Clinical trial NCT03649841
Conditions: Castration-Sensitive Prostate Carcinoma Metastatic Malignant Neoplasm in the Bone Metastatic Prostate Carcinoma Prostate Adenocarcinoma Prostate Small Cell Neuroendocrine Carcinoma Stage IV Prostate Cancer AJCC v8 Stage IVA Prostate Cancer AJCC v8 Stage IVB Prostate Cancer AJCC v8
Keywords: Prostate Cancer
Sponsor: University of Washington
Start date: 2020-06-29; Completion date: 2023-02-01
Enrollment: 10 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This phase II trial studies how well antiandrogen therapy, abiraterone acetate, and prednisone with or without neutron radiation therapy work in treating patients with prostate cancer. Hormone therapy such as antiandrogen therapy may fight prostate cancer by blocking the production and interfering with the action of hormones. Abiraterone acetate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Neutron radiation therapy uses high energy neutrons to kill tumor cells and shrink tumors. It is not yet known whether antiandrogen therapy, abiraterone acetate, and prednisone with or without neutron radiation therapy may work better in treating patients with prostate cancer.

Detailed description:
OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ADT per standard of care. Beginning 2 months after start of ADT, patients also receive abiraterone acetate and prednisone per standard of care for at least 6 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive ADT, abiraterone acetate, and prednisone as in Arm I. Beginning 8-10 weeks after starting ADT and within 1 week of starting abiraterone acetate, patients also undergo 3-5 fractions of neutron radiation therapy for 2 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 weeks for 6 months.

Arms: arm 1: Patients receive ADT per standard of care. Beginning 2 months after start of ADT, patients also receive abiraterone acetate and prednisone per standard of care for at least 6 months in the absence of disease progression or unacceptable toxicity. arm 2: Patients receive ADT, abiraterone acetate, and prednisone as in Arm I. Beginning 8-10 weeks after starting ADT and within 1 week of starting abiraterone acetate, patients also undergo 3-5 fractions of neutron radiation therapy for 2 weeks in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Antiandrogen Therapy intervention 2: Abiraterone Acetate intervention 3: Prednisone intervention 4: Radiation Therapy
Intervention descriptions: intervention 1: Undergo ADT intervention 2: Undergo Abiraterone Acetate Treatment SOC intervention 3: Undergo Prednisone Treatment SOC intervention 4: Undergo neutron radiation therapy

Protocol documents:
Prot_SAP_001.pdf: 
CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
FRED HUTCHINSON CANCER RESEARCH CENTER
UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE
Radiation Enhancement of Local and Systemic Anti-Prostate Cancer Immune
Responses
Principal Investigator:
Co-Investigators:
Jing Zeng, MD
Associate Professor
Department of Radiation Oncology
University of Washington Medical Center
1959 NE Pacific Street, Box 356043
Seattle, Washington 98195-6043
Phone: 206-598-4100
Fax: 206-598-6218
Email: jzeng13@uw.edu
Evan Y. Yu, MD
Professor, Department of Medicine
Division of Oncology
University of Washington School of Medicine
Seattle Cancer Care Alliance
Ramesh Rengan, MD PhD
Medical Director, SCCA Proton Therapy Center
Professor, Department of Radiation Oncology
University of Washington School of Medicine
Associate Member, Fred Hutchinson Cancer Research
Center
Jay Liao, MD
Associate Professor
Department of Radiation Oncology
University of Washington Medical Center
Kent Wallner, MD
Associate Professor
Department of Radiation Oncology
University of Washington Medical Center
Biostatistician:
Qian (Vicky) Wu, PHD
Assistant Member
Clinical Research Division
Public Health Sciences Division
Fred Hutchinson Cancer Research Center
P a g e | 1


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
CC9938 Protocol Version: October 19, 2020
P a g e | 2


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
Title
Short Title
Protocol Number
Phase
Methodology
Study Duration
Study Center(s)
Objectives
Number of Subjects
Diagnosis and Main
Inclusion Criteria
Study Product, Dose,
Route, Regimen
Duration of
administration
Statistical
Methodology
Study Summary
Radiation Enhancement of Local and Systemic Anti-Prostate Cancer Immune
Responses
Neutron radiation immune response in CSPC
CC9938
Pilot
2 Arm Randomized
2 yrs
University of Washington Medical Center
The primary objective of this study is to assess the systemic immune effects of
radiation with high relative biological effectiveness (RBE) in the form of
neutron radiation, in combination with androgen deprivation therapy (ADT) in
patients with newly diagnosed castration sensitive prostate cancer (CSPC).
Patients on ADT will be randomized to either standard of care abiraterone +
prednisone, or same plus radiation to 1-3 sites of metastatic disease and
undergo blood draws at multiple time points. The primary endpoint will
measure percent change in peripheral blood effector T-cells (CCR7-
/CD45RO-)-post-therapy (3 months after start of ADT, which is also 1 month
post-radiation in the radiation arm).
30 evaluable subjects
Patients diagnosed with CSPC, beginning ADT and abiraterone + prednisone
as first line therapy, eligible for neutron radiation therapy to at least one
metastatic site of disease. Site of radiation does not have to be symptomatic.
All treatments are approved standard of care for patients with CSPC, including
ADT, abiraterone, prednisone, and neutron radiation.
ADT and abiraterone will be given per standard clinical care for at least 6
months or until patients develop progression (unless treating oncologist feels
patient is still deriving benefit from therapy), or intolerable toxicity. Neutron
radiation treatments will be given standard of care as well, for a maximum of 5
daily radiation treatments.
In order to detect an estimated 10% increase in peripheral blood effector T-
cells (CCR7-/CD45RO-)in the neutron arm versus the no radiation arm with a
two-sided type I error rate of 5% and 80% power, while assuming a 10%
standard deviation in each patient group, around 15 patients are required per
arm.
P a g e | 3


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
Table of Contents
1. Introduction                                                                                                                                   4
2. Study Objectives                                                                                                                            8
3. Study Design                                                                                                                                 8
3.1. General Design
3.2. Eligibility
4. Study Registration                                                                                                                         12
5. Radiation Therapy                                                                                                                         12
5.1. Dose Specifications
5.2. Localization, simulation and immobilization
5.3. Target Volumes
5.4. Critical Structures
5.5. Treatment Planning
5.6. Radiation Quality Assurance Reviews
5.7. Radiation Toxicity
5.8. Criteria for Removal/Withdrawal from Treatment
6. Drug Therapy                                                                                                                                14
6.1 Duration of Therapy
7. Adverse Event Reporting Requirements                                                                                        14
7.1. Adverse Event Reporting
7.2. Expected Toxicities
8. Data and Safety Monitoring Plan                                                                                                  15
8.1. Early Stopping Rules
8.2. Interim Data Review
9. Data Management/Confidentiality                                                                                                16
10. Statistical Considerations                                                                                                              16
10.1. Study Population
10.2. Primary Objective
10.3. Secondary Objectives
10.4. Exploratory Objectives
11. References                                                                                                                                     19
P a g e | 4


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
1
Introduction
This document is a protocol for a human research study. This study is to be conducted according to US
and international standards of Good Clinical Practice (FDA Title 21 part 312 and International
Conference on Harmonization guidelines), applicable government regulations and Institutional research
policies and procedures.
Prostate cancer has seen limited success with immunotherapy, although there is suggestion of clinical
activity:
Prostate cancer remains the most common cancer in men in the United States and the number three cause
of cancer death1. Most patients initially present with disease that is sensitive to androgen deprivation
therapy (ADT), and for patients who present with metastatic disease, LHRH agonists such as leuprolide
or LHRH antagonists such as degarelix are commonly used as first line treatment.
Recent trials
LATITIDE and STAMPEDE showed that the addition of abiraterone plus prednisone to ADT in
castration sensitive prostate cancer (CSPC) as part of first line therapy can improve survival over ADT
alone.2,3 Response rate to first line ADT is high but many patients eventually develop metastatic
castration resistant prostate cancer (mCRPC) and therapeutic options become more limited. Although
immense strides have been made in systemic therapy options for mCRPC, there has been limited success
with immunotherapy4. Sipuleucel-T remains the only FDA approved immunotherapy for mCRPC5, with
two phase III trials comparing ipilimumab versus placebo unable to improve overall survival6,7. There
was, however, evidence of clinical activity, with superior progression free survival in the ipilimumab arm
in both trials. The trial by Kwon et al., gave standard photon radiation to a bony site prior to ipilimumab,
based on the hypothesis that radiation could stimulate an immune response and enhance the efficacy of
ipilimumab6,8. Multiple trials are ongoing in mCRPC testing new immunotherapy agents, combinations of
immunotherapy agents, as well as immunotherapy plus radiation4.
Radiation therapy could potentially improve survival in metastatic prostate cancer:
Historically, the only role of radiation therapy in metastatic prostate cancer has been for palliation, either
to address existing symptoms (such as pain from a metastasis in the bone), or prevent future symptoms
(such as radiation to the spine to prevent spinal cord compression). However, two trials were published in
2018-2019 that suggest radiation could improve survival in oligometastatic prostate cancer (limited
number of metastatic sites). The STAMPEDE trial randomized men with newly diagnosed metastatic
prostate cancer to standard of care systemic therapy (ADT with or without chemotherapy) plus or minus
radiation to the prostate9. For patients with limited metastatic disease burden, radiation to the prostate
improved overall survival (HR 0·68, 95% CI 0·52–0·90; p=0·007; 3-year survival 73% with control vs
81% with radiotherapy). Another trial called SABR-COMET randomized patients with oligometastatic
cancers (1-5 metastatic lesions) and controlled primary tumors to standard of care systemic therapy,
versus systemic therapy plus aggressive radiation (stereotactic ablative radiation therapy), and found
radiation improved median progression-free survival to 12.0 months from 6.0 months (HR = 0.47, P
= .0012), and median overall survival to 41 months (95% CI = 26 months–not reached) from 28 months
(95% CI = 19–33 months, HR = 0.57, P = .090)10. Prostate cancer was one of cancer types included in the
SABR-COMET trial. Multiple additional randomized trials are ongoing internationally to investigate the
role of radiation in prolonging survival in metastatic prostate cancer.
ADT has been shown to have an effect on the immune response in prostate cancer:
Although the primary anti-tumor effect of ADT on prostate cancer is directly inducing cancer cell
apoptosis, ADT also has an effect on the adaptive immune response.11 Patients on ADT show an increase
in naïve CD4+ T-cells in peripheral blood of almost 50% by 1 month after starting ADT, likely
P a g e | 5


