Cabazitaxel With Abiraterone Versus Abiraterone Alone Randomized Trial for Extensive Disease Following Docetaxel: The CHAARTED2 Trial
Phase: PHASE2
Conditions: Castration Levels of Testosterone, Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma in the Soft Tissue, Prostate Carcinoma Metastatic in the Bone, Stage IV Prostate Adenocarcinoma AJCC v7
Sponsor: ECOG-ACRIN Cancer Research Group

 
EA8153 
1 
Cabazitaxel with Abiraterone versus Abiraterone alone 
Randomized Trial for Extensive Disease following 
Docetaxel: the CHAARTED2 Trial 
STUDY CHAIR: Christos Kyriakopoulos, M.D. 
STUDY STATISTICIAN: Yu-Hui Chen, MPH, M.S. 
STUDY CO-CHAIR: Glenn Liu, M.D. 
IMAGING CO-CHAIR: Robert Jeraj, Ph.D. 
IMAGING STATISTICIAN: Fenghai Duan, Ph.D. 
TRANSLATIONAL SCIENCE CO-CHAIR: Jun Luo, Ph.D. 
TRANSLATIONAL SCIENCE CO-CHAIR: Emmanuel Antonarakis, M.B.B.Ch 
PROSTATE SUB-COMMITTEE CHAIR: Glenn Liu, M.D. 
GU COMMITTEE CHAIR: Michael Carducci, M.D.  
Version Date:  September 17, 2021 
 
STUDY PARTICIPANTS 
 
ACTIVATION DATE 
ALLIANCE / Alliance for Clinical Trials in Oncology  
February 8, 2018 
NRG / NRG Oncology 
 
 
SWOG / SWOG 
 
Addendum #1 
 
 
Addendum #2 
Addendum #3 
NCTN GROUP STUDY CHAMPIONS 
 
Addendum #4 
ALLIANCE: Yousef Zakharia, M.D. 
 
 
SWOG: Paul Corn, M.D., Ph.D. 
 
 
 
Agents 
IND# 
NSC# 
Supply 
Abiraterone acetate 
IND Exempt Study 
748121 
Commercially Available 
Cabazitaxel 
794609 
Genzyme 
Prednisone 
10023 
Commercially Available 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
2 
Table of Contents 
Schema ...................................................................................................................... 6 
1. Introduction ........................................................................................................ 7 
1.1 
Background ............................................................................................... 7 
1.2 
Rationale for selected approach and trial design ..................................... 8 
1.3 
Therapeutic agents ................................................................................... 8 
1.4 
Rationale for correlative studies ............................................................. 10 
1.5 
Rationale for Tobacco Use Assessment .................................................. 11 
2. Objectives ......................................................................................................... 13 
2.1 
Primary Objective .................................................................................... 13 
2.2 
Secondary Objectives .............................................................................. 13 
2.3 
Exploratory Objectives ............................................................................ 13 
3. Selection of Patients ......................................................................................... 15 
3.1 
Eligibility Criteria ..................................................................................... 15 
3.2 
NaF PET/CT Optional Sub-Study Eligibility Criteria ................................. 18 
4. CTEP Registration Procedures ........................................................................... 20 
4.1 
Protocol Number ..................................................................................... 23 
4.2 
Investigator Identification ....................................................................... 23 
4.3 
Patient Identification .............................................................................. 24 
4.4 
Eligibility Verification .............................................................................. 24 
4.5 
Stratification Factors ............................................................................... 24 
4.6 
Additional Requirements ........................................................................ 24 
4.7 
Instructions for Patients who Do Not Start Assigned Protocol Treatment26 
5. Treatment Plan ................................................................................................. 27 
5.1 
Administration Schedule ......................................................................... 27 
5.2 
Adverse Event Reporting Requirements ................................................. 28 
5.3 
Dose Modifications ................................................................................. 34 
5.4 
Supportive Care ....................................................................................... 39 
5.5 
Patient Reported Outcome Measures: Tobacco Use Assessment 
(Optional) ................................................................................................ 39 
5.6 
Duration of Therapy ................................................................................ 41 
5.7 
Duration of Follow-up ............................................................................. 41 
6. Measurement of Effect ..................................................................................... 42 
6.1 
Antitumor Effect – Solid Tumors ............................................................. 42 
6.2 
Serological Response .............................................................................. 50 
6.3 
Endpoint Definitions ............................................................................... 50 
7. Study Parameters .............................................................................................. 51 
7.1 
Therapeutic Parameters .......................................................................... 51 
7.2 
Biological Sample Submissions ............................................................... 53 
8. Drug Formulation and Procurement ................................................................. 54 
8.1 
Abiraterone acetate ................................................................................ 54 
8.2 
Cabaxitaxel .............................................................................................. 55 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
3 
8.3 
Prednisone .............................................................................................. 57 
9. Statistical Considerations .................................................................................. 60 
9.1 
Primary Objective .................................................................................... 60 
9.2 
