsed or refractory T-cell acute 
lymphoblastic leukemia or lymphoblastic lymphoma. Hemato Oncol Clin North Am 2009. 
23(5):1121-35. 
Fox CJ, Hammerman PS, Thompson CB, et al. Fuel feeds function: energy metabolism and the 
T-cell response. Nat Rev Immunol 2005. 5(11):844-852. 
Fong L, Carroll P, Weinberg V, et al. Activated lymphocyte recruitment into the tumor 
microenvironment following preoperative sipuleucel-T for localized prostate cancer. J Natl 
Cancer Inst 2014. 106(11). 
Nair-Gill E, Wiltzius SM, Wei XX, et al. PET probes for distinct metabolic pathways have 
different cell specificities during immune responses in mice. J Clin Invest 2010. 120(6):2005-
2015. 
Namavari M, Chang Y, Kusler B, et al. Synthesis of 2’-Deoxy-2’-[18F]Fluoro-9-β-D-
Arabinofuranosylguanine: a novel agent for imaging T-cell activation with PET. Mol Imaging Bio 
2011. 13(5):8212-818. 
Radu CG, Shu CJ, Nair-Gill E, et al. Molecular imaging of lymphoid organs and immune 
activation by positron emission tomography with a new [18F]-labeled 2'-deoxycytidine analog." 
Nat Med 2008. 14(7):783-788. 
Restifo NP, Smyth MJ, Snyder A. Acquired resistance to immunotherapy and future challenges. 
Nat Rev Cancer 2016. 16(2):121-126. 
Rosenberg JE, Hoffman-Censits J, Powles T, et al. Atezolizumab in patients with locally 
advanced and metastatic urothelial carcinoma who have processed following treatment with 
platinum-based chemotherapy. Lancet 2016;387(10031):1909-1920. 
Soler C, Garcia-Manteiga J, Valdes R, et al. Macrophages require different nucleoside transport 
systems for proliferation and activation. FASEB J 2001. 15(11):1979-1988. 
Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity in 
solid tumors: immune-related response criteria. Clin Cancer Res 2009. 15(23)7412-7420. 
Yaghoubi S, VanBrocklin H, Verdin E, et al. First in human study of [18F]F-AraG, a PET tracer 
for monitoring anti-tumor immune response during cancer immunotherapy. World Molecular 
Imaging Conference, 2015. 
 
 


 
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Appendices 
Appendix 1 Performance Status Criteria 
ECOG Performance Status Scale 
Karnofsky Performance Scale 
Grade 
Descriptions 
Percent 
Description 
0 
Normal activity 
Fully active, able to carry on all 
pre-disease performance 
without restriction 
100 
Normal, no complaints, no evidence 
of disease 
90 
Able to carry on normal activity; 
minor signs or symptoms of disease 
1 
Symptoms, but ambulatory 
Restricted in physically 
strenuous activity, but 
ambulatory and able to carry out 
work of a light or sedentary 
nature (e.g., light housework, 
office work) 
80 
Normal activity with effort; some 
signs or symptoms of disease 
70 
Cares for self, unable to carry on 
normal activity or to do active work 
2 
In bed < 50% of the time 
Ambulatory and capable of all 
self-care, but unable to carry out 
any work activities 
Up and about more than 50% of 
waking hours 
60 
Requires occasional assistance, but 
is able to care for most of his/her 
needs 
50 
Requires considerable assistance 
and frequent medical care 
3 
In bed > 50% of the time 
Capable of only limited self-
care, confined to bed or chair 
more than 50% of waking hours 
40 
Disabled, requires special care and 
assistance 
30 
Severely disabled, hospitalization 
indicated 
Death not imminent 
4 
100% bedridden 
Completely disabled 
Cannot carry on any self-care 
Totally confined to bed or chair 
20 
Very sick, hospitalization indicated 
Death not imminent 
10 
Moribund, fatal processes 
progressing rapidly 
5 
Dead 
0 
Dead 
 