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
attributable to increased thymic output.12 At the same time, CD4+ and CD8+ T-cells show increased
proliferation in response to stimulation, suggesting the T-cells are not only increasing in number but also
responsiveness. This increased proliferation of around 10% was statistically significant in the effector
cell population at 1 month (Figure 1). However, after 2 years of ADT, a decrease was seen in Th1 and
Th17 effector memory subsets in peripheral blood. Therefore, ADT may induce an anti-tumor immune
response early in the treatment course but eventually contribute to an immunosuppressive environment.13
Standard photon radiation combined with immunotherapy augments anti-tumor activity in solid tumors:
Radiation causes release of tumor antigens and
cytokines into the tumor microenvironment,
which leads to an inflammatory response and
infiltration of immune cells including T-cells
(both cytotoxic and regulatory), dendritic cells,
macrophages, and myeloid-derived suppressor
cells (MDSCs)14. Peripheral blood from patients
with metastatic melanoma receiving radiation to
a single site of disease while on ipilimumab show
that radiation induces an increase in percentage
of CD4+ T-cells, ratio of CD8+ T-cells to Tregs,
decrease in MDSCs, and increase in HLA-DR
expression on monocytes8,15. Clinical reports
have been published with radiation to one tumor
causing an abscopal effect that leads to systemic
regression of disease outside the radiation field,
even in patients who have previously progressed
on immunotherapy8,16,17. Multiple ongoing trials
are testing the combination of immune check-
point blockade with radiation therapy in a variety
of disease sites (NCT01952769, NCT02289209,
NCT02298946).
Figure 1. Change in peripheral blood in 12 patients on ADT
showing statistically significant increase in effector T-cells
(CD4+/CCR7-/CD45RO-) after 1 month compared with
pretreatment (P). Cells were stimulated with anti-CD3 and anti-
CD28 antibodies. Adapted from Morse and McNeel. Human
Immunology 71 (2010): 496-504.
Strengths and limitations of standard photon radiation as an immune-adjuvant:
All of the published data on radiation and its ability to augment response to immunotherapy have been
with standard photon radiation, which is sparsely ionizing with a relative biological effectiveness (RBE)
of ~ 1, compared to 1.1 for protons and 3 or more for densely ionizing radiations such carbon ions and
fast neutrons.18-20 While the mainstay of radiation treatment worldwide is still photon therapy, particle
therapy is increasingly prevalent. The main attraction of particle therapy is the ability to improve dose
conformality by depositing most of the radiation in the tumor and less radiation in normal tissues21.
Although protons are more widely available than carbon or other high RBE particles, protons have similar
biologic efficacy as standard photon therapy (proton RBE ~ 1.1), but fast neutrons and carbon ions have
higher RBE of 3 or more.19-21 Higher RBE particles have a unique ability to overcome hypoxia, cell cycle
radiosensitivity, and other effects that enable some tumors to resist standard photon treatments. For
example, p53 mutated cells, which are associated with more aggressive prostate cancers22, are relatively
radioresistant to standard photon therapy but more susceptible to high RBE radiation, meaning it is likely
that high RBE radiation has a greater impact on the tumor microenvironment and immune milieu23.
P a g e | 6


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
Immunologic effects of high-RBE radiation compared with standard photon radiation:
High RBE particle therapy such as neutrons cause qualitative changes in the sub-cellular distribution and
types of DNA damage, and have the potential to shift cells from an apoptotic cell death mode towards the
more inflammatory, and possibly immunogenic, mitotic catastrophe and necrotic cell death modes.24-26
High RBE therapy may cause a more immunogenic tumor microenvironment via release of more tumor
neoantigens27,28. Mouse total body radiation experiments in the 1970s with neutrons versus standard
photons found that the degree of immunosuppression was dependent on the LET of the radiation
(neutrons have high LET), and mortality from total body radiation differs based on LET, for the same
delivered radiation dose29.
Immunologic effects of standard photon therapy on patients receiving radiation for prostate cancer:
There is limited data on the immune response of patients with prostate cancer receiving palliative
radiation with standard photon therapy alone, without immunotherapy. Schaue et al., looked at peripheral
blood lymphocytes from 20 patients with localized prostate cancer receiving standard photon radiation
treatment. CD8+ T-cells able to bind survivin, which is overexpressed in prostate cancer, was detected in
peripheral blood and increased after therapy in some patients30.
Nesslinger et al., also looked at
peripheral blood in 73 patients with localized prostate cancer undergoing standard treatments including
standard photon radiation31, and found that 13.8% of patients developed treatment associated
autoantibodies detected via Western blot probing against LNCaP cell lysates. It is possible to detect
changes in immune response in peripheral blood after localized radiation therapy for prostate cancer.
Rationale for combination of ADT, abiraterone+prednisone, and neutron radiation for enhancing the
systemic immune response to prostate cancer:
Both ADT and radiation have been shown to modulate the systemic anti-tumor response. Although ADT
might contribute to an anti-tumor immunologic reaction earlier in the treatment course, the effects may
become more immunosuppressive over time.11      Radiation can also be immunosuppressive given that
lymphocytes are extremely sensitive to radiation killing, but the right dose of radiation to a limited area at
the right time can act similarly to a “vaccine” to enhance or induce an immune reaction.14 Adding a short
course of high-intensity radiation early in the ADT treatment course may enhance and prolong the anti-
tumor immunologic changes seen with ADT.
Although ADT with LHRH agonists or antagonists alone have been standard of care first-line therapy in
CSPC for years, results from LATITUDE and STAMPEDE show that the addition of abiraterone +
prednisone improves survival over ADT alone even in the first-line setting, and this treatment
combination is increasingly used to treat patients with newly diagnosed metastatic prostate cancer.2,3
Little is currently known regarding the immunologic effects of abiraterone + prednisone and there are
concerns about immunosuppressive effects of the low dose prednisone given with abiraterone. However,
a randomized phase 2 trial of sipuleucel-T with abiraterone + prednisone showed that concurrent
administration of both therapies did not blunt or alter the immune parameters seen with sipuleucel-T.32 In
vitro studies of abiraterone show it sensitizes prostate tumor cells to T-cell mediated lysis via an
androgen-receptor dependent pathway,33 and can act synergistically with immunotherapy in a mouse
model to control prostate tumors.34     Large series of patients treated with checkpoint inhibitor
immunotherapy needing immunosuppressive therapy (prednisone taper) to manage toxicity have shown
that treatment efficacy is not diminished in patients who received immunosuppressive therapy versus
those who did not, suggesting low dose prednisone does not negate the changes and benefits of
immunotherapy.35,36 It is also plausible that the addition of abiraterone to the treatment regimen induces a
more robust immune response, as testosterone levels are lowered approximately 1-2 logs lower than can
be achieved with LHRH therapy alone37. Therefore, we propose this study to look at the ability of neutron
P a g e | 7


typically had a low tumor
burden and higher fold
change in Ki67+ CD8
arbitrary cutoff of 2.2 fold
to a single index lesion and 4 cycles of anti-CTLA4
1+Eomes+CD8 T cells that are Ki67+GzmB+ after
treatment. Each circle represents a patient.
of immunotherapy. Adapted from
Sander FE et al. Oncotarget. 2016.
CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
radiation to enhance the anti-tumor immunologic changes seen with ADT plus abiraterone and prednisone
in first line therapy for advanced castration sensitive prostate cancer.
Rationale for peripheral blood effector T-cells as surrogate endpoint for systemic immune response:
Various studies have reported on correlations between changes in peripheral blood immune cell subsets
and clinical outcomes, with no current consensus on the most important population changes for prognosis
prediction. However, multiple studies have shown that an increase in peripheral effector T-cells is
correlated with improved clinical outcomes. Sander et al. looked at peripheral blood of 84 patients with
acute myeloid leukemia who were in first remission after chemotherapy, starting maintenance
immunotherapy with low dose IL-2 and histamine dihydrochloride38.
When comparing peripheral cell counts before and after the first
treatment cycle (C1D1 versus C1D21) as shown in Figure 2, patients
who did not ultimately develop disease relapse had an increase in
effector T-cells (CCR7-/CD8 T-cells) of approximately 10%, versus no
significant change in peripheral effector T-cell percentage in patients
who did develop disease relapse.
Immune profiling of peripheral blood from patients on checkpoint
inhibitor immunotherapy has not been widely explored. Huang et al.
looked at peripheral blood of 29 patients with metastatic melanoma Figure 2. Change in percent CCR7-
receiving anti-PD-1 antibody pembrolizumab39.
At 3-weeks into CD8 effector T-cells after first cycle
therapy, frequency of Ki67+ CD8 effector T-cells peaked and then
declined, with highest percent of Ki67+ CD8 T-cells around weeks 3-6
after start of pembrolizumab (Ki67+ CD8 T-cells increased from
around 7% at baseline to around 14-19% at weeks 3-6 post-
pembrolizumab). The increase in Ki67 expression was mostly seen in the
PD-1+ versus PD-1 negative CD8 effector T-cells, with Ki67 increasing
from around 9% at baseline to around 23% at 3-weeks (peak response) in
the PD-1+ CD8 T-cells population, and non-statistically significant
increase in Ki67+ cells in the PD-1 negative CD8 T-cell population
(Figure
3).
Clinical
response was correlated
with the fold change of
PD-1+        Ki67+        CD8
effector T-cells after anti-
PD-1 therapy, adjusted for
baseline tumor burden. Figure 3. Change in percent
Patients with longer PFS Ki67+ CD8 T-cells after start of
pembrolizumab therapy (n=29).
Red line=PD-1+ cells, blue
line=PD-1 negative cells.
Adapted from Huang AC et al.
Figure 4. Change in peripheral blood in 10 patients
effector T-cells. Using an Nature 2017 (545):60-65.
with metastatic melanoma receiving photon radiation        change in Ki67+ PD-1+ CD8 T-cells after anti-PD-1
therapy. Percentage of Eomes+PD-1+ CD8 T cells in         therapy at weeks 3-12 compared to baseline, response rate
post-treatment blood vs change in%PD-                              was 40% (8/20) for patients with Ki67 change above the
fold, and 29% (2/7) for patients below the fold. T-cell
Progression-free survival (PFS) is proportional to
receptor repertoire was compared between pretreatment
circle size and quadrant boundaries are average values
tumor infiltrating T-cells and peripheral blood CD8 T-
for patients under the mean PFS. Concordance index
cells. Across 6 patients, at peak Ki67 expression after
of the random forest model is 0.59. Adapted from
Twyman-Saint Victor C et al. Nature 2015 (520):373-
377.
P a g e | 8