Study Design ............................................................................................ 60 
9.3 
Statistical Consideration for Secondary Objectives ................................ 61 
9.4 
Statistical Considerations for Exploratory Objectives ............................. 62 
9.5 
Gender and Ethnicity .............................................................................. 63 
9.6 
Study Monitoring .................................................................................... 63 
9.7 
Tobacco Use Assessment ........................................................................ 63 
10. Imaging Research Study .................................................................................... 64 
10.1 NaF PET/CT Imaging ................................................................................ 64 
11. Submission of Biospecimens for Research ....................................................... 67 
11.1 Sample Collection and Submission Schedule .......................................... 67 
11.2 Submissions to the ECOG-ACRIN Central Biorepository and Pathology 
Facility (CBPF) .......................................................................................... 67 
11.3 Submissions to Johns Hopkins University ............................................... 68 
11.4 ECOG-ACRIN Sample Tracking System .................................................... 69 
11.5 Use of Specimens in Research ................................................................ 70 
11.6 Sample Inventory Submission Guidelines ............................................... 70 
12. Laboratory Research Studies ............................................................................ 71 
12.1 Association of Androgen-Receptor Splice Variant 7 Messenger RNA (AR-
V7) Presence in Circulating Tumor Cells and Response to Treatment and 
Outcome .................................................................................................. 71 
12.2 Lab Data Transfer Guidelines .................................................................. 71 
13. Electronic Data Capture .................................................................................... 72 
14. Patient Consent and Peer Judgment ................................................................ 72 
15. References ........................................................................................................ 72 
Appendix I  Patient Thank You Letter ...................................................................... 74 
Appendix II  Patient Pill Calendar ............................................................................ 75 
Appendix III  ECOG Performance Status .................................................................. 80 
Appendix IV  EA8153 Collection and Shipping Kit Order Instructions ..................... 81 
Appendix V  EA8153 Cabazitaxel Study Drug Request Form and EA8153 
Investigational Product Destruction Record Download Instructions ............... 82 
 Appendix VI  Ancillary for Tobacco Use Assessment: EAQ16T ............................... 83 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
4 
 
STUDY CHAIR 
Christos Kyriakopoulos, M.D. 
University of Wisconsin Carbone Cancer Center 
600 Highland Avenue, K4/623 
Madison, WI 53792 
Phone: (608) 263-7107 
Fax: (608) 265-5146 
uwcccgu@medicine.wisc.edu 
 
STUDY CHAIR LIAISON (SCL) 
Mary Jane Staab, RN 
University of Wisconsin Carbone Cancer Center 
GU Oncology Research Program 
600 Highland Avenue, K4/623 
Madison, WI 53792 
Phone: (608) 263-7107 
Fax: (608) 265-5146 
uwcccgu@medicine.wisc.edu 
 
 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
5 
CANCER TRIALS SUPPORT UNIT (CTSU) CONTACT INFORMATION 
For regulatory requirements: 
For patient enrollments: 
For study data 
submission: 
Regulatory documentation must 
be submitted to the CTSU via the 
Regulatory Submission Portal. 
Regulatory Submission Portal: 
(Sign in at www.ctsu.org, and 
select the Regulatory Submission 
sub-tab under the Regulatory 
tab.) 
Institutions with patients waiting 
that are unable to use the Portal 
should alert the CTSU Regulatory 
Office immediately at 1-866-651-
2878 to receive further instruction 
and support. 
Contact the CTSU Regulatory 
Help Desk at 1-866-651-2878 for 
regulatory assistance. 
Please refer to the patient enrollment 
section of the protocol for instructions on 
using the Oncology Patient Enrollment 
Network (OPEN) which can be accessed 
at https://www.ctsu.org/OPEN_SYSTEM/ 
or https://OPEN.ctsu.org. 
Contact the CTSU Help Desk with any 
OPEN-related questions at 
ctsucontact@westat.com. 
Data collection for this 
study will be done 
through Medidata 
Rave and the ECOG-
ACRIN Systems for 
Easy Entry of Patient 
Reported Outcomes 
(EASEE-PRO) 
system. Please see 
the data submission 
section of the protocol 
for further instructions.  
Do not submit study 
data or forms to CTSU 
Data Operations. Do 
not copy the CTSU on 
data submissions.  
The most current version of the study protocol and all supporting documents must be downloaded 
from the protocol-specific Web page of the CTSU Member Web site located at https://www.ctsu.org.  
Access to the CTSU members’ website is managed through the Cancer Therapy and Evaluation 
Program - Identity and Access Management (CTEP-IAM) registration system and requires user log on 
with CTEP-IAM username and password.  
For clinical questions (i.e., patient eligibility or treatment-related) Contact the Study PI of the 
Coordinating Group. 
For non-clinical questions (i.e., unrelated to patient eligibility, treatment, or clinical data 
submission) contact the CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com. All calls and 
correspondence will be triaged to the appropriate CTSU representative.  
The CTSU Web site is located at   https://www.ctsu.org 
 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
6 
Schema 
Accrual Goal = 210 patients
Cycle = 21 days
R
A
N
D
O
M
I
Z
E
Androgen deprivation 
Abiraterone acetate 1000mg once daily (PO)
Cabazitaxel 25mg/m2 on day 1 every 21 days for 
up to 6 cycles. (IV)
Prednisone 5mg twice daily (PO)
Androgen deprivation
Abiraterone acetate 1000mg once daily (PO)
Prednisone 5mg twice daily (PO)
Radiographic or 
symptomatic progression
1.
All patients will continue androgen depravation as per standard of care.
2.
All patients will receive Prednisone 5mg twice daily
3.