 
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Appendix 2 Data and Safety Monitoring Plan for a Phase 2 or 3 Institutional Study 
The UCSF Helen Diller Family Comprehensive Cancer Center (HDFCCC) Data and Safety 
Monitoring Committee (DSMC) is responsible for monitoring data quality and subject safety for 
all HDFCCC institutional clinical studies.  A summary of DSMC activities for this study include:  
• 
Review of subject data 
• 
Review of suspected adverse reactions considered “serious” 
• 
Monitoring every six months (depending on study accrual) 
• 
Minimum of a yearly regulatory audit 
Monitoring and Reporting Guidelines 
Investigators will conduct continuous review of data and subject safety and discuss each 
subject’s treatment at monthly Site Committee meetings. These discussions are documented in 
the Site Committee meeting minutes. The discussion will include the number of subjects, 
significant toxicities in accordance with the protocol, and observed responses. 
All institutional Phase 2 or 3 studies are designated with a moderate risk assessment. The data 
is monitored twice per year with twenty percent of the subjects monitored (or at least three 
subjects if the calculated value is less than three). 
Adverse Event Review and Monitoring 
All grade(s) 3-5 adverse events, whether or not unexpected, and whether or not considered to 
be associated with the use of the study drug, will be entered into OnCore®, UCSF’s Clinical 
Trial Management System. 
All grade(s) 3-5 adverse events entered into OnCore® will be reviewed on a monthly basis at 
the Site Committee meetings. The Site Committee will review and discuss the selected toxicity, 
the toxicity grade, and the attribution of relationship of the adverse event to the administration of 
the study drug(s). 
In addition, all suspected adverse reactions considered “serious” entered into OnCore®, will be 
reviewed and monitored by the Data and Safety Monitoring Committee on an ongoing basis and 
discussed at DSMC meetings, which take place every six weeks. 
If a death occurs during the treatment phase of the study or within 30 days after the last 
administration of the study drug(s) and it is determined to be related either to the study drug(s) 
or to a study procedure, the Investigator or his/her designee must notify the DSMC Chair within 
1 business day of knowledge of this event. The contact may be by phone or e-mail. 
Increase in Adverse Event Rates 
If an increase in the frequency of Grade 3 or 4 adverse events (above the rate reported in the 
Investigator Brochure or package insert) is noted in the study, a report should be submitted to 
the DSMC at the time the increased rate is identified. The report will indicate if the incidence of 
adverse events observed in the study is above the range stated in the Investigator Brochure or 
package insert. 
If at any time the Investigator stops enrollment or stops the study due to safety issues, the 
DSMC Chair and DSMC Manager must be notified within 1 business day via e-mail. The DSMC 
must receive a formal letter within 10 business days and the IRB must be notified. 
 
 


 
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Data and Safety Monitoring Committee Contacts: 
DSMC Chair:  
 
DSMC Monitors  
Phone:  
Email: 
Address:  
 
 
 
 
 
 
UCSF Helen Diller Family 
Comprehensive Cancer Center 
San Francisco, CA 94143 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*  DSMP approved by NCI 09/February2012 
 


 
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Appendix 3 UCSF Policy/Procedure for Required Regulatory Documents for a 
UCSF Investigator-Initiated Oncology Clinical Trials with an Investigator held 
Investigational New Drug (IND) 
Purpose 
This policy defines the required Regulatory Documents for Single Site and Multicenter 
Investigator Initiated Oncology Clinical Trials at the Helen Diller Family Comprehensive Cancer 
Center (HDFCCC) where the Principal Investigator (PI) holds the IND. 
Background 
The International Conference on Harmonization (ICH) Good Clinical Practices (GCP) Guidelines 
define Essential Regulatory Documents as those documents which individually and collectively 
permit evaluation of the conduct of a trial and the quality of data produced. These documents 
serve to demonstrate compliance with standards of GCP and with all applicable regulatory 
requirements. Filing essential documents in a timely manner can greatly assist in the successful 
management of a clinical trial. 
The Regulatory Documents will consist of electronic files in both iMedRIS and OnCore®, as well 
as paper files in the Regulatory Binders for both the Coordinating Site and the Participating 
Site(s) in the HDFCCC Investigator Initiated Oncology Clinical Trials. 
Procedures 
1.   HDFCCC Essential Regulatory Documents 
Documents Filed in iMedRIS: 
• 
IRB approvals for initial submission of application, all modifications, and continuing 
annual renewals 
• 
Current and prior approved protocol versions with signed protocol signature page(s) 
• 
IRB approval letters and Informed Consent Form(s) (ICF) 
• 
Current and prior versions of the Investigator Brochure (IB). 
• 
Serious Adverse Event Reporting 
• 
Protocol Violations and Single Patient Exception (SPE) Reports to IRB with supporting 
fax documentation 
Documents Filed in OnCore®: 
• 
Package Insert (if the study drug is commercial) or Investigator Brochure 
• 
Protocol Review Committee (PRC) approved protocols, protocol amendments and 
Summary of Changes (SOC) 
• 
Patient handouts 
• 
Screening/enrollment log 
• 
Data and Safety Monitoring Committee (DSMC) monitoring reports 
• 
OnCore® Case Report Form (CRF) completion manual 
 
 


 
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Documents Filed in Regulatory Binder: 
• 
Completed Food and Drug Administration (FDA) 1572 document with Principal 
Investigator’s signature 
• 
For all Principal Investigators and Sub-Investigators listed on the FDA 1572, will need 
Financial Disclosure Forms, CVs, MD Licenses, Drug Enforcement Agency (DEA) 
Licenses, and Staff Training Documents (i.e. Collaborative Institute Training Initiative 
(CITI), etc.) 
• 
Site Initiation Visit (SIV) minutes and correspondence with participating site(s). 
• 
As applicable, approvals for Biosafety Committee, Radiation Committee, and Infusion 
Center 
• 
Serious Adverse Event (SAE) reports to IRB and sponsor. 
• 
MedWatch reporting to FDA and sponsor 
• 
Delegation of Authority Form 
• 
Drug Destruction Standard Operating Procedure (SOP) 
• 
For all laboratories listed on the FDA 1572, will need CLIA certifications, CAP 
certifications, lab licenses, CVs of Lab Directors, and laboratory reference ranges 
 