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
anti-PD-1 treatment, 14 clones were present among the top 10 clones in both tumor and blood, supporting
the notion that Ki67+ T-cells in the blood are reinvigorated by anti-PD-1 therapy and contain T-cell
clones that are also present in the tumor. This study shows that it is possible to detect immunologic
changes in peripheral blood after treatment with anti-PD-1 therapy, and changes in Ki67+ CD8 effector
T-cells may peak around weeks 3-6 and be related to clinical outcome.
Twyman-Saint Victor et al. reported on 22 patients with metastatic melanoma treated with
hypofractionated photon radiation to a single index lesion, followed by 4 cycles of anti-CTLA4 antibody
ipilimumab15. Radiation was found to increase the diversity of the T-cell receptor repertoire while anti-
CTLA4 therapy inhibited T-regulatory (Treg) cells and increased the CD8/Treg ratio. For 10 patients
with available pre- and post-treatment blood, two had partial responses in unirradiated tumors and
progression-free survival significantly longer than the median. For both of these patients, the percentages
of Ki67+ GzmB+ cells increased in PD-1+ Eomes+ CD8 effector T-cells after treatment (6-12%
increase), while the proportion of PD-1+ Eomes+ T-cells remained at or below the mean (Fig. 4). In
contrast, patients with a high percentage of PD-1+ Eomes+ T-cells post-treatment did not have partial
responses and had a short progression-free survival, regardless of reinvigoration. Peripheral blood was
collected post-radiation treatment and pre-anti-CTLA4 therapy, as well as every 3 weeks with anti-
CTLA4 therapy for 4 cycles.
Taken together, the studies above suggest that it is possible to detect changes in effector T-cell
populations in the peripheral blood in response to therapies that affect the immune system, and increase in
effector T-cells may be correlated with improved clinical outcomes.
2
Study Objectives
Primary Objective:
Compare the percent change in peripheral blood effector T-cells (CCR7-/CD45RO-) between the ADT+
abiraterone arm and the ADT+ abiraterone+ radiation arm, measured at immediately prior to starting
abiraterone, and 1 month after start of abiraterone (which is also about 1 month after radiation treatment
in the radiation arm).
Secondary Objectives:

To evaluate the rate of patients with undetectable PSA (<0.2 ng/mL) at 6-months after start of
abiraterone.

To evaluate the frequency and severity of toxicities as measured by CTCAE 4.0.
Exploratory Objectives:

Changes in peripheral blood immune cell subpopulations measured via multi-parameter flow
cytometry at all specimen collection time points:
o Important T-cell subsets using markers such as:
CD3/CD8/CD4/Foxp3/CD45RA/CD45RO/CCR7/CD28/CD27/CD57/CD25/HLA-
DR/CTLA4/PD-1
o NK cells will be assessed using CD16/CD56/CD69.
o B-cells and dendritic cells will be analyzed using: CD19, CD123, CD11c, CD86, MHC class
I and II, CD70, and CD54.
o MDSC will be assessed using: CD11b, CD 14, CD33.
P a g e | 9


Randomization
CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023

Next generation sequencing of the T-cell receptor-β locus in genomic DNA from sorted CD4+ and
CD8+ T cell subsets from blood samples using the TRB ImmunoSeq kit (Adaptive Biotechnologies).

Tumor biopsies (of an untreated site) in select patients who consent will be assessed for: cell death,
tumor infiltrating lymphocytes, expression of cell surface markers including HLA, PDL1, and
undergo multiparameter flow cytometry as well as TCR sequencing.
3
Study Design
3.1. General Design
This is a pilot study to test whether densely ionizing, high relative biological effectiveness (RBE)
radiation in the form of neutron radiation, can induce a more robust systemic immune response in
combination with ADT plus abiraterone + prednisone, than ADT plus abiraterone + prednisone alone, in
patients with advanced CSPC. The long-term goal is to improve the response rate to systemic therapy
with addition of focal radiation treatment as a “vaccine”. Trial schema is shown below in Figure 5 and
study calendar in Table 1. Patients with CSPC about to receive ADT plus abiraterone + prednisone
therapy as first-line treatment, and eligible to receive radiation treatment to 1-3 sites of disease, will be
enrolled and randomized onto one of 2 arms: 1) ADT plus abiraterone + prednisone alone; or 2) ADT
plus abiraterone + prednisone and neutron radiation.
Patients with
advanced
CSPC, starting
ADT plus
abiraterone +
prednisone as
first-line
therapy, and
eligible for
radiation
2 months
Start ADT
Arm 1: ADT plus abiraterone + prednisone
1 month
3 months
Start abiraterone + prednisone
Arm 2: Radiation + ADT plus abiraterone + prednisone
1 month
3 months
Radiation AND Start abiraterone + prednisone
= Peripheral blood draw
Figure 5. Clinical trial schema.
P a g e | 10


2-Months After
Start of ADT4
CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
Table 1. Study Calendar
Informed
Consent
1-Month After Start 4-Months After Start Every 4-Weeks9 Until
of Abiraterone+          of Abiraterone+       6-Months After Start
Prednisone7
Prednisone8
of Abiraterone
X
Medical History
Physical Exam
ECOG
Performance
Status
Blood Draw1
Radiation
Treatment
Tumor biopsy
(optional)2
PSA
CT C/A/P3
Survival
X
X
X
X
X
X
X
X
X
X5
X
X
X6
X
X
X
X
X
X
X
X
X
X
X
1Blood draw will consist of 9 tubes: 8 yellow top tubes (BD Vacutainer #364606 Acid citrate dextrose
additives ACD Solution A) and 1 red top tube (BD Vacutainer #367820 Clot Activator) to collect and
store the following: 1) 6 tubes of 0.5 ml serum; 2) 2 tubes of 1.0 ml plasma; 3)
4
tubes
of
0.5
ml
PBMC; and 4) 6 tubes of 1 ml PMBC.
2Tumor biopsy of a non-radiated site will be performed for patients who consent.
3CT C/A/P is preferred but MRI or PET/CT also acceptable.
4Patients may be enrolled onto the trial up to 2 months after starting ADT, and ADT starts from the first
dose of LHRH agonists or antagonists. Patients must be enrolled prior to starting radiation treatment since
randomization must occur to determine if patient will receive radiation treatment. All pre-treatment
assessments must be performed within 30 days of protocol enrollment, except CT C/A/P which must be
within 60 days of protocol enrollment.
5First blood draw must take place after at least 7 weeks on ADT and be ≤1week prior to starting radiation
or abiraterone.
6Radiation treatment can happen between 8-10 weeks after starting ADT and must happen within 1-week
of starting abiraterone (could be either before or after).
7Acceptable date range is 3-5 weeks.
8Acceptable date range is 3-5 months.
9Acceptable date range is every 3-6 weeks.
P a g e | 11


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
Time points for peripheral blood collection are based on prior studies, including Twyman-Saint Victor et
al.15,that show changes in peripheral blood immune cell populations after radiation treatment peak around
2-4 weeks but can persist for months after treatment. Tumor biopsy of a non-radiated site will be
performed for patients who consent, pre-radiation treatment and post-radiation treatment (2-4 weeks after
radiation).
After completion of radiation treatment, patients will continue to obtain PSA checks every 4 weeks per
standard of care until 6 months after start of abiraterone (see study calendar in Table 1), and a research
coordinator will collect survival data until that point. Patient may be followed by local physicians and
does not have to be seen within the UWMC/SCCA system, but will give permission for outside medical
records to be obtained. Patients are considered off-study as defined under section 6.1 Duration of
Therapy.
3.2. Eligibility Criteria
A. Inclusion Criteria

Pathologically proven (either histologic or cytologic) diagnosis of prostate adenocarcinoma with
<50% neuroendocrine differentiation or small cell histology

At least one site of nodal or distant metastatic disease that is measurable by RECIST 1.1 criteria, or a
bony metastasis that is evaluable on both CT and bone scan

No prior orchiectomy.

No androgen deprivation therapy such as treatment with antiandrogens, LHRH agonists or antagonists
for at least one year prior to trial enrollment, and testosterone must be inside normal range prior to
trial enrollment if there is prior history of ADT.

No other systemic anti-cancer therapy, including ADT, for at least 1-year prior to enrollment.

Prior prostate-directed therapies such as prostatectomy or cryotherapy are allowed.

Prior radiation treatments are allowed (prostate or metastatic sites) but must have been completed at
least 3 months prior to starting ADT for this trial.

Patients must have normal organ and marrow function as defined below:
o WBC>3000/mm3
o ANC>1000/mm3
o Platelets > 100,000/mm3
o Creatinine <1.5 institutional ULN or calculated creatinine clearance >30 ml/min
o AST, ALT, and total bilirubin < 3x institutional ULN (unless patient has documented
Gilbert’s syndrome)

No steroids for at least 2 weeks prior to enrollment, and patient must not be expected to require
steroids during the study period, other than the typical low dose steroid that is given with abiraterone
(typically prednisone or prednisolone at 5 mg twice daily).