Randomization 1:1 between the two arms
L
O
N
G
-
T
E
R
M
F
O
L
L
O
W
-
U
P
Arm B
Arm A
Strat factors:
• ECOG performance 
status of 0 vs. 1-2
• Time from initiation of 
ADT to the development 
of CRPC of   12 vs. >12 
months 
• Visceral metastases 
(non-bone, non-lymph 
node) status of Yes vs. 
No
 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
7 
1. 
Introduction 
1.1 
Background 
Prostate cancer is the most common cancer diagnosis and the second cancer-
leading cause of death in men, with a 2016 estimate of 180,890 new cases and 
26,120 deaths in the United States [1]. For patients with localized disease, 
treatment options for definitive therapy include surgery and/or radiation therapy. 
Approximately 1/3 of these men will experience disease recurrence as evidenced 
by a rise in their serum PSA [2]. While some men may still be cured with salvage 
therapies, most will eventually develop metastatic disease [3]. Ever since the 
critical role of androgens in stimulating prostate cancer growth was established 
[4], androgen deprivation therapy (ADT) with either surgical or medical castration 
remains the primary approach to the treatment of hormone-sensitive prostate 
cancer (HSPC). Although most men will initially respond to ADT [5], all patients 
will eventually develop castrate-resistant prostate cancer (CRPC), evidenced by 
increase in serum PSA, new clinical metastases, progression of existing 
metastases and/or worsening symptoms [6]. Over the last few years, several new 
agents have been added to our therapeutic armory [7]; however, the duration of 
response is limited, indicating the need for new treatment strategies that will 
further delay disease progression, prolong survival and improve quality of life. 
The E3805 (CHAARTED) trial showed that the addition of 6 cycles of docetaxel 
to standard androgen deprivation therapy (ADT) significantly improved 
progression-free survival (PFS) and overall survival (OS) compared to standard 
ADT alone in men with metastatic hormone-sensitive prostate cancer [8]. The 
hypothesis behind that trial was that significant level of resistance to ADT is 
already present at the time of initial presentation in patients with metastatic 
disease and that this phenomenon is proportional to the extent of tumor burden; 
hence, decreasing burden may prolong benefit. In addition, a proportion of 
patients are too frail to receive docetaxel at the time of development of CRPC 
and as such they might miss the window to receive treatment with an active 
agent; thus, early treatment might confer additional benefit. Further, preclinical 
studies have shown a synergistic effect between ADT and taxanes, with 
significant delay in development of CRPC [9, 10] and as such combination of 
ADT and docetaxel can prolong survival. Seven hundred ninety previously 
untreated, hormone-naïve metastatic prostate cancer patients were randomly 
assigned to ADT plus docetaxel or to ADT alone. After a median follow-up of 
28.9 months, there was a significant OS benefit of 13.6 months for the group that 
received chemohormonal therapy [median OS 57.6 vs. 44.0 months; HR 0.61 
(0.47-0.80); p<0.001]. Further, the median time to clinical progression was 
significantly longer with chemohormonal therapy [33.0 vs. 19.8 months; HR 0.61 
(0.50-0.75); p<0.001] and so the median time to CRPC development [20.2 vs. 
11.7 months; HR 0.61 (0.51-0.72); p<0.001]. When patients were stratified based 
on tumor burden, the addition of docetaxel was found to significantly prolong the 
OS in the high-volume group [49.2 vs. 32.2 months, HR 0.60 (0.45-0.81); 
p<0.001]; however, despite a trend towards an improved survival in the low-
volume group, that was not statistically significant at the time of follow-up.  Based 
on those results, ADT in combination with docetaxel is considered the new 
standard of care for that patient population, as long as they are suitable for 
treatment with docetaxel chemotherapy.  

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
8 
In addition to the CHAARTED data, the STAMPEDE trial also showed a survival 
benefit from the early introduction of docetaxel chemotherapy in hormone-
sensitive prostate cancer patients [11]. In that trial, patients were assigned to 
multiple regimens including ADT, docetaxel and zoledronic acid. The primary 
endpoint of OS was significantly improved for the patients treated with ADT plus 
docetaxel vs. patients that only received ADT (median OS 81 vs. 71 months, HR 
0.78, 95% CI 0.66-0.93; p=0.006). In the subgroup analysis based on the 
presence or absence of metastatic disease, survival was significantly prolonged 
for patients with metastasis (median OS 60 vs. 45 months, HR 0.76, 95% CI 
0.62-0.92; p=0.005); however, there was insufficient number of deaths in the 
group without radiographic metastasis to allow firm conclusions. 
The above phase III trials have established the role of chemohormonal therapy 
for patients with newly diagnosed metastatic prostate cancer, at least in those 
patients with high-volume disease. However, it is unknown if the same strategy in 
the castration-resistant setting –especially in patients that have previously 
received docetaxel for ADT-naïve disease- will be of any value. 
1.2 
Rationale for selected approach and trial design 
Despite the significant improvement in outcome by the addition of docetaxel to 
ADT, eventually all patients will develop castration-resistant disease. Current 
therapies in that setting include second-line androgen receptor (AR) signaling 
pathway inhibitors, chemotherapy, immunotherapy, radium-223, palliative 
radiation or supportive care. Upon development of castration-resistant disease, 
patients can receive sequential treatment with docetaxel rechallenge, 
cabazitaxel, sipuleucel-T, abiraterone acetate with prednisone, enzalutamide or 
radium-223. All the above agents have been approved for the treatment of 
metastatic CRPC patients based on studies that showed prolongation of survival; 
however, the clinical benefit of each of those therapies in patients that have 
previously received treatment with docetaxel in the hormone-naïve setting is 
unknown. Currently, the most commonly used agents in that setting are second-
line androgen receptor signaling pathway inhibitors, such as abiraterone acetate. 