 


 
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Appendix 4 MRI Screening Form 
Available online: 
https://radiology.ucsf.edu/sites/radiology.ucsf.edu/files/wysiwyg/research/brainchange/MRI%20
Screening%20Form-BrainChange.pdf 
 

ICF_000.pdf: 
CC# 16709 
ICF 03-09-2018 
PAGE 1 OF 14 
LAWRENCE FONG, MD 
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO 
CONSENT TO PARTICIPATE IN A RESEARCH STUDY 
Study Title: CC# 16709 Functional imaging of T-cell activation with [18F]F-AraG in 
urothelial carcinoma patients receiving neoadjuvant therapy or patients with cancer 
receiving standard of care anti-PD-1/L1  
This is a medical imaging research study.  Your study doctor Lawrence Fong, MD or one of his 
associates from the Helen Diller Family Comprehensive Cancer Center, UCSF Department of 
Interventional Radiology, or Genitourinary Medical Oncology will explain this study to you.  
Medical research studies only include people who choose to take part.  Please take your time to 
make your decision about participating.  You may discuss your decision with your family and 
friends and with your health care team.  If you have any questions, you may ask your study 
doctor. 
You are being asked to take part in this imaging study because you are either you are 
participating in a separate UCSF phase 2 clinical trial of neoadjuvant atezolizumab before 
definitive surgery (IRB# 14-15423, NCT02451423) for your localized bladder cancer or you are 
planning to start treatment with an anti-PD-1 or anti-PD-L1 medication for your locally 
advanced or metastatic cancer as part of standard medical care for your cancer. 
Why is this study being done? 
The purpose of this study is to investigate changes in your cancer’s anti-tumor immune response 
(or activation of T-cell) levels before and after receiving an imaging tracer called [18Fluorine]F-
AraG during whole-body Positron Emission Tomography/Magnetic Resonance (PET/MR) 
imaging.  The investigators are studying the ability of the imaging tracer to serve as a biomarker 
(or a predictor) of clinical response for how well patients can benefit from receiving 
immunotherapy, such as anti-PD-1 or anti-PD-L1. 
In this study, your body will be scanned at two defined time points in a PET/MR machine to 
produce 3-D images of both the physiology (functioning) and anatomy of the body.  These 
images are produced using [18F]F-AraG, a radioactive substance (or tracer), injected through the 
vein in the arm. The images will capture how the tracer moves through the body and where it 
accumulates at different time points before it clears from your system.   
[18F]F-AraG is an imaging agent that has not been approved for routine clinical use by the United 
States Food and Drug Administration (FDA) and is therefore, an “investigational” use in this 
study.  
Cellsight Technologies, Inc., the manufacturer of the imaging tracer, [18F]F-AraG,  is providing 
the tracer at no cost to you. The study is also funded by Genentech Inc. and an internal 
departmental fund to support the investigators. 
IRB NUMBER: 16-20040
IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019
NCT# 03007719


 
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LAWRENCE FONG, MD 
How many people will take part in this study? 
 
A total of 31 patients will be enrolled in this study; 12 patients will be enrolled into the 
neoadjuvant atezolizumab cohort or “Cohort 1” and 19 patients will be enrolled in the standard 
of care (SOC) anti-PD-1 or anti-PD-L1 cohort or “Cohort 2.” 
 
What will happen if I take part in this research study? 
You will be placed in Cohort 1 if you are receiving or plan to receive neoadjuvant atezolizumab 
in the UCSF phase 2 clinical trial #14-1523 or Cohort 2 if you plan are receiving or plan to 
receive an anti-PD-1 or anti-PD-L1 medication as part of standard medical care. Only anti-PD-1 
or anti-PD-L1 medications that are FDA approved for a given cancer will be used for 
participants in Cohort 2. 
Cohort 1 patients treated with neoadjuvant atezolizumab as part of the companion Phase 2 trial 
of non-metastatic bladder transitional cell carcinoma (NCT02451423) will undergo whole body 
PET/MR imaging with [18F]F-AraG at two time points: 1) within 7 days of initiating 
atezolizumab and 2) within 7 days before scheduled surgery. After each imaging time point, the 
study doctor will follow-up by telephone one day after the imaging and again, one week after the 
imaging to check on any side effects you may have. 
Cohort 2 patients treated with standard of care anti-PD-1 or anti-PD-L1 will undergo whole body 
PET/MR imaging with [18F]F-AraG at two time points: 1) within 7 days of initiating Cycle 1 of 
anti-PD-1 or anti-PD-L1 and 2) between Day 15 of Cycle 1 and Day 7 of Cycle 2 anti-PD-1 or 
anti-PD-L1. After each imaging time point, the study doctor will follow-up by telephone one day 
after the imaging and again, one week after the imaging to check on any side effects you may 
have. 
At each imaging time point detailed above, an injection of [18F]F-AraG will be given followed 
by up to 2 whole-body PET/MR scans.  
Before you begin the main part of the study... 
You will need to have the following exams, tests or procedures to find out if you can be in the 
main part of the study. These exams, tests or procedures are part of regular cancer care and may 
be done even if you do not join the study. If you have had some of them recently, they may not 
need to be repeated. This will be up to your study doctor. 
 