Zubrod Performance Status 0-2

Age ≥ 18

Patient must sign study specific informed consent prior to study entry

Men who are sexually active must use medically acceptable forms of contraception
B. Exclusion Criteria

Other illnesses with a life expectancy of less than 6 months, including but not limited to unstable
angina, symptomatic congestive heart failure, cardiac arrhythmias.

Psychological or social issues that would prevent patients from informed consent or complying with
study requirements.
P a g e | 12


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023

Subject has a history of unexplained loss of consciousness or transient ischemic attack within 12
months of treatment start.

Individuals on active treatment for a different cancer are excluded. Individuals with a history of other
malignancies are eligible if they are deemed by the investigator to be at low risk for recurrence of that
malignancy.

Known brain metastasis.

Known allergies, hypersensitivity, or intolerance to abiraterone or prednisone.

Prior ADT less than a year, or greater than two months, prior to trial enrollment or prior ADT with
testosterone less than normal.

Must not have a gastrointestinal condition that would interfere with absorption.

There is a potential drug interaction when abiraterone is concomitantly used with a CYP2D6 substrate
narrow therapeutic index (e.g., thioridazine, dextromethorphan), or strong CYP3A4 inhibitors (e.g.,
atazanavir, erythromycin, indinavir, itraconazole, Ketoconazole, nefazodone, nelfinavir, ritonavir,
saquinavir, telithromycin, and voriconazole) or strong inducers (e.g., carbamazepine, Phenobarbital,
phenytoin, rifabutin, rifampin, rifapentine). Caution should be used when patients are on one of these
drugs.

Patients with a history of pituitary or adrenal dysfunction, active or symptomatic viral hepatitis, HIV,
or chronic liver disease are not eligible.

Any chronic medical condition requiring a higher dose of corticosteroid than 10 mg
prednisone/prednisolone once daily
4
Study Registration
Subjects will be registered by the FHCRC/UW Study Coordinator and entered into the OnCore Clinical
Trial Management System (CTMS). A complete, signed, study consent and HIPAA consent are required
for registration.
5
Radiation Therapy
All radiation treatments will be administered at the University of Washington Medical Center. All other
appointments (medical oncology visits, labs, scans, etc.) can occur at either UWMC or SCCA. Protocol
treatment must begin within 30 days of study enrollment.
5.1. Dose Specifications
Radiation treatments will meet all requirements considered standard clinical care. Although the neutron
radiation treatment is the study procedure in this clinical trial, it is routinely given as standard clinical care
in patients with metastatic prostate cancer, either for palliation of existing symptoms (such as pain from a
bone metastasis), or to prevent development of symptoms from a metastatic lesion (such as preventing
future fracture from a bone metastasis), or to potentially improve survival (as seen in the STAMPEDE
and SABR-COMET trials discussed in the Introduction section). The exact role of radiation therapy in
metastatic prostate cancer is controversial (multiple randomized studies are ongoing) and both arms of
this study are acceptable as standard clinical care.
Patients should ideally be treated with 3 fractions of radiation but up to 5 fractions may be allowed if
treating radiation oncologist is concerned with toxicity. All radiation treatments must complete within a 2
week period. Up to 3 sites may be treated concurrently. For neutron radiation, 2.7 Neutron Gy x 3
fractions is the goal dose, but may be decreased to 1.5 Gy x 3-5 fractions at discretion of treating radiation
oncologist.
P a g e | 13


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
5.2. Localization, simulation, and immobilization

All patients will undergo CT based treatment planning at initial simulation per standard clinical care.
Immobilization devices will be used as applicable to treated anatomic region. The CT scan must
capture the region of interest as well as surrounding organs at risk (OAR) with sufficient margin for
treatment planning. The CT scan should be obtained with a uniform slice thickness of less than or
equal to 3 mm throughout. The use of IV contrast is left to the discretion of the treating physician.

All lesions with potential for respiratory motion should be evaluated by appropriate means including
4D CT scan and/or implanted fiducial marker(s). Respiratory motion management including but not
limited to active-breathing control, respiratory gating, and fiducial marker tracking, will be employed
for qualifying patients per standard clinical practice.

Daily image guidance will be employed for target localization.
5.3. Target Volumes
 The gross tumor volume (GTV) is defined as all known gross disease encompassing the selected
index lesion as visualized the planning CT scan and aided by additional diagnostic imaging studies
(PET/CT or MRI). The use of additional diagnostic imaging studies is dependent on the location of
the index lesion and is left to the discretion of the treating physician.
 An internal gross tumor volume (IGTV) is defined for mobile index lesions at the discretion of the
treating physician. A 4-D CT scan will be acquired in order to account for the motion of the lesion
during treatment. The IGTV will be defined as the union of the visualized index lesion on all gated
CT data sets.
 The clinical target volume (CTV) can include a margin of 0-10 mm at the discretion of the treating
physician.
 The planning target volume (PTV) will be defined as per standard of care.
5.4. Critical Structures
Organ at risk volume (OAR) is contoured as visualized on the planning CT or MR scan. Applicable
OARs will be contoured as clinically appropriate based on site treated.
5.5. Treatment Planning

Any clinically acceptable, standard of care planning technique may be employed to deliver radiation
to the index lesion, including 3D conformal treatment, intensity modulated radiation therapy, and
stereotactic radiosurgery. Typically, patients should not be treated with two directly opposed beams
due to the volume of tissue receiving high dose radiation, and using at least 3 beams or 2 non-opposed
beams is encouraged. All plans are subject to review by the PI. All dose calculations will include
corrections for tissue heterogeneities as specified by IROC Houston.

Dose specifications: at least 95% of the target volume (PTV) is covered by at least 90% of the
prescription dose.

Critical Organ Doses: All standard of care critical organ dose-volume limits will be respected.
5.6. Radiation Quality Assurance Reviews
P a g e | 14


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
All patients treated on this protocol will undergo standard review in the Department of Radiation
Oncology. At least two physicians will review the patient history, imaging findings, tumor contours, and
radiation plan.
5.7. Radiation Toxicity
Toxicity will be graded based on CTCAE 4.0.
5.8. Criteria for Removal/Withdrawal from Treatment
Patients will be withdrawn from treatment if their clinical conditions decline so they are no longer able to
tolerate radiation, or are unlikely to clinically benefit from further therapy.
Patients will still receive follow up care per standard of care even if they withdraw from the study. If a
subject withdraws consent to participate in the study or aspects of the study, attempts will be made to
obtain permission to record at least survival data up to 6 months post-treatment.
6
Drug Therapy
Patients will receive ADT and abiraterone + prednisone per standard of care with medical oncology.

ADT will be given as LHRH agonists or antagonists (i.e. leuprolide).

First-generation androgen receptor antagonists such as bicalutamide may be given for up to two
months concurrently when the LHRH agonist is started, but must be discontinued after two
months to minimize potential immunologic impact on subsequent radiation treatment.

Abiraterone acetate will be given per standard clinical care, with prednisone.

Dose adjustments are allowed at the discretion of the treating oncologist after patients have
started on treatment.

No other anti-cancer therapy may be administered during the study.

Bone protective therapy with zoledronic acid or denosumab is allowed.
Abiraterone + prednisone will be administered for at least 6 months, or until disease progression as
defined below, unless treating oncologist feels patient is still deriving a benefit from therapy:

PSA progression per PCWG3 criteria: ≥ 25% and ≥ 2 ng/mL above the nadir, confirmed by a
second value ≥ 3 weeks later

Radiographic progression based on RECIST 1.1 and PCWG3 criteria

Symptomatic progression e.g. worsening pain or investigator discretion
6.1. Duration of Therapy

Disease progression (see above under section 6. Drug Therapy) unless treating oncologist feels
patient is still deriving a benefit from therapy.

Intercurrent illness that prevents further administration of treatment.

Unacceptable adverse event(s).

Subject decides to withdraw from the study.

General or specific changes in the subject's condition render the patient unacceptable for further
treatment in the judgment of the investigator.
7
Adverse Event Reporting Requirements
7.1. Adverse Event (AE) Reporting
P a g e | 15


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
An AE is any undesirable sign, symptom or medical condition or experience that develops or worsens in
severity after starting the first dose of study treatment or any procedure specified in the protocol, even if
the event is not considered to be related to the study. Abnormal laboratory values or diagnostic test results
constitute AEs only if they induce clinical signs or symptoms or require treatment or further diagnostic
tests.
AEs of Grade 3 and above (per CTCAE v4.0) will be monitored and recorded in study-specific case
report forms (CRFs) in the REDCap system from the time of the first study treatment through 30 days
following the end of study treatment, or until the patient receives an alternative anti-cancer therapy,
whichever date comes first. AEs related to tumor biopsies that are done solely for research will be
monitored, recorded, and reported according to the same standards.
7.2. Expected Toxicities
ADT and abiraterone + prednisone will be given per standard of care and is generally well-tolerated based
on
phase
III
data.
Full
prescribing
information
for
abiraterone
can
be
found
at:
https://www.zytiga.com/shared/product/zytiga/zytiga-prescribing-information.pdf.
Prescribing information for prednisone can be found at:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202020s000lbl.pdf,
Prescribing information for leuprolide can be found at: http://www.rxabbvie.com/pdf/lupronuro_pi.pdf.
Neutron radiation will also be given per standard of care at palliative dosing, which is also generally well
tolerated. Exact toxicity depends on site of treatment and typically includes fatigue and dermatitis in the
treatment field.
The grade and severity of the event will be determined using CTCAE v.4.0. The event will be determined
to be expected or unexpected. The determination of whether an AE is expected is based on ADT,
abiraterone, and prednisone-specific adverse event information per prescribing information, as well as site
specific toxicity listed on radiation treatment consent form for patients receiving radiation treatment.
Unexpected AEs are those not listed in the agent-specific adverse event information nor radiation consent
form. The event will be evaluated for relationship to the medical treatment or procedure. The Investigator
should document his/her opinion of the relationship of the event to study medication as follows:
• Unrelated- The adverse event is clearly not related to the investigational agent(s).
• Possible-The adverse event may be related to the investigational agent(s).
• Probable-The adverse event is most likely related to the investigational agent(s).
• Definite- The adverse event is clearly related to the investigational agent(s).
Based on this information, institutional guidelines will be followed regarding whether an adverse event
should be reported as an expedited report in addition to the routinely reported clinical data.
8
Data and Safety Monitoring Plan
Oversight for this study will be provided by the Principal Investigator with delegation of appropriate
responsibilities to sub-investigators and designated study personnel. They will ensure all entry criteria are
met prior to the initiation of the protocol and all study procedures and reporting of adverse events are
performed according to the IRB-approved protocol.
8.1. Early Stopping Rules
P a g e | 16