We hypothesize that a second course of chemohormonal therapy with 
cabazitaxel and abiraterone acetate will result in suppression of resistant clones 
to abiraterone acetate that are already present. This trial aims to evaluate 
whether the addition of 6 cycles of cabazitaxel to abiraterone acetate can prolong 
the PFS of patients with metastatic CRPC that have received first-line 
chemohormonal therapy with docetaxel for HSPC. In addition, even though this 
trial will be underpowered to confirm a prolongation in OS, it will seek preliminary 
data of OS benefit from the addition of cabazitaxel to abiraterone acetate. Finally, 
this trial will include exploratory biomarkers of disease resistance and response 
to therapy. 
1.3 
Therapeutic agents 
Abiraterone acetate (Zytiga TM, Jannsen Biotech Inc, Horsham, PA) is an oral 
CYP17 inhibitor indicated in combination with prednisone for the treatment of 
patients with metastatic castration-resistant prostate cancer. Two randomized 
phase III trials have shown survival benefit in the pre- and post-docetaxel setting, 
respectively. The COU-AA-301 double-blind placebo-controlled trial enrolled 
1195 patients with metastatic CRPC that had previously received docetaxel 
chemotherapy for castration-resistant disease [12]. Patients received abiraterone 
acetate 1000 mg PO daily in combination with prednisone 5 mg PO twice daily 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
9 
vs. placebo plus prednisone 5 mg PO twice daily. Median PFS was significantly 
improved in favor of the abiraterone acetate group vs. the placebo group (5.6 vs. 
3.6 months; p<0.001). The median OS was also significantly prolonged for the 
patients that received abiraterone acetate with prednisone vs. placebo and 
prednisone [15.8 months (95% CI 14.8-17.0) vs. 11.2 months (10.4-13.1); HR 
0.74, 95% CI 0.64-0.86; p<0.0001) [13]. Similarly, the COU-AA-302 double-blind 
placebo-controlled trial that examined the role of abiraterone acetate in 
combination with prednisone in chemotherapy-naïve patients showed an 
improvement in the median radiographic PFS in favor of abiraterone acetate 
(16.5 vs. 8.3 months; HR 0.53; 95% CI 0.45-0.62; p<0.001) [14]. Further, there 
was a significant survival benefit in favor of the abiraterone acetate arm as well 
[34.7 months (95% CI 32.7-36.8) vs. 30.3 months (28.7-33.3; HR 0.81, 95% CI 
0.70-0.93; p=0.0033)] [15]. The most common side effects of abiraterone acetate 
in those trials were fluid retention, hypertension, hypokalemia and liver-function 
abnormalities. Based on those two studies abiraterone acetate in combination 
with prednisone was approved for the treatment of metastatic CRPC patients 
both before and after treatment with docetaxel. 
In addition to the second-line AR signaling pathway inhibitors, chemotherapy is 
also an attractive treatment option, especially when rapid disease control is 
required. Cabazitaxel (Jevtana TM, Genzyme, Paris, France) is a microtubule 
inhibitor indicated in combination with prednisone for treatment of patients with 
metastatic CRPC previously treated with a docetaxel-containing treatment 
regimen. Cabazitaxel is administered intravenously every 3 weeks at a 
recommended dose of 25 mg/m2. The TROPIC phase III clinical trial compared 
cabazitaxel to mitoxantrone in patients with metastatic CRPC that had previously 
progressed on treatment with docetaxel [16]. Seven hundred fifty-five men were 
randomized 1:1 to cabazitaxel 25 mg/m2 IV every 3 weeks vs. mitoxantrone 12 
mg/m2 IV every 3 weeks. All patients received prednisone 10 mg PO daily. The 
median survival was significantly improved for the groups that received 
cabazitaxel [15.1 months (95% CI 2.4-3.0) vs. 12.7 months (11.6-13.7); 
p<0.0001] and so the median PFS [2.8 months (95% CI 2.4-3.0) vs. 1.4 months 
(95% CI 1.4-1.7); p<0.0001]. The most common clinically significant grade 4 or 
higher side effects of cabazitaxel were neutropenia and diarrhea. Based on those 
results cabazitaxel was granted approval by FDA for treatment of metastatic 
CRPC in that setting. 