All procedures must be done within 28 days prior to the start of the first imaging appointment, 
unless otherwise noted. Patients in Cohort 1 do not need to repeat some of these screening tests if 
they have already been completed for eligibility on the companion Phase 2 trial. 
 
Screening 
This visit will take about 5 hours (or up to 8 hours if baseline tumor imaging is done). 
 
 Consent to participate in this study 
IRB NUMBER: 16-20040
IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
 Health and medical history 
 Physical exam  
 Vital Signs: Measure your blood pressure, temperature, pulse, breathing rate, and oxygen 
saturation; including height and weight.  
 Performance status: Ask you how well you can do the regular activities of daily life 
 MRI screening: You will be asked to fill out a MRI screening form. 
 Baseline tumor imaging: CT chest, abdomen, pelvis, head, and/or neck with contrast (or 
MRI scan of the abdomen/pelvis with or without a bone scan) to assess your disease 
activity. These baseline tumor imaging exams can be completed within 42 days prior to 
the start of the first imaging study or on the day of, if the study doctor determines this is 
safe. 
o A CT scan uses special x-ray equipment to make detailed pictures of body tissues 
and organs.  For the CT scan, you may be given a "contrast material" (a special 
dye that makes it easier for doctors to see different tissues in your body).  The 
contrast material may be given orally (via your mouth), intravenously (via a 
needle in your vein), or rectally (via your anus, which is less likely).  Oral contrast 
material is given to you to drink and is used to help outline the stomach and 
intestines.  Intravenous (IV) contrast material is given to you by injecting the 
contrast material into a line which is attached to a needle in your arm, and is used 
to get clearer pictures of your body cavity.  If necessary, rectal contrast fills up the 
loops of your lower bowel so the doctors can see your tumor better. After you 
have been given the contrast material (either by mouth, by vein, or rectum), you 
will lie flat on a table that will move you into the CT scan machine. You will be 
asked to lie still and may be asked to hold your breath for a few seconds.  The CT 
scan is done in the radiology department and takes about half an hour. 
o An MRI scan takes an image of your body to observe the location and size of 
your tumor.  For the MRI scan, you may be given a "contrast material" (a special 
dye that makes it easier for doctors to see different tissues in your body).  
Gadolinium is contrast material that causes some tumors to appear much brighter 
than normal tissue on MRI scans (these tumors may not be visible without 
gadolinium).  The contrast material may be given to you in your arm through an 
intravenous catheter (a tiny tube inserted into a vein).  You will then lie down on 
a narrow bed which will be placed in a tunnel that is 6 feet long by 22 inches wide 
and open at each end.  You will lie there quietly for about one hour, during which 
time you will hear a loud machine-like noise.  The MRI scan is done in the 
radiology department and takes approximately an hour and a half to complete. 
o A bone scan is a test that makes detailed images of your bones and any tumors on 
them.  Before the bone scan a small amount of radioactive substance, technetium 
99m, is injected into your vein.  About 3 hours later you will lie on a table under a 
machine which will make an image of your bones.  The test itself will take about 
1 hour, but the whole process takes up to 4 hours. 
 Collect urine sample to check for safety factors 
 Collect blood samples (about 2 tablespoons) for: 
1. Routine safety tests 
a. Measuring the chemical parts of your blood (called biochemistry) 
IRB NUMBER: 16-20040
IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
b. Counting the number of white and red blood cells and platelets (called 
hematology) 
2. Pregnancy test for women of childbearing potential 
 Tissue collection 
o Collection of leftover, “archival” tissue from a previous tumor biopsy or resection  
(including transurethral resections for patients with bladder cancer), if available. 
o If archival tissue is not available, extra tumor tissue obtained during a biopsy 
procedure done as part of your regular care (if indicated) can be used for this study. 
This means that the needle inserted during the biopsy procedure may be re-inserted to 
collect additional tissue for this study. 1-3 passes with this needle will be made. This 
procedure will be done at the site where we can most easily get a piece of the tumor. 
The tissue biopsy is used to examine the immune response and genetic changes in the 
tumor. This procedure takes about 30 minutes. If a biopsy procedure is not needed for 
your regular care, then we will not collect additional tumor sample for this study.  
 