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
Early stopping of this trial will be any grade 5 adverse events (AEs) or multiple grade 4 (2 or more) AEs
occurring within ≤ 30 days after the end of treatment defined as possibly, probably, or definitely related to
radiation treatment (per CTCAE, v.4.0). All AE’s grade 3 or higher must be reported to the PI within 24
hours.
8.2. Interim Data Review
All immunologic correlate analysis will be batched. Interim reports will be prepared twice per year until
the initial treatment results have been presented or published. In general, the interim reports will contain
the following information:
•
Patient accrual rate with a projected completion date (while the study is still accruing)
•
Total patients accrued
•
Frequencies and severity of adverse events
•
Compliance rates of treatment delivery
Institutional support of trial monitoring will be in accordance with the FHCRC/University of Washington
Cancer Consortium Institutional Data and Safety Monitoring Plan. Under the provisions of this plan,
FHCRC Clinical Research Support (CRS) coordinates data and compliance monitoring conducted by
consultants, contract research organizations, or FHCRC employees unaffiliated with the conduct of the
study. Independent monitoring visits occur at specified intervals determined by the assessed risk level of
the study and the findings of previous visits per the institutional DSMP.
In addition, protocols are reviewed at least annually and as needed by the Consortium Data and Safety
Monitoring
Committee
(DSMC),
FHCRC
Scientific
Review
Committee
(SRC)
and
the
FHCRC/University of Washington Cancer Consortium Institutional Review Board (IRB). The review
committees evaluate accrual, adverse events, stopping rules, and adherence to the applicable data and
safety monitoring plan for studies actively enrolling or treating subjects. The IRB reviews the study
progress and safety information to assess continued acceptability of the risk-benefit ratio for human
subjects. Approval of committees as applicable is necessary to continue the study.
The trial will comply with the standard guidelines set forth by these regulatory committees and other
institutional, state and federal guidelines.
9
Data Management/Confidentiality
The investigator will ensure that data collected conform to all established guidelines. Each subject is
assigned a unique patient number to assure subject confidentiality. Subjects will not be referred to by this
number, by name, or by any other individual identifier in any publication or external presentation. The
licensed medical records department, affiliated with the institution where the subject receives medical
care, maintains all original inpatient and outpatient chart documents.
Subject research files are stored in a secure place (or database). Access is restricted to authorized
personnel.
10
Statistical Considerations
10.1. Study Population
P a g e | 17


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
This is a pilot study comparing the immunologic response to neutron radiation plus ADT and abiraterone
+ prednisone versus ADT and abiraterone + prednisone alone. Patients are expected to receive ADT per
standard clinical care, and study enrollment is allowed up to two months on ADT. After enrollment,
patients are randomized in a 1:1 ratio to two arms to receive either: 1) abiraterone in addition to ADT, or
2) abiraterone+radiation in addition to ADT. There will not be stratification factors. Target accrual is 30
patients receiving treatment per randomization. If a patient enrolls but cannot be randomized or cannot
receive treatment per randomization, they will be off study. Data analysis will be per treatment arm.
10.2. Primary Objective
The primary objective will compare the percent change in peripheral blood effector T-cells (CCR7-
/CD45RO-) between the ADT+abiraterone arm and the ADT+abiraterone+radiation arm, measured at
immediately prior to starting abiraterone, and 1 month after start of abiraterone (which is also about 1
month after radiation treatment in the radiation arm). Percent change in peripheral blood effector T-cells
will be calculated by measuring the difference of the percent peripheral blood effector T-cells for each
patient between two time points: pre-abiraterone treatment and 1 month post-abiraterone treatment (which
is also 1 month post-radiation in the radiation arm). No one has published on the effect of abiraterone on
immune cell populations in the peripheral blood. Depending on distribution of the percent change,
unpaired two-sample t-test, or Wilcoxon rank-sum test, or log transformation will be used to test the null
hypothesis that the percent change in peripheral blood effector T-cells is equal between the two arms.
In order to detect an estimated 10% larger increase in peripheral blood effector T-cells (CCR7-
/CD45RO-) in the radiation arm versus the no radiation arm at 1-month post-abiraterone+radiation, to
achieve 80% power at two-sided type I error of 5%, while assuming a 10% standard deviation in each
patient group, around 15 patients are required per arm. A study by Morse et al. described above in
section 1 saw approximately 10% increase in peripheral blood effector T-cells (CCR7-/CD45RO-) in
response to ADT in patients with prostate cancer at 1-month after starting ADT. Abiraterone further
suppresses testosterone levels in addition to ADT and could cause further changes in peripheral blood
effector T-cells. Multiple other studies referenced above in section 1 show that an approximately 10%
increase in peripheral blood T-cells could be correlated with improved clinical outcomes.
10.3. Secondary Objectives

To evaluate the rate of patients with undetectable PSA (<0.2 ng/mL) at 6-months after start of
abiraterone.
o This rate will be calculated using Kaplan-Meier estimates and reported for all patients on the
trial and for each treatment arm individually. Based on past publications in patients receiving
ADT+abiraterone as first-line therapy, the expected rate of undetectable PSA at 6-months is
around 95%2. This study is not powered to detect a difference between the two arms in this
endpoint, and no comparison is planned for this endpoint between the two arms.

To evaluate the frequency and severity of toxicities as measured by CTCAE 4.0.
o Descriptive statistics will be used to report the frequency and severity of toxicities for all
patients on the trial and for each treatment arm individually.
o Based on past publications in patients receiving ADT+abiraterone as first-line therapy2, 99%
of patients are expected to experience toxicity of any grade, with approximately 50% of
patients experiencing grade 3 or higher toxicity.
o The most common toxicities of any grade include hot flashes (90%), fatigue (77%),
musculoskeletal disorders (72%), impotence (55%), blood count changes (45%), and
cardiovascular disorders (43%).
P a g e | 18


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
o The most common grade 3 or higher toxicities include endocrine disorders (including hot
flashes and impotence) 15%, cardiovascular disorders (10%), musculoskeletal disorders
(7%), and hepatic disorders (7%).
o The radiation treatment is expected to cause toxicity related to palliative radiation, which are
usually mild and transient. Typical toxicities include grade 2 or less fatigue and dermatitis.
Depending on body site treated, nausea, esophagitis, and musculoskeletal pain can also be
seen.
10.4. Exploratory Objectives

Changes in peripheral blood immune cell subpopulations measured via multi-parameter flow
cytometry at all three specimen collection time points will be compared between the arms. Percent of
each immune cell subpopulation in the peripheral blood will be calculated at three time points for
each patient: pre-abiraterone treatment, 1 month post-abiraterone treatment (which is also 1 month
post-radiation in the radiation arm), and 4 months post-abiraterone treatment (also 4 months post-
radiation in the radiation arm). The percent change from pre-treatment to 1-month post-treatment,
and the percent change from pre-treatment to 4-months post-treatment will be calculated for each
patient and compared between the two arms. No one has published on the effect of abiraterone on
immune cell populations in the peripheral blood. Depending on distribution of the percent change,
unpaired two-sample t-test, or Wilcoxon rank-sum test, or log transformation will be used to test the
null hypothesis that the percent change in peripheral blood immune cell subpopulations is equal
between the two arms.
o Important
T-cell
subsets
using
markers
such
as:
CD3/CD8/CD4/Foxp3/CD45RA/CD45RO/CCR7/CD28/CD27/CD57/CD25/HLA-
DR/CTLA4/PD-1
o NK cells will be assessed using CD16/CD56/CD69.
o B-cells and dendritic cells will be analyzed using: CD19, CD123, CD11c, CD86, MHC class
I and II, CD70, and CD54.
o MDSC will be assessed using: CD11b, CD 14, CD33.

Next generation sequencing of the T-cell receptor (TCR)-β locus in genomic DNA from sorted CD4+
and CD8+ T cell subsets from blood samples using the TRB ImmunoSeq kit (Adaptive
Biotechnologies). TCR diversity and clonality for each patient will be compared at the three sample
collection time points: pre-abiraterone treatment, 1 month post-abiraterone treatment (which is also 1
month post-radiation in the radiation arm), and 4 months post-abiraterone treatment (also 4 months
post-radiation in the radiation arm). Hypothesis generating differences will be sought between the
two treatment arms. With 15 patients per arm, we do not expect statistically significant differences
between the two arms.