The current paradigm for treatment of castration-resistant prostate cancer is 
sequential exposure to drugs that have shown activity in CRPC. Several ongoing 
and completed clinical trials have combined the aforementioned agents in the 
castration-resistant setting. A phase 1/2 trial of cabazitaxel in combination with 
abiraterone acetate showed that the combination of full dose cabazitaxel and 
abiraterone acetate is well tolerated and demonstrated antitumor activity in the 
post-docetaxel setting [17]. Twenty-seven patients previously treated with 
docetaxel were enrolled. The median number of cycles with cabazitaxel was 7 
(range 1-21) and the median PSA-PFS was 6.9 months (95% CI 4.1-10.2 
months). Twelve patients achieved a PSA response (PSA response rate 46%; 
95% CI 26.6-66.4%) and 3 out of 14 patients (21%) with measurable disease 
achieved a partial response per RECIST 1.1. Most common side effects were 
grade > 3 neutropenia (15 patients; 55%; 1 patient with febrile neutropenia), 
fatigue (4 patients; 15%) and sepsis (3 patients; 11%). These data support the 
use of combination treatment, given their acceptable safety profile and enhanced 
efficacy. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
10 
1.4 
Rationale for correlative studies 
1.4.1 
Association of androgen-receptor splice variant 7 messenger RNA 
(AR-V7) presence in circulating tumor cells and response to treatment 
and outcome. 
It has been shown that the detection of androgen-receptor splice 
variant 7 messenger RNA (AR-V7) in circulating tumor cells from 
patients with CRPC is associated with resistance to abiraterone 
acetate and enzalutamide, whereas it is not associated with 
resistance to taxanes [18, 19]. In an initial study, a total of 31 patients 
treated with enzalutamide and 31 patients treated with abiraterone 
acetate were prospectively evaluated for the presence of AR-V7, 
which was detected in 39% and 19%, respectively [18]. Among 
patients receiving abiraterone acetate, AR-V7 positivity was 
associated with lower PSA response rate (0% vs. 68%; p=0.004), and 
shorter PSA PFS (1.3 months vs. not reached; p<0.001), clinical or 
radiographic PFS (2.3 months vs. not reached; p<0.001) and OS 
(10.6 months vs. not reached; p=0.006). However, in patients treated 
with taxanes, it appears that the presence of AR-V7 does not confer 
resistance to treatment [19]. From the 37 taxane-treated patients, 17 
(46%) were tested positive for AR-V7. Both AR-V7 positive and 
negative patients had similar responses to therapies, assessed both 
by PSA and radiographically. A pooled analysis of patients from both 
studies showed that outcomes were superior with taxanes compared 
to enzalutamide or abiraterone acetate in AR-V7-positive men (PSA 
responses 41% vs. 0%; p<0.001), PSA PFS (HR 0.19; 95% CI 0.07-
0.52; p=0.001) and radiographic PFS (HR 0.21; 95% CI 0.007-0.59; 
p=0.003). Our aim is to prospectively examine a) whether patients 
positive for AR-V7 at baseline have a longer radiographic or clinical 
PFS to the combination of cabazitaxel and abiraterone acetate vs. 
abiraterone acetate alone; b) whether the addition of cabazitaxel can 
change the AR-V7 status of patients who are positive at study 
registration; and c) whether the addition of cabazitaxel to abiraterone 
acetate has any impact on future development of AR-V7 positivity at 
the time of disease progression. 
1.4.2 
Characterize the pharmacodynamic changes and response to 
treatment using NaF PET/CT. 
The clinical course of metastatic prostate cancers is largely restricted 
to bone, with predominantly osteoblastic metastases. However, there 
is currently no validated tool to assess treatment response in patients 
with metastatic prostate cancer to the bone. One of the most 
promising PET imaging agents for detection of bone metastasis in 
prostate cancer is 18F-Sodium fluoride (NaF). NaF PET/CT is a more 
specific and sensitive tool that allows quantitative determination of 
change in functional disease burden to therapy.  NaF PET/CT 
repeatability and responsiveness in patients with metastatic 
castration-resistant prostate cancer to bone treated with an 
antimicrotubule directed agent or AR-directed therapies has been 
previously evaluated [20]. In this study, we will prospectively examine 
whether the addition of cabazitaxel to abiraterone acetate can 
improve the overall response as well as the percentage of responding 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
11 
lesions compared to abiraterone acetate alone in support of our 
hypothesis. NaF PET/CT scans will be analyzed with innovative 
image analysis technique, termed Quantitative Total Bone Imaging 
(QTBI), developed at the University of Wisconsin [21, 22]. NaF 
PET/CT image analysis will be performed at AIQ Solutions, Inc., using 
the FDA 510(K) cleared software. 
1.5 
Rationale for Tobacco Use Assessment 
NOTE: 
Please refer to Appendix VI for EAQ16T references. 
A significant proportion of cancer patients are current smokers at the time of 
cancer diagnosis, [1-5] and there are known risks associated with continued 
smoking following cancer diagnosis. These include decreased survival time; 
increased complications from surgery, radiation, and chemotherapy; and 
increased risk of second primary tumors [6,-11] As such, the National 
Comprehensive Cancer Network (NCCN), the American Association of Cancer 
Research (AACR) and the American Society of Clinical Oncology (ASCO) have 
identified persistent smoking as a modifiable risk factor and recommend 
cessation counseling for cancer patients who smoke. Although evidence-based 
guidelines for treating tobacco dependence exist, [12] they have not yet been 
well-integrated into cancer care settings. Moreover, knowledge regarding the 
scope and patterns of tobacco use among cancer patients is limited. 
Tobacco use following a cancer diagnosis compromises treatment outcomes but 
is not well understood. About 10% to 30% of cancer patients are smoking at the 
time of diagnosis, [1-4, 14, 1 5] and the majority of cancer patients who smoke at 
diagnosis continue to smoke following diagnosis [3, 16]. Quitting smoking upon 
cancer diagnosis may improve cancer treatment effectiveness, reduce risk of 
recurrence and of developing new primary tumors, [9,11,17-21] and improve 
chances of survival [1,22-24]. Conversely, continuing to smoke may result in 
diminished QOL [1, 25, 26], treatment delays and increased treatment 
complications [2, 6–8, 22, 27–34]. 