During the main part of the study... 
If the exams, tests and procedures show that you can be in the main part of the study, and you 
choose to take part, then you will need the following tests and procedures. 
The following assessments will be performed at each imaging time point 1) within 7 days of 
initiating atezolizumab/anti-PD-1 or anti-PD-L1 (for both Cohort 1 and Cohort 2) and 2) within 7 
days before scheduled surgery (if Cohort 1) or between Day 15 of Cycle 1 and Day 7 of Cycle 2 
anti-PD-1 or anti-PD-L1 (if Cohort 2). Each imaging appointment will take approximately 6 
hours. 
 Vital signs recorded before and after imaging 
 Electrocardiogram (ECG) before and after imaging: records the electrical activity of your 
heart. Wires or “leads” will be attached to your chest with an adhesive and you will be 
asked to lie still while the machine prints out an electrical “record” of your heart activity.  
The procedure is done in the Cardiology Department and takes about 15-30 minutes. 
 Furosemide (Lasix) intravenous administration: 
o The imaging tracer, [18F]F-AraG is processed through your kidneys and taken up 
in the urine which decreases the resolution or sharpness of the images.  In order to 
prevent this, you will intravenously receive 20 mg of furosemide (Lasix), a 
diuretic, within 10-30 minutes before receiving the tracer injection, and 
encouraged to drink 16oz of water approximately 30 minutes before Lasix 
administration. 
o You will then be asked to void 30 to 45 minutes after Lasix administration. A 
urinary catheter may be placed if there is difficulty with voiding. 
 [18F]F-AraG PET/MR imaging: 
o You will lie down on a narrow bed, which will then be placed in a tunnel that is 
about 6 feet long and open at each end.  You will receive an injection of [18F]F-
AraG through an intravenous catheter (IV) and will be asked to remain still during 
the PET/MRI scans.  You may have up to 2 whole-body PET MRI scans and after 
IRB NUMBER: 16-20040
IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
the first whole-body scan, a repeat 3 minute tumor image will be done. You will 
have the opportunity to get up after each scan for a short break.   
o The total scan time will take approximately 1hr and 30 minutes, but can last up to 
3 hours. 
When you are finished with the imaging portion of the study... 
There will be a telephone follow-up the day after (day 2) and a week after (day 8) each imaging 
appointment to record any side effects you may experience. These telephone follow-ups will take 
approximately 10-15 minutes each. 
Study location: All study procedures will be done at both the UCSF China Basin Imaging 
Center and at Helen Diller Comprehensive Cancer Center at Mission Bay, Mt. Zion, and 
Parnassus. 
The study calendar on page 15 outlines the study tests and procedures and when (marked with an 
‘X’) they are expected during the course of the study. 
How long will I be in the study? 
Participation in this study will take a total of 16 days. 
Can I stop being in the study? 
Yes. You can decide to stop at any time. Tell the study doctor if you are thinking about stopping 
or decide to stop. He or she will tell you how to stop your participation safely.  
It is important to tell the study doctor if you are thinking about stopping so that your study doctor 
can evaluate any risks from the study procedures. 
The study doctor may stop you from taking part in this study at any time if he/she believes it is in 
your best interest, if you do not follow the study rules, or if the study is stopped. 
What side effects or risks can I expect from being in the study? 
You may have side effects while on the study. Everyone taking part in the study will be watched 
carefully for any side effects. However, doctors don't know all the side effects that may happen.  
Side effects may be mild or very serious. Your health care team may give you medicines to help 
lessen side effects. Many side effects go away soon after you stop taking the study procedures.  
In some cases, side effects can be serious, long lasting, or may never go away.  
You should talk to your study doctor about any side effects you experience while taking part in 
the study. 
 
IRB NUMBER: 16-20040
IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
Side effects from [18F]F-AraG PET/MR imaging 
[18F]F-AraG PET/MR imaging had been performed on six healthy volunteers, and none had 
serious side effects. The only side effect that was seen in more than one volunteer was positive 
white blood cell (WBC) esterase in the urine without urinary symptoms, and was therefore not 
clinically significant.  
Risks related to study procedures: 
 
Blood drawing (venipuncture) risks:  Drawing blood may cause temporary discomfort from 
the needle stick, bruising, infection, and fainting. 
 
Collection of archival (left-over) tumor tissue: There are no risks associated with collecting 
the left-over samples from a scheduled tumor resection or biopsy. The samples will only be 
collected after the tumor tissue has already been removed from your body from a procedure you 
are already scheduled to have. This will not change or impact the risk of the procedure or surgery 
you are going to have or have already had. 
 
Electrocardiogram (EKG/ECG): The ECG involves placing electrodes on the skin.  You may 
experience an allergic reaction to the adhesive used to attach the electrodes to the skin.  These 
symptoms are generally mild and clear up on their own.  Please let your doctor know if you are 
aware of any allergies. 
 
Urinary catheter risk: A urinary catheter is a tube that is placed through your urethra to empty 
your bladder. You may experience temporary discomfort.  Although unlikely, insertion of this 
catheter can lead to trauma, bleeding and an increased risk of infection.  
 
Intravenous catheter: A needle will be used to inject the imaging tracer, [18F]F-AraG, into your 
vein.  Although unlikely, insertion of the needle may cause pain or a stinging, bruising, bleeding, 
a blood clot, and leakage of study tracer or infection. 
 
Radiation risks: This research study involves exposure to radiation from [18F]F-AraG 
PET/MRI.  This radiation exposure is not necessary for your medical care and is for research 
purpose only.  The additional amount of radiation that you will receive as a result of participation 
in this study will be less than the yearly natural background radiation in the US (3mSv).  The use 
of radiation involves minimal risk and is required to obtain the desired research information.  IF 
you are pregnant or breast feeding, you SHOULD NOT participate in this study.  If you have any 
questions regarding the use of radiation or the risks involved, please consult the study doctor 
conducting the study.  
 