Tumor biopsies (of an untreated site) in select patients who consent will be assessed for: cell death,
tumor infiltrating lymphocytes, expression of cell surface markers including HLA, PDL1, and
undergo multiparameter flow cytometry as well as TCR sequencing. TCR clonotypes will be
compared in tumor biopsies and peripheral blood.
P a g e | 19


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
References
1.
 Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA: a cancer journal for clinicians. Jan
2017;67(1):7-30.
2.
 James ND, de Bono JS, Spears MR, et al. Abiraterone for Prostate Cancer Not Previously Treated
with Hormone Therapy. The New England journal of medicine. Jul 27 2017;377(4):338-351.
3.
 Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive
Prostate Cancer. The New England journal of medicine. Jul 27 2017;377(4):352-360.
4.
 McNeel DG, Bander NH, Beer TM, et al. The Society for Immunotherapy of Cancer consensus
statement on immunotherapy for the treatment of prostate carcinoma. Journal for immunotherapy
of cancer. 2016;4:92.
5.
 Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant
prostate cancer. The New England journal of medicine. Jul 29 2010;363(5):411-422.
6.
 Kwon ED, Drake CG, Scher HI, et al. Ipilimumab versus placebo after radiotherapy in patients
with metastatic castration-resistant prostate cancer that had progressed after docetaxel
chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial. The Lancet.
Oncology. Jun 2014;15(7):700-712.
7.
 Beer TM, Kwon ED, Drake CG, et al. Randomized, Double-Blind, Phase III Trial of Ipilimumab
Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic
Chemotherapy-Naive Castration-Resistant Prostate Cancer. Journal of clinical oncology : official
journal of the American Society of Clinical Oncology. Jan 2017;35(1):40-47.
8.
 Postow MA, Callahan MK, Barker CA, et al. Immunologic correlates of the abscopal effect in a
patient with melanoma. The New England journal of medicine. Mar 8 2012;366(10):925-931.
9.
 Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumour for newly
diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial.
Lancet. Dec 1 2018;392(10162):2353-2366.
10.
 Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care
palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised,
phase 2, open-label trial. Lancet. May 18 2019;393(10185):2051-2058.
11.
 Kalina JL, Neilson DS, Comber AP, et al. Immune Modulation by Androgen Deprivation and
Radiation Therapy: Implications for Prostate Cancer Immunotherapy. Cancers. Jan 27 2017;9(2).
12.         Morse MD, McNeel DG. Prostate cancer patients on androgen deprivation therapy develop
persistent changes in adaptive immune responses. Human immunology. May 2010;71(5):496-504.
13.
 Tang S, Moore ML, Grayson JM, Dubey P. Increased CD8+ T-cell function following castration
and immunization is countered by parallel expansion of regulatory T cells. Cancer research. Apr
15 2012;72(8):1975-1985.
14.
 Weichselbaum RR, Liang H, Deng L, Fu YX. Radiotherapy and immunotherapy: a beneficial
liaison? Nat Rev Clin Oncol. Jan 17 2017.
15.
 Twyman-Saint Victor C, Rech AJ, Maity A, et al. Radiation and dual checkpoint blockade
activate non-redundant immune mechanisms in cancer. Nature. Apr 16 2015;520(7547):373-377.
16.
 Wada S, Jackson CM, Yoshimura K, et al. Sequencing CTLA-4 blockade with cell-based
immunotherapy for prostate cancer. Journal of translational medicine. Apr 04 2013;11:89.
17.
 Dewan MZ, Galloway AE, Kawashima N, et al. Fractionated but not single-dose radiotherapy
induces an immune-mediated abscopal effect when combined with anti-CTLA-4 antibody.
Clinical cancer research : an official journal of the American Association for Cancer Research.
Sep 1 2009;15(17):5379-5388.
18.
 Paganetti H. Relative biological effectiveness (RBE) values for proton beam therapy. Variations
as a function of biological endpoint, dose, and linear energy transfer. Physics in medicine and
biology. Nov 21 2014;59(22):R419-472.
P a g e | 20


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
19.
 Skarsgard LD. Radiobiology with heavy charged particles: a historical review. Physica medica :
PM : an international journal devoted to the applications of physics to medicine and biology :
official journal of the Italian Association of Biomedical Physics. Jul 1998;14 Suppl 1:1-19.
20.
 Stewart RD, Yu VK, Georgakilas AG, Koumenis C, Park JH, Carlson DJ. Effects of radiation
quality and oxygen on clustered DNA lesions and cell death. Radiation research. Nov
2011;176(5):587-602.
21.
 Loeffler JS, Durante M. Charged particle therapy--optimization, challenges and future directions.
Nature reviews. Clinical oncology. Jul 2013;10(7):411-424.
22.
 Berggren P, Steineck G, Adolfsson J, et al. p53 mutations in urinary bladder cancer. British
journal of cancer. Jun 01 2001;84(11):1505-1511.
23.
 Hellweg CE, Spitta LF, Henschenmacher B, Diegeler S, Baumstark-Khan C. Transcription
Factors in the Cellular Response to Charged Particle Exposure. Frontiers in oncology. 2016;6:61.
24.
 Laramore GE. Role of particle radiotherapy in the management of head and neck cancer. Current
opinion in oncology. May 2009;21(3):224-231.
25.
 Maalouf M, Alphonse G, Colliaux A, et al. Different mechanisms of cell death in radiosensitive
and radioresistant p53 mutated head and neck squamous cell carcinoma cell lines exposed to
carbon ions and x-rays. International journal of radiation oncology, biology, physics. May 01
2009;74(1):200-209.
26.
 Kobayashi D, Oike T, Shibata A, et al. Mitotic catastrophe is a putative mechanism underlying
the weak correlation between sensitivity to carbon ions and cisplatin. Scientific reports. Jan 16
2017;7:40588.
27.
 Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines
sensitivity to PD-1 blockade in non-small cell lung cancer. Science. Apr 03 2015;348(6230):124-
128.
28.
 Chabanon RM, Pedrero M, Lefebvre C, Marabelle A, Soria JC, Postel-Vinay S. Mutational
Landscape and Sensitivity to Immune Checkpoint Blockers. Clinical cancer research : an official
journal of the American Association for Cancer Research. Sep 01 2016;22(17):4309-4321.
29.
 Gottlieb CF, Gengozian N. Radiation dose, dose rate, and quality in suppression of the humoral
immune response. Journal of immunology. Oct 1972;109(4):719-727.
30.
 Schaue D, Comin-Anduix B, Ribas A, et al. T-cell responses to survivin in cancer patients
undergoing radiation therapy. Clinical cancer research : an official journal of the American
Association for Cancer Research. Aug 01 2008;14(15):4883-4890.
31.
 Nesslinger NJ, Sahota RA, Stone B, et al. Standard treatments induce antigen-specific immune
responses in prostate cancer. Clinical cancer research : an official journal of the American
Association for Cancer Research. Mar 01 2007;13(5):1493-1502.
32.
 Small EJ, Lance RS, Gardner TA, et al. A Randomized Phase II Trial of Sipuleucel-T with
Concurrent versus Sequential Abiraterone Acetate plus Prednisone in Metastatic Castration-
Resistant Prostate Cancer. Clinical cancer research : an official journal of the American
Association for Cancer Research. Sep 01 2015;21(17):3862-3869.
33.
 Ardiani A, Gameiro SR, Kwilas AR, Donahue RN, Hodge JW. Androgen deprivation therapy
sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation
of the apoptotic pathway. Oncotarget. Oct 15 2014;5(19):9335-9348.
34.
 Pu Y, Xu M, Liang Y, et al. Androgen receptor antagonists compromise T cell response against
prostate cancer leading to early tumor relapse. Science translational medicine. Apr 06
2016;8(333):333ra347.
35.
 Horvat TZ, Adel NG, Dang TO, et al. Immune-Related Adverse Events, Need for Systemic
Immunosuppression, and Effects on Survival and Time to Treatment Failure in Patients With
Melanoma Treated With Ipilimumab at Memorial Sloan Kettering Cancer Center. Journal of
clinical oncology : official journal of the American Society of Clinical Oncology. Oct 01
2015;33(28):3193-3198.
P a g e | 21


CC9938 CLINICAL RESEARCH PROTOCOL 10/19/2020
Fred Hutch IRB
Approved
8/22/2023
36.
 Weber JS, Hodi FS, Wolchok JD, et al. Safety Profile of Nivolumab Monotherapy: A Pooled
Analysis of Patients With Advanced Melanoma. Journal of clinical oncology : official journal of
the American Society of Clinical Oncology. Mar 2017;35(7):785-792.
37.
 Attard G, Reid AH, Yap TA, et al. Phase I clinical trial of a selective inhibitor of CYP17,
abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone
driven. Journal of clinical oncology : official journal of the American Society of Clinical
Oncology. Oct 1 2008;26(28):4563-4571.
38.
 Sander FE, Rydstrom A, Bernson E, et al. Dynamics of cytotoxic T cell subsets during
immunotherapy predicts outcome in acute myeloid leukemia. Oncotarget. Feb 16
2016;7(7):7586-7596.
39.
 Huang AC, Postow MA, Orlowski RJ, et al. T-cell invigoration to tumour burden ratio associated
with anti-PD-1 response. Nature. May 04 2017;545(7652):60-65.
P a g e | 22

ICF_000.pdf: 
 
 
Official Title: 
Radiation Enhancement of Local and Systemic Anti-
Prostate Cancer Immune Responses   
NCT number: 
NCT03649841 
Document Type:  
Informed Consent Form 
Date of the 
Document: 
2/8/2021 
 
 


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 1 of 15  
 
University Of Washington 
Seattle Cancer Care Alliance 
Consent to take part in a research study: 
RADIATION ENHANCEMENT OF LOCAL AND SYSTEMIC                         
ANTI-PROSTATE CANCER IMMUNE RESPONSES 
Principal Investigator: Jing Zeng, MD University of Washington; Fred Hutchinson Cancer 
Research Center. 206-598-4100 
Emergency number (24 hours): 206-598-6190  
Ask for the Radiation Oncologist on-call. 
Important things to know about this study. 
 
You are invited to participate in a research study. The purpose of this research is to study 
the effects of neutron radiation therapy on your immune system and whether it helps 
stimulate body’s own immune system to help fight prostate cancer. 
 