Tobacco use following a cancer diagnosis may compromise patient reported 
outcomes. It is hypothesized that smoking may be used as a means of reducing 
symptom burden among cancer patients, which may be a barrier to smoking 
cessation. Relatedly, research has shown that cancer patients who are smoking 
experience more difficulty with physical and psychological symptom control, 
compared to nonsmokers [35–38]. Research is needed to examine how symptom 
levels differ, by tobacco use and exposure and how tobacco use changes may 
affect reported symptom burden. 
National initiatives emphasize the importance of identifying tobacco use in cancer 
care settings.  Smoking status was designated as a core objective in the 2010 
federal government “Meaningful Use” electronic health record documentation [39, 
40]. In 2013, the American Association for Cancer Research (AACR) released 
guidelines emphasizing the provision of tobacco cessation services to cancer 
patients [41]. The American Society of Clinical Oncology (ASCO) recommends 
cessation counseling to all smokers by their second oncology visit as a core 
quality indicator [42]. The National Comprehensive Cancer Network (NCCN) 
published Smoking Cessation guidelines to formalize these initiatives [43]. 
Integrated, evidence-based services are needed during cancer care. The USPHS 
Practice Guidelines recommend that evidence-based tobacco treatment be 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
12 
delivered to all smokers in health care settings, yet little progress has been made 
to integrate these guidelines into cancer care [44]. This is unfortunate, as 
cessation closer to the time of diagnosis results in a higher likelihood for 
continued abstinence [1,45-48] effective interventions exist, [1,45-48] and many 
cancer patients who smoke want to quit smoking[45,46,49,50]. Little work has 
been done to explore the delivery and effectiveness of tobacco treatment among 
racial/ethnic minority cancer patients who are at elevated risk of continued 
smoking [51-53]. 
Tobacco use is often not being assessed or intervened upon during cancer care.  
Recent surveys of oncologists and of clinical practices at comprehensive cancer 
centers and community oncology settings demonstrate that assessment of 
tobacco dependence is lacking [54-57]. During treatment, most cancer patients 
do not get assistance with smoking cessation support.58–60 Tobacco use 
assessments and cessation support have not been incorporated in most 
cooperative group clinical trials [61]. No one has assessed cancer patients’ 
reports of their oncology providers’ assistance behaviors. 
The NCI-AACR Cancer Patient Tobacco Use Assessment Task Force developed 
the Cancer Patient Tobacco Use [1-4,13,14]. Questionnaire (C-TUQ). We 
propose that administering selected C-TUQ items to participants enrolling in 8 
Phase II and Phase III ECOG ACRIN (EA) therapeutic trials will add value to 
parent trial research questions by advancing the field. Specifically, among 
patients with varied cancers (tobacco-related and non tobacco-related) and 
cancer treatments, we will administer C-TUQ questions at EA trial enrollment and 
3 and 6 month follow-up. 
We have the following aims: 
1. Treatment toxicity: To determine the effects of tobacco, operationalized as 
combustible tobacco (1a), other forms of tobacco (1b), and environmental 
tobacco exposure (ETS) (1c) on provider-reported cancer-treatment toxicity 
(adverse events (both clinical and hematologic) and dose modifications). 
2. Symptom burden: To determine the effects of tobacco on patient-reported 
physical symptoms and psychological symptoms. 
3. Cessation patterns and treatment: To examine quitting behaviors and 
behavioral counseling/support and cessation medication utilization. 
4. Trial outcomes: To explore the effect of tobacco use and exposure on 
treatment duration and relative dose intensity, and on therapeutic benefit, of 8 
selected EA trials. 
The findings will advance the nascent field of tobacco use in the context of 
cancer care by: 1) longitudinal assessment of cigarette smoking, other forms of 
tobacco use and secondhand smoke exposure at trial enrollment and at 3 and 6 
month follow-up; 2) increase knowledge about the effects of tobacco use and 
exposure on treatment toxicity, physical and psychological symptoms and 3) 
oncology provider delivery,  and 4) patient’s perceptions of stigma and utilization 
of behavioral and pharmacological treatment of tobacco dependence.   Finally, 
the use of this assessment would provide a unique additional value to the 
hypothesis of this trial, by allowing investigation of previously unanswered 
questions about the effects of tobacco use and exposure on trial adherence and 
outcomes among patients with smoking-related and non-smoking related cancers 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
13 
2. 
Objectives 
2.1 
Primary Objective 
2.1.1 
To assess whether the addition of 6 cycles of cabazitaxel to 
abiraterone acetate in patients with CRPC that have previously 
received docetaxel and ADT for HSPC can improve PFS compared to 
abiraterone acetate alone. 
2.2 
Secondary Objectives 
2.2.1 
To assess whether the addition of 6 cycles of cabazitaxel to 
abiraterone acetate in patients with CRPC that have previously 
received docetaxel and ADT for HSPC can increase the percentage of 
change in PSA from baseline to week 12 of treatment as well as the 
maximum decline in PSA that occurs at any point after treatment 
compared to abiraterone acetate alone. 