CT scan risks:  CT scans involve the risks of radiation (see above).  In addition, if contrast 
material (iodine dye) is used, there is a slight risk of developing an allergic reaction, from mild 
(itching, rash) to severe (difficulty breathing, shock, or rarely, death).  The contrast material may 
also cause kidney problems, especially if you are dehydrated or have poor kidney function.  The 
study doctors will ask you about any allergies or related conditions before the procedure.  If you 
have any of these problems, you may not be allowed to have a CT scan with contrast. 
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IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
 
Having a CT scan may mean some added discomfort for you.  In particular, you may be bothered 
by feelings of claustrophobia when placed inside the CT scanner, or by lying in one position for 
a long time.  If contrast material is used, you may feel discomfort when it is injected by vein.  
You may feel warm and flushed and get a metallic taste in your mouth. Rarely, the contrast 
material may cause nausea, vomiting or a headache.  
 
PET risks: The PET-CT involves exposure to radiation. The radiation exposure comes from a 
tracer which is a radioactive chemical injected into a vein in your arm. The tracer lets the doctor 
see how your cells are functioning. As with all injections, it may feel like a small sting and there 
may be possible bruising at the injection site. For some patients, having to lie still on the 
scanning table for the length of the procedure may cause some discomfort or pain. The 
radioactive solution does not remain in your system for a long period of time. See Radiation 
Risk. 
 
MRI risks: Because the MRI machine acts like a large magnet, it could move iron-containing 
objects in the MRI room during your examination, which in the process could possibly harm 
you.  Precautions have been taken to prevent such an event from happening; loose metal objects, 
like pocket knives or key chains, are not allowed in the MRI room.  If you have a piece of metal 
in your body, such as a fragment in your eye, aneurysm clips, ear implants, spinal nerve 
stimulators, or a pacemaker, you will not be allowed into the MRI room and cannot have an 
MRI. 
 
Having an MRI may mean some added discomfort for you.  In particular, you may be bothered 
by feelings of claustrophobia and by the loud banging noise during the study.  Temporary 
hearing loss has been reported from this loud noise.  This is why you will be asked to wear ear 
plugs.  At times during the test, you may be asked to not swallow for a while, which can be 
uncomfortable. 
 
Because the risks to a fetus from MRI are unknown, pregnant women must not participate in this 
study.  
 
Contrast agent (gadolinium) risks: A few side effects of gadolinium injection such as mild 
headache, nausea, and local pain may occur. Rarely (less than 1% of the time) low blood pressure 
and lightheadedness occurs. This can be treated immediately with intravenous fluids. Very rarely 
(less than on in one thousand), patients are allergic to gadolinium. These effects are most 
commonly hives and itchy eyes, but more severe reactions have been seen which result in shortness 
of breath. 
 
Patients with severe kidney disease sometimes have a bad reaction to gadolinium contrast. The 
condition is called nephrogenic systemic fibrosis (NSF). It can cause skin to tighten or scar and 
can damage internal organs. Sometimes it can be life-threatening. There are no reports of NSF in 
patients with normal kidney function. Before you have a MRI scan requiring an injection of 
gadolinium contrast, you will have a blood test in order to check the function of your kidneys. 
Based on your medical history and the results of the test, a doctor will decide whether it is safe for 
you to undergo the MRI scans. 
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IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
 
Bone scan: The bone scan involves exposure to radiation. The bone scan involves an injection, 
in a vein in your arm, of a radiotracer (radioactive compound that localizes in the bone). As with 
all injections, it may feel like a small sting and there may be possible bruising at the injection 
site. You may become uncomfortable lying still for the duration of the examination. See 
Radiation Risks 
 
Incidental findings: Although the imaging scans and procedures you will have in this study are 
being undertaken for research purposes only, it is possible that doctors may notice something 
that could be important to your health. In the event that your scans reveal any potential health 
concerns, your images may be referred to a qualified UCSF clinician. If it is discovered that you 
have any incidental findings that require follow-up, the study doctor or a member of the UCSF 
clinical staff may contact you. 
 
Reproductive risks: You should not become pregnant or father a baby while on this study 
because the drugs in this study can affect an unborn baby.  Women should not breastfeed a baby 
while on this study.  It is important to understand that you need to use birth control while on this 
study.  Check with your study doctor about what kind of birth control methods to use and how 
long to use them.  Some methods might not be approved for use in this study.  
 
Unknown risks: The experimental treatments may have side effects that no one knows about 
yet.  The researchers will let you know if they learn anything that might make you change your 
mind about participating in the study. 
 
For more information about risks and side effects, ask your study doctor. 
 
Are there benefits to taking part in the study? 
There will be no direct benefit to you from participating in this study. However, this study will 
help doctors learn more about [18F]F-AraG PET imaging. [18F]F-AraG PET imaging performed 
in animals indicated that it is very specific in localizing activated T cells, a type of immune 
system cell in the body. It is hoped that the information from this study will help with expanding 
imaging of antitumor immune responses, which would be very useful in developing treatments 
for a wide variety of cancers and other diseases. 
 