People who agree to join the study will be asked to attend 3-4 clinic visits over 6 months. 
The study involves physical exam, blood draw, optional tumor biopsy, routine blood test 
for prostate specific antigen (PSA) and CT scan.  
We do not know if neutron radiation therapy would help stimulate a larger immune 
response inside the body in castration sensitive prostate cancer (CSPC) condition, and it 
could even make your condition/disease worse. Neutron radiation therapy could cause 
side effects such as fatigue, itchy skin, diarrhea, urinary irritation, rectal irritation, 
inability to have children etc. as described below in this form.  
You do not have to join this study. You can choose to receive standard methods to treat 
CSPC instead of participating in this study. We will give you details about the purposes, 
procedures, risks and possible benefits related to this study. We will explain other choices 
that you have. We will also give you any other information that you need in order to 
make an informed decision about joining this study.  
Following is a more complete description of this study. Please read this description 
carefully. You can ask any questions you want to help you decide whether to join the 
study. If you join this study, we will give you a signed copy of this form to keep for 
future reference.  
IRO received 01/20/21


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 2 of 15  
We invite you to join this research study. 
We invite you to join this research study because you have CSPC. Up to 30 people will 
join this study. 
Research is not the same as treatment or medical care. The purpose of a research study is 
to answer scientific questions.  
You do not have to be in the study. You are free to say “yes” or “no”, or to drop out after 
joining. If you say “no,” you would have no penalty or loss of benefits. Whatever you 
decide, your regular medical care would not change.  
Why are we doing this study? 
We are doing this study to examine the effects of neutron radiation therapy on your 
immune system. Adding a short course of high intensity radiation early in the treatment 
course may improve the anti-tumor environment by acting as a “vaccine”. Neutron 
radiation treatment has a higher relative biological effectiveness (RBE) compared to 
standard photon radiation, which essentially means the neutron radiation is more 
damaging than the standard radiation. Neutron radiation treatment is the experimental 
aspect of this research study.  We want to know whether the radiation can help improve 
your treatment. Patients with metastatic prostate cancer often receive radiation for a 
variety of reasons, most commonly- 
1) To help relieve a symptom caused by a tumor (such as a tumor in a bone causing pain); 
or 
2) To help prevent a future problem that will be caused by a tumor (such as a tumor in a 
bone that can cause a bone fracture); or 
3) To potentially help control the cancer by helping kill as many cancer cells as possible 
when there are only a limited number of metastatic sites in the body.   
 
Therefore, it is currently clinical acceptable to both give radiation to patients with 
metastatic prostate cancer and to just give androgen deprivation therapy (ADT).  
 
ADT is a standard treatment for CSPC. Your prostate cancer cells grow because of male 
hormones (androgens), so reducing levels of androgens would help combat and slow the 
spread of prostate cancer cells. Recent studies have shown that the addition of abiraterone 
(Zytiga®), a pill that blocks an enzyme your body requires to make testosterone, can 
improve survival compared to ADT alone. A steroid, called prednisone, must be taken 
with the abiraterone to reduce its side-effects. Not much is known about the immune 
system effects of abiraterone plus prednisone, but there is data that suggests abiraterone 
may create an immune response against prostate cancer.  
There are 2 groups of participants in this study. We will give different treatments to 
different groups, and compare the results. This is how we hope to find out if radiation is 
helpful.  


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 3 of 15  
In this study, we use a computer program to decide which treatment to give. If you join 
this study, you would not be allowed to choose the treatment. You would have a 1-in-1 
chance of receiving radiation. 
What research tests, procedures, and treatments are done in this study? 
• Group 1 participants would receive- ADT + abiraterone + prednisone  
• Group 2 participants would receive- ADT + abiraterone + prednisone+ Radiation 
Participants in both Group 1 and Group 2 would receive the following tests and 
procedures at specified time points- 
 
•   Medical History and Physical Exam- Before you begin abiraterone + prednisone, 
1 and 4 months after start of abiraterone + prednisone 
•   Review your performance status- Before you begin abiraterone + prednisone, 1 
and 4 months after start of abiraterone + prednisone  
•  CT scans or MRI or PET/CT – CT scan is preferable but MRI or PET/CT is also 
acceptable. Required only before you begin abiraterone + prednisone treatment.  
• 
PSA (prostate specific antigen) level- Before you begin abiraterone + 
prednisone, 1 and 4 months after start of abiraterone + prednisone and every 4 
weeks until 6 months after start of abiraterone. 
•   Research Blood draw- We will be collecting your blood at specific time-points 
for us to study changes in your body’s immune response.  We will make attempts 
to collect blood during the times you would normally get blood drawn (to check 
for your blood counts and PSA) to minimize the amount of needle pricks you 
receive.   
 
 
3 Collection Time-points:  
• Before you begin abiraterone + prednisone treatment  
• 1 month after you start abiraterone + prednisone treatment  
• 4 months after you start abiraterone + prednisone treatment 
 
We will collect 9 tubes of blood, or about 5-6 tablespoons each collection. If we 
are not able to combine a research blood draw with a clinical blood draw, 
arrangements will have to be made to return to SCCA or UWMC for the research 
blood collection. Each blood draw visit would be 10 minutes or less. We will make 
every attempt to make this convenient for you. 
 
 


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 4 of 15  
Neutron Radiation Treatment (Group 2) 
If you are randomized to the Abiraterone + Prednisone + Radiation Arm, you will start 
radiation treatment around the time you start abiraterone + prednisone. You can have up 
to 3 lesions, or cancerous spots, radiated at the same time. Being on this treatment arm 
would require extra visits to accommodate the radiation treatment.  
 
Visits  
• CT-based simulation for radiation treatment planning  
• 1st dose of radiation  
• 2nd dose of radiation 
• 3rd dose of radiation  
 
Your radiation oncologist may spread out your treatment doses to 5 doses if he/she is 
concerned for any side-effects you may experience. The total dose of neutron radiation 
you will receive will range between 6-10 gray units (radiation dose is measured in terms 
of how your tissue absorbs energy). Each radiation treatment will be a visit that is 30 
minutes or less.  Neutron radiation is FDA approved for treating cancers, and has been in 
use at the University Of Washington Medical Center for over 40 years.  It is covered by 
Medicare and many other insurance plans.  
 
Another way to find out what will happen to you during the study is to read the chart 
below. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 5 of 15  
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                                                      
 
 
 
 
 
 
           
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Symbol Key 
 9 tubes of blood for research purposes  
 Optional research biopsy of a non-radiated tumor 
 
BEGIN 
Androgen Deprivation Therapy (ADT) 
        ≤ 2 months 
STUDY ENROLLMENT 
       ≤ 30 days 
 Research Blood Draw 
 
R A N D O M I Z A T I O N 
  
START  
Abiraterone + Prednisone 
Radiation Treatment # 1 
Radiation Treatment # 2 
Radiation Treatment # 3   
 
START 
 Abiraterone + Prednisone 
         1 month 
1 month 
Research Blood Draw 
 Research Blood Draw 
       3 months 
3 months 
 Research Blood Draw 
 Research Blood Draw 
CONTINUE  
Abiraterone + Prednisone  
PSA and Survival Data  
every 4 weeks for another  
2 months 
CONTINUE  
Abiraterone + Prednisone  
PSA and Survival Data  
every 4 weeks for another  
2 months 
STUDY COMPLETION 
STUDY COMPLETION 
ARM 1 
Abiraterone + Prednisone 
ARM 2    
                     
Abiraterone + Prednisone + 
Radiation 


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 6 of 15  
How long would you stay in this study? 
If you join this study, you would stay in this study for about 6 months after starting 
abiraterone + prednisone regimen. 
Doctors could take you out of this study at any time. This would happen if: 
• 
They think it is in your best interest not to continue in the study. 
• 
You are not able or willing to follow study procedures. 
• 
The whole study is stopped.   
If you withdraw from the study for any reason, previously collected information would 
remain in the study records and would be included in the analysis of results. This 
information could not be removed from the study records.  
What are the side effects (risks)? 
In this part of the consent form, we describe the side effects we expect from the tests and 
treatments in this study. Neutron radiation treatment could cause side effects we do not 
know about yet. We carefully watch everyone in the study for side effects.   
If you join this study, we would tell you if we discover new side effects that could affect 
you.  
On both Group 1 and Group 2 of the study, the treatment of ADT plus Abiraterone + 
Prednisone you receive is not experimental and is the care that you would normally 
receive, regardless of being enrolled on this trial. 
Side effects may be mild or very serious. Medicines could be given to help lessen side 
effects. Many side effects go away soon after you stop receiving neutron radiation. In 
some cases, side effects can last a long time or never go away.  
Research blood collection 
• Bruising or minor swelling at the site of needle injection 
• Light headedness or dizziness 
• Pressure from the tourniquet (rubber band around your upper arm to increase blood 
flow)  
Drug risks 
• Abiraterone Acetate 
o Likely side effects of abiraterone acetate are (≥5% of patients): 
 joint swelling or discomfort  


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 7 of 15  
 hypokalemia  
 edema  
 muscle discomfort  
 hot flush  
 diarrhea  
 urinary tract infection  
 cough 
 hypertension  
 arrhythmia  
 urinary frequency  
 nocturia  
 dyspepsia  
 upper respiratory tract infection 
o Less likely side effects of abiraterone acetate are (<1% of patients):  
 aspartate aminotransferase increased  
 alanine aminotransferase increased  
 urosepsis  
 cardiac failure  
• Prednisone 
o Likely side effects of prednisone are: 
 fluid retention 
 alteration in glucose tolerance 
 elevation in blood pressure 
 behavioral and mood changes 
 increased appetite 
 weight gain 


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 8 of 15  
Prednisone is given as a low dose medication in combination with abiraterone acetate 
in order to manage the potential side effects of abiraterone, such as low potassium or 
high blood pressure.   
Radiation risks 
 
If you are randomized to Group 2 (ADT plus Abiraterone + Prednisone + Radiation), 
then you will receive neutron radiation treatment, which is the experimental aspect of this 
research study. The amount of radiation is equivalent to what you would receive with 
standard photon radiation. Exact toxicity depends on the site of treatment and your 
radiation oncologist will discuss this with you.  
• General 
o Fatigue  
o Itchy Skin 
o Hair loss inside radiation field 
• Head and neck treatment 
o Dry mouth 
o Inflammation of membranes  
o Difficulty swallowing  
o Nausea 
o Tooth decay 
• Chest treatment  
o Difficulty swallowing 
o Nausea 
o Lung damage causing shortness of breath, cough, or fever 
• Abdomen treatment 
o Nausea/vomiting 
o Diarrhea 
• Pelvis treatment 
o Diarrhea 
o Urinary irritation  
o Rectal irritation causing bleeding or urgency 
 
Reproductive risks  
Inability to have children - The effects of neutron radiation treatment on fathering a child 
is also unknown. Men who join this study must also agree to use one or more forms of 


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 9 of 15  
effective and acceptable birth control from the time this form is signed until at least 4 
months after the last dose of neutron radiation treatment. 
 