2.2.2 
To assess whether the addition of 6 cycles of cabazitaxel to 
abiraterone acetate in patients with CRPC that have previously 
received docetaxel for HSPC can prolong time to PSA progression 
compared to abiraterone acetate alone. 
2.2.3 
To assess whether the addition of 6 cycles of cabazitaxel to 
abiraterone acetate in patients with CRPC that have previously 
received docetaxel for HSPC can improve radiographic response (per 
RECIST 1.1) compared to abiraterone acetate alone. 
2.2.4 
To assess whether the addition of 6 cycles of cabazitaxel to 
abiraterone acetate in patients with CRPC that have previously 
received docetaxel and ADT for HSPC can prolong the overall 
survival (OS) compared to abiraterone acetate alone. 
2.2.5 
To assess safety and tolerability of the combination of 6 cycles of 
cabazitaxel and abiraterone acetate. 
2.3 
Exploratory Objectives 
2.3.1 
AR-V7 Biomarker Objectives 
2.3.1.1 
To examine whether patients with circulating tumor cells 
(CTCs) positive for AR-V7 at baseline have a longer 
radiographic or clinical PFS to the combination of 
cabazitaxel and abiraterone acetate vs. abiraterone 
acetate alone. 
2.3.1.2 
To examine whether the addition of cabazitaxel to 
abiraterone acetate can change the AR-V7 status of 
patients who are positive at study registration. 
2.3.1.3 
To examine whether the addition of cabazitaxel to 
abiraterone acetate has any impact on future development 
of AR-V7 positivity at the time of disease progression. 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
14 
2.3.2 
Imaging Objectives 
2.3.2.1 
To assess if the changes in total tumor burden from 
baseline to week 12 as assessed with NaF PET/CT will 
differ between two arms. 
2.3.2.2 
To correlate total tumor burden at the baseline as 
assessed with NaF PET/CT with the PFS. 
2.3.2.3 
To correlate heterogeneity of response from baseline to 
week 12 as assessed with NaF PET/CT with the PFS. 
2.3.3 
Tobacco Use Objectives 
2.3.3.1 
To determine the effects of tobacco, operationalized as 
combustible tobacco (1a), other forms of tobacco (1b), and 
environmental tobacco exposure (ETS) (1c) on provider-
reported cancer-treatment toxicity (adverse events (both 
clinical and hematologic) and dose modifications). 
2.3.3.2 
To determine the effects of tobacco on patient-reported 
physical symptoms and psychological symptoms. 
2.3.3.3 
To examine quitting behaviors and behavioral 
counseling/support and cessation medication utilization. 
2.3.3.4 
To explore the effect of tobacco use and exposure on 
treatment duration, relative dose intensity, and therapeutic 
benefit. 
NOTE: 
Tobacco Use objectives described above are ancillary for 
the Tobacco Use Assessment project approved by NCI. A 
combined analysis of the data from the selected ECOG-
ACRIN trials is planned. Data collected from the tobacco 
use assessment in each parent study will not be analyzed 
and reported in the clinical study report. 
 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
15 
3. 
Selection of Patients 
Each of the criteria in the checklist that follows must be met in order for a patient to be 
considered eligible for this study. Use the checklist to confirm a patient’s eligibility. For 
each patient, this checklist must be photocopied, completed and maintained in the 
patient’s chart.  
In calculating days of tests and measurements, the day a test or measurement is 
done is considered Day 0. Therefore, if a test is done on a Monday, the Monday 
four weeks later would be considered Day 28.  
ECOG-ACRIN Patient No. ____________________________ 
Patient’s Initials (L, F, M) _______________________ 
Physician Signature and Date ___________________ 
NOTE: 
CTEP Policy does not allow for the issuance of waivers to any protocol 
specified criteria 
(http://ctep.cancer.gov/protocolDevelopment/policies_deviations.htm). 
Therefore, all eligibility criteria listed in Section 3 must be met, without 
exception. The registration of individuals who do not meet all criteria listed in 
Section 3 can result in the participant being censored from the analysis of the 
study, and the citation of a major protocol violation during an audit.  All 
questions regarding clarification of eligibility criteria must be directed to the 
Group's Executive Officer (EA.ExecOfficer@jimmy.harvard.edu) or the 
Group's Regulatory Officer (EA.RegOfficer@jimmy.harvard.edu). 
NOTE: 
Institutions may use the eligibility checklist as source documentation if it has 
been reviewed, signed, and dated prior to registration/randomization by the 
treating physician. 
NOTE: 
Institutions are not required to participate in the optional NaF PET/CT sub-
study. 
3.1 
Eligibility Criteria 
3.1.1 
Inclusion Criteria 
3.1.1.1 
Age ≥ 18 years. 
3.1.1.2 
Histologically confirmed diagnosis of prostate cancer 
(adenocarcinoma of the prostate). 
3.1.1.3 
Previous chemotherapy with at least 3 cycles of docetaxel 
for hormone-sensitive metastatic prostate cancer. 
3.1.1.4 
Metastatic disease as evidenced by the presence of soft 
tissue and/or bone metastases on imaging studies 
(CT/MRI of abdomen/pelvis, bone scintigraphy or NaF 
PET/CT). 
3.1.1.5 
Ability to swallow abiraterone acetate tablets as a whole. 