What other choices do I have if I do not take part in this study? 
Your other choice is to not participate in this study. 
How will information about me be kept confidential? 
 
Participation in research involves some loss of privacy.  We will do our best to make sure that 
information about you is kept confidential, but we cannot guarantee total privacy.  Some 
information from your medical records will be collected and used for this study.  If you do not 
have a UCSF medical record, one will be created for you.  Your signed consent form and some 
of your research tests will be added to your UCSF medical record.  Therefore, people involved 
with your future care and insurance may become aware of your participation and of any 
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IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
information added to your medical record as a result of your participation.  Study tests that are 
performed by research labs, and information gathered directly from you by the researchers will 
be part of your research records but will not be added to your medical record.  Your personal 
information may be given out if required by law.  If information from this study is published or 
presented at scientific meetings, your name and other personal information will not be used. 
Organizations that may look at and/or copy your medical records for research, quality assurance, 
and data analysis include: 
 Cellsight Technologies, Inc. 
 Genentech, Inc. 
 The University of California 
 The National Cancer Institute (NCI) and other government agencies, e.g., the Food and 
Drug Administration (FDA), involved in keeping research safe for people. 
What are the costs of taking part in this study? 
Some of the services you will receive are being done only because you are participating in this 
research study. Examples of these ‘research only’ services include: review of side effects, Lasix 
administration, [18F]F-AraG imaging, and EKGs. Those services will be paid for by the study 
and will not be billed to you or your health insurance company.  If you believe you have 
received a bill for a research related procedure contact the study team and the UCSF Medical 
Center office that sent the bill. 
 
In addition, some of the services you will receive during this research study are considered to be 
“routine clinical services” that you would have received even if you were not participating in the 
research study. Examples are physical exams, baseline tumor imaging, and screening lab tests. 
These services will be billed to your health insurance company, and you will be responsible for 
paying any deductibles, co-payments or co-insurance that are a normal part of your health 
insurance plan.  If you do not have health insurance, you will be responsible for those costs. 
Before you agree to be in this study, you may want to contact your healthcare payer/insurer to 
see if your plan will cover the costs required as part of your participation. You may request 
more information about the costs of participating in this study and discuss this with the study 
team.c 
 
If you have any questions, your doctor and the study team will be able to provide you with 
answers. 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute's Web site at http://cancer.gov/clinicaltrials/understanding/insurance-coverage. You can 
print a copy of the "Clinical Trials and Insurance Coverage" information from this Web site. 
 
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and ask them 
to send you a free copy. 
 
Will I be paid for taking part in this study? 
In return for your time, effort and travel expenses, you will be paid up to $400 for taking part in 
this study. We will give you a prepaid debit card worth $200 after each imaging time point. 
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IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
 
What happens if I am injured because I took part in this study? 
It is important that you tell your study doctor, Lawrence Fong, MD, if you feel that you have 
been injured because of taking part in this study. You can tell the study doctor in person or call 
him/her 
. 
Treatment and Compensation for Injury:  If you are injured as a result of being in this 
study, the University of California will provide necessary medical treatment.  The costs 
of the treatment may be billed to you or your insurer just like any other medical costs, or 
covered by the University of California or the study sponsor, depending on a number of 
factors.  The University and the study sponsor do not normally provide any other form of 
compensation for injury.  For further information about this, you may call the office of 
the Committee on Human Research at 415- 476-1814.  
What are my rights if I take part in this study? 
Taking part in this study is your choice. You may choose either to take part or not to take part in 
the study. If you decide to take part in this study, you may leave the study at any time. No matter 
what decision you make, there will be no penalty to you and you will not lose any of your regular 
benefits. Leaving the study will not affect your medical care. You can still get your medical care 
from our institution.  
We will tell you about new information or changes in the study that may affect your health or 
your willingness to continue in the study. 
In the case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form. 
Who can answer my questions about the study? 
You can talk to your study doctor about any questions, concerns, or complaints you have about 
this study.  Contact your study doctor Lawrence Fong, MD 
. 
If you wish to ask questions about the study or your rights as a research participant to someone 
other than the researchers or if you wish to voice any problems or concerns you may have about 
the study, please call the Office of the Institutional Review Board at 415-476-1814.  
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. 
 
************************************************************ 
IRB NUMBER: 16-20040
IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019


 
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Optional Research 
 
Please note: This section of the informed consent form is about additional research studies 
that are being done with people who are taking part in the main study. You may take part 
in these additional studies if you want to. You can still be a part of the main study even if 
you say "no" to taking part in any of these additional studies. 
 
You can say "yes" or "no" to each of the following studies. Please mark your choice for 
each study. 
 