CT scans 
CT scans in this research study will expose you to radiation. Everyone receives a small 
amount of radiation every day called “background radiation”. This radiation is natural 
and comes from space, air, water, soil, and the food you eat. Each year you are exposed 
to about 3 milliSieverts (mSv) of this background radiation. A milliSievert is a unit of 
radiation dose. For comparison, the estimated radiation dose from each of these scans is 
listed below.  This does not include the dose to subjects who will receive neutron therapy. 
The risk to your health from this level of radiation exposure is too low to be detectable 
and may be nonexistent. 
 
· CT Chest: 7 mSv 
· CT Abdomen: 8 mSv 
· CT Pelvis: 6 mSv 
Non-physical risks 
If you join this study, non-physical risks are: 
• 
You might not be able to work. 
What are the benefits? 
We do not know if this study would help you. We are trying to compare abiraterone + 
prednisone alone versus abiraterone + prednisone + radiation to see its effects on people 
with CSPC. You might get better if you receive neutron radiation treatment, but your 
condition could stay the same or even get worse. We do not know which treatment is 
more effective for advanced CSPC. We hope the information from this study will help 
other people with CSPC in the future. 
You have other choices besides this study. 
You do not have to join this study. You are free to say “yes” or “no”. Your regular 
medical care would not change if you decide to say “no”.  
You have other choices for treatment.  Each of these choices has risks and benefits. You 
should talk to your doctor or healthcare provider about these choices.   
Other choices include: Standard Treatment; If your doctor recommends abiraterone + 
prednisone and/or neutron radiation, you can still receive those treatments as part of your 
regular care without being on this clinical trial. 
Enrollment in this study may exclude you from other research studies.  


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 10 of 15  
Protecting Privacy as an Individual and the Confidentiality of Personal 
Information  
If you join this study, some people or organizations might need to look at your medical 
records and research records for quality assurance or data analysis. They include: 
• 
Researchers involved with this study. 
• 
Institutional Review Boards (IRB), including the Fred Hutchinson Cancer 
Research Center IRB. An IRB is a group that reviews the study to protect the 
rights and welfare of research participants. 
• 
Fred Hutchinson Cancer Research Center, University of Washington, Seattle 
Children’s, and Seattle Cancer Care Alliance. 
• 
US National Institutes of Health, National Cancer Institute, Office for Human 
Research Protections, Food and Drug Administration, and other regulatory 
agencies as required. 
We will do our best to keep personal information confidential. But we cannot 
guarantee total confidentiality.  Personal information may be given out if required by 
law.  For example, workplace safety rules may require health workers to contact you 
about lab tests. Or a court may order study information to be disclosed. Such cases 
are rare. 
We will not use personal information in any reports about this study, such as journal 
articles or presentations at scientific meetings. 
 
If you join this study, information about your participation would be made part of your 
permanent medical record. This information would include a copy of this consent form. If 
an insurance company or employer or anyone else were authorized to see your medical 
record, they would see a copy of this consent form.  
Would we pay you if you join this study? 
There is no payment for being in this study. 
 
Would you have extra costs if you join this study?  
Under normal circumstances you would have physician appointments and undergo 
similar lab and scan procedures as you would on this study. If you join this study, you or 
your insurance company would have to pay for the costs of standard treatment in this 
study. While on study you will be responsible for meeting your insurance plan co-
pay/deductible requirements. If you are randomized to Group 2 of the study, you or your 
insurance company would have to pay for the costs to receive neutron radiation 
treatment.  


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 11 of 15  
You would not be billed for: 
• Up to 3 Research blood collection (if not done during standard blood draws) and 
supplies  
• Up to 2 Optional research biopies 
You may incur additional medical care costs associated with the medical management of 
side effects experienced while you are receiving abiraterone + prednisone and/or 
radiation.  
What if you get sick or hurt after you join this study? 
 
For a life threatening problem, call 911 right away or seek help immediately.  Contact 
your study doctor when the medical emergency is over or as soon as you can.    
 
For all other medical problems or illness related to this research, immediately contact 
206-598-6190 Radiation Oncologist on-call. They will treat you or refer you for 
treatment.  You or your health insurance will have to pay for the treatment. There are no 
funds to pay you for a research-related injury, added medical costs, loss of a job, or other 
costs to you or your family.  State or national law may give you rights to seek payment 
for some of these expenses.  You do not waive any right to seek payment by signing this 
consent form. 
 
You or your insurer will be billed for treatment of problems or complications that result 
from your condition or from standard clinical care. 
You would not lose any legal right to seek payment for treatment if you sign this form. 
What will my information and/or tissue samples be used for? 
Your information and tissue samples (such as blood and tumor cells) will be used for the 
purposes of this study. 
Your tissue samples might help researchers develop new products. This research could be 
done by for-profit companies. There is no plan to share with you any revenue generated 
from products developed using your tissue samples. 
During this study, if the researchers learn new information that may be important to your 
general health or to your disease or condition, they will share that information with you.  
In addition, be aware that by agreeing to participate in this study, your information or 
tissue samples could be used for future research studies or sent to other investigators for 
future research studies without additional consent from you. These future research studies 
will be reviewed by an oversight group known as an institutional review board if required 
by law. The information that identifies you will first be removed from your information 
or tissue samples. If you do not want your information or tissue samples to be used for 
future research studies without your consent, you should not participate in this study. 


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 12 of 15  
Your rights 
• 
You do not have to join this study. You are free to say “yes” or “no”.  
• 
If you get sick or hurt in this study, you do not lose any of your legal rights to seek 
payment by signing this form. 
• 
During the study, we might learn new information that you need to know. For 
example, some information may affect your health or well-being. Other information 
might make you change your mind about being in this study. If we learn these kinds 
of information, we would tell you. 
• 
If you join this study, you would not have to stay in it. You could stop at any time 
(even before you start). Your regular medical care would not change. You would 
have no penalty for stopping, but it would be better not to join the study if you think 
that you would change your mind later.   
• 
If you decide to drop out, we would want you to tell the study doctor. The doctor 
could tell you about the effects of stopping neutron radiation treatment. You and the 
doctor could talk about the follow-up care and testing that would help the most.  
• 
Before you leave the study, the doctor might ask you to obtain permission to record 
treatment related data up to 6 months post-treatment.   
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.  
Your responsibilities 
If you join this study, you would have some responsibilities.  
• 
Follow the schedule of study visits and procedures. 
• 
Take study medications as directed.  
• 
Prevent pregnancy. 
• 
Tell us about side effects.    


 
057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 13 of 15  
For more information 
If you have questions or concerns about this study, you can talk to your doctor 
anytime. Other people you could talk to are listed below. 
 
If you have questions about: 
 
Call: 
This study (including 
complaints and requests for 
information) 
 
206-598-4100 (Dr. Jing Zeng) 
206-598-8239 (Priya Vissamraju, Research 
Coordinator) 
 
If you get sick or hurt in this 
study 
 
206-598-4100 (Dr. Jing Zeng) 
Your rights as a research 
participant 
 
206-667-5900 or email irodirector@fredhutch.org 
(Director of Institutional Review Office, Fred 
Hutchinson Cancer Research Center) 
206-543-0098 (Human Subjects Division, University 
of Washington) 
Your bills and health insurance 
coverage 
 
206-606-6226 Seattle Cancer Care Alliance 
Financial Services 
206-598-1950 UW Medical Center Financial 
Services 
 
 
Emergency number (24 hours): (206) 598-6190 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 14 of 15 
Tumor Biopsy (Optional) 
The additional research biopsy part of this study is completely optional. You can still 
participate in the main part of this study without undergoing the research biopsy. This 
will only apply to patients randomized to the radiation arm (Group 2), although that 
determination will be made after obtaining your willingness to undergo the biopsy. There 
are two tumor biopsies for patients who consent, pre-radiation treatment and post-
radiation treatment (2-4 weeks after radiation). Biopsied tissue of an untreated site after 
radiation therapy for castration sensitive prostate cancer has never been studied in this 
setting. It is important to understand that the results of this research biopsy are not 
designed specifically to help you. This is an opportunity for us to generate more 
information regarding your type of cancer. Information from this research will not be 
included in your medical record. For those who give permission for the research tumor 
biopsy, the biopsy will be scheduled prior to radiation treatment and within 4-weeks after 
your radiation treatment. 
There will be a separate procedure consent form that will outline the risks associated with 
the area planned for biopsy. You and your insurance company will not be charged for this 
research procedure.  
Read each question and think about your choice. When you decide on each question, 
please circle YES or NO. 
Do you agree to donate your tissue to study cancer? 
(Circle one) 
YES 
NO 


057IRBform_ModelConsentClin / Version 13.00 / 10-19-2020 / Page 15 of 15 
Signatures 
Please sign below if you:  
•
have read this form (or had it read to you);
•
had the opportunity to ask any questions you have;
•
had the opportunity to discuss the research with the person obtaining consent;
and
•
agree to participate in this study.
Participant (age 14+): 
Printed Name 
Signature 
Date 
If you served as an interpreter or impartial witness during the consent process, sign 
below to indicate you attest to the accuracy of the presentation and the participant’s 
apparent understanding of and willingness to participate in the research. 
Impartial Witness or Interpreter: 
Printed Name 
Signature 
Date 
Researcher’s statement 
I have discussed the research study, including procedures and risks, with the person 
signing above. A copy of the signed consent form will be given to the participant. 
Person obtaining consent signature: 
Printed Name 
Signature 
Date 
Protocol: CC9938 
Current consent version date:  8/31/19 
Previous consent version date:  
Copies to:  
FHCRC IRB Approval  
02/08/2021 
Document Released Date