About Using Blood and Tissue for Research 
 
In the past, you may have had a biopsy or surgical procedure performed as part of your regular 
cancer care. If available, your study doctor would like your permission to collect that tissue 
sample to help better understand your body’s immune response to target an attack on your 
cancer, in addition to helping develop new ways to monitor and treat diseases. During your 
participation in this study you may also undergo a tumor biopsy as part of your standard of care 
(if your doctor thinks it is safe) and your study doctor would also like your permission to collect 
leftover tumor tissue from these procedures. We would like to use the tissue to look for immune 
cells and changes in the genes of the cancer. All information forwarded for analysis will be made 
anonymous.  No one will know that the samples belong to you. 
 
We would also like to save (“bank”) any leftover blood collected as part of research studies for 
future immune monitoring analyses.  
 
If you decide to participate, your leftover tissue taken during biopsy procedures done as part of 
your regular care will be collected and any remaining blood sample from your research blood 
draws will be banked indefinitely.   
The research that may be done with your blood and tissue is not designed specifically to help 
you. It might help people who have cancer and other diseases in the future. Results from the 
analysis will be published but your data will not be reported individually.  Reports about research 
done with your blood and tumor tissue will not be given to you or your doctor. These reports will 
not be put in your health record. The research will not have an effect on your care. 
 
 
 
Things to Think About 
 
The choice to let us keep your blood and tissue samples for research is optional and up to you. 
No matter what you decide to do, it will not affect your care. Sometimes blood and tissue 
samples are used for genetic research (about diseases that are passed on in families). Even if your 
samples are used for this kind of research, the results will not be put in your health records.  
 
You will not be paid for allowing your blood and tumor samples to be used in research even 
though the research done with your samples may help to develop new products in the future. You 
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IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
will not receive any payment or financial benefit from any products, tests, or discoveries derived 
from these samples.  
 
Your sample and information may be kept indefinitely.  However, if you decide that you do not 
want your samples and information to be stored, you can notify the study doctor, Lawrence 
Fong, MD at the address below, and let us know that you want your blood and tissue biopsy 
samples destroyed. We will destroy any identifiable samples however, if any research has 
already been done using the portion of your samples, the data will be kept and analyzed as part 
of those research studies. 
Lawrence Fong, MD 
University of California San Francisco 
 
 
 
In the future, people who do research may need to know more about your health. While the study 
doctor may give them reports about your health, it will not give them your name, address, phone 
number, or any other information that will let the researchers know who you are. 
 
Your tissue will be used only for research and will not be sold. The research done with your 
tissue may help to develop new products in the future. 
 
Benefits 
 
The benefits of research using tissue include learning more about what causes cancer and other 
diseases, how to prevent them, and how to treat them. 
 
Risks 
The greatest risk to you is the release of information from your health records. We will do our 
best to make sure that your personal information will be kept private. The chance that this 
information will be given to someone else is very small. 
Making Your Choice 
Please read the sentence below and think about your choice. After reading the sentence, put your 
initials in the "Yes" or "No" box. If you have any questions, please talk to your doctor or nurse, 
or call the UCSF Institutional Review Board at 415-476-1814.  
No matter what you decide to do, it will not affect your care. 
1. My blood and tissue may be banked for use in future research and testing. 
YES  
NO 
 
 
IRB NUMBER: 16-20040
IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
CONSENT 
 
You have been given copies of this consent form and the Experimental Subject's Bill of Rights to 
keep. 
 
You will be asked to sign a separate form authorizing access, use, creation, or disclosure of 
health information about you. 
 
PARTICIPATION IN RESEARCH IS VOLUNTARY. You have the right to decline to 
participate or to withdraw at any point in this study without penalty or loss of benefits to which 
you are otherwise entitled. 
 
If you wish to participate in this study, you should sign below. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
Participant's Signature for Consent 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Participant  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
 
Signature of Person Obtaining Consent  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Printed Name of Person Obtaining Consent  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
Witness Signature (Only required if the participant is  
a non-English speaker) 
 
 
 
 
 
 
 
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IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019


 
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LAWRENCE FONG, MD 
Study Calendar 
 
 
 
First (baseline) imaging 
Second imaging 
Safety Follow Up 
Safety Follow-Up 
 
Screening 
(Day -28 
to 1) 
Day 1 
(Image) 
Day 2 
(Tele) 
Day 8 
(Tele) 
Day 1 
(Image) 
Day 2 
(Tele) 
Day 8 
(Tele) 
Informed consent 
X 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
Physical exam 
X 
 
 
 
 
 
 
Performance status 
X 
 
 
 
 
 
 
Baseline staging scans 
X 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
Vitals 
X 
X 
 
 
X 
 
 
Pregnancy test 
X 
 
 
 
 
 
 
Screening lab tests 
X 
 
 
 
 
 
 
MRI screening form 
X 
 
 
 
 
 
 
Tissue collection 
X 
 
 
 
 
 
 
Furosemide (Lasix) 
X 
X 
 
 
X 
 
 
[18F]F-AraG PET/MR 
imaging 
 
X 
 
 
X 
 
 
Electrocardiogram 
 
X 
 
 
X 
 
 
Record side effects 
 
X 
X 
X 
X 
X 
X 
IRB NUMBER: 16-20040
IRB APPROVAL DATE: 11/13/2018
IRB EXPIRATION DATE: 11/12/2019