3.1.1.6 
All patients must be receiving standard of care androgen 
deprivation treatment (surgical castration versus LHRH 
agonist or antagonist treatment); subjects receiving LHRH 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
16 
agonist or antagonist must continue treatment throughout 
the time on this study. 
3.1.1.7 
Patients must have castrate serum level of testosterone of 
< 50 ng/dL (< 1.73 nmol/L), confirmed ≤ 4 weeks prior to 
randomization. 
Serum testosterone:________ Date of test:______ 
3.1.1.8 
Patients must have progressive disease while receiving 
androgen deprivation therapy defined by any one of the 
following as per the Prostate Cancer Clinical Trials 
Working Group 3 (PCWG3) criteria for PSA, measurable 
disease or non-measurable (bone) disease [23] during 
treatment with ADT: 
3.1.1.8.1 
PSA:  At least two consecutive rises in 
serum PSA, obtained at a minimum of 1-
week intervals, with the final value ≥ 1.0 
ng/mL, confirmed ≤ 4 weeks prior to 
randomization 
PSA:________ Date of test:______.  
OR 
3.1.1.8.2 
Measurable disease (by RECIST 1.1):   
> 20% increase in the sum of the longest 
diameters of all measurable lesions or the 
development of new measurable lesions.  
The short axis of a target lymph node must 
be more that 15 mm to be assessed for 
change in size. 
OR 
3.1.1.8.3 
Non-measurable (bone) disease: The 
appearance of two or more new areas of 
uptake on bone scan (or NaF PET/CT) 
consistent with metastatic disease 
compared to previous imaging during 
castration therapy. The increased uptake of 
pre-existing lesions on bone scan will not be 
taken to constitute progression, and 
ambiguous results must be confirmed by 
other imaging modalities (e.g. X-ray, CT or 
MRI). Clinical decisions about response or 
progression will be based on CT and bone 
scans. 
3.1.1.9 
Patients may or may not have been treated previously with 
a nonsteroidal antiandrogen, such as flutamide, 
bicalutamide or nilutamide. For patients previously treated 
with an antiandrogen, they must be off treatment for at 
least 4 weeks (for flutamide) or 6 weeks (for bicalutamide 
or nilutamide) prior to registration and must have shown 
PSA progression after discontinuing the anti-androgen. 
Rev. Add#2 
Rev. Add#2 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
17 
3.1.1.10 
Patients must have an ECOG performance status of 0, 1, 
or 2. 
3.1.1.11 
Adequate hematologic and renal function as evidenced by 
the following baseline laboratory values ≤ 4 weeks prior to 
randomization: 
3.1.1.11.1 
ANC ≥ 1500/mm3 
ANC:________ Date of test:______ 
3.1.1.11.2 
Hgb ≥ 9.0 gr/dL 
Hgb:________ Date of test:______ 
3.1.1.11.3 
Platelets ≥ 100,000/mm3 
Platelet count:________ Date of 
test:______ 
3.1.1.11.4 
Creatinine < 2.0 mg/dL 
Creatinine:________ Date of test:______ 
3.1.1.12 
Patients must be informed of the experimental nature of 
the study and its potential risks, and must sign an IRB-
approved written informed consent form indicating such an 
understanding. 
3.1.1.13 
Patients with resected or irradiated brain metastases or 
those treated with stereotactic radiation therapy are eligible 
to enroll, provided that they do not require treatment with 
steroids that exceeds 10 mg of prednisone daily or 
equivalent.  
3.1.1.14 
Sexually active males must use an accepted and effective 
method of double barrier contraception (vasectomy must 
be combined with a physical barrier method) or abstain 
from sexual intercourse for the duration of their 
participation in the study and for 26 weeks after the last 
dose of study drug. 
3.1.2 
Exclusion Criteria 
3.1.2.1 
Any prior chemotherapy or AR-directed therapy for CRPC, 
(e.g. docetaxel, cabazitaxel, mitoxantrone, abiraterone 
acetate, ketoconazole, or enzalutamide). Previous 
treatment with radium-223, sipuleucel-T, or other 
immunotherapy-based treatment is allowed.  
3.1.2.2 
Pure small cell or other variant (non-adenocarcinoma) 
prostate cancer histology for which treatment with 
abiraterone would not be considered appropriate. 
3.1.2.3 
Patients may not be receiving other therapeutic 
investigational agents or be receiving concurrent 
anticancer therapy other than standard androgen 
deprivation therapy. Concurrent treatment with agents to 
prevent skeletal-related events (such as zoledronic acid or 
denosumab) will be allowed as long as it was initiated prior 
Rev. Add#2 
Rev. Add#2 
Rev. Add#2 
Rev. Add#3 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
18 
to study registration or there are plans to initiate it after 
cycle 2 day 1. 
3.1.2.4 
Any medical condition for which prednisone (corticosteroid) 
is contraindicated.  
3.1.2.5 
Chronic liver disease or abnormal liver function at baseline:  
3.1.2.5.1 
If total bilirubin is > ULN (NOTE: in subjects 
with Gilbert’s syndrome, if total bilirubin is  
> ULN, measure direct and indirect bilirubin 
and if direct bilirubin is within normal range, 
subject may be eligible) or  
3.1.2.5.2 
Alanine (ALT) or aspartate (AST) 
aminotransferase > 1.5xULN. 
3.1.2.6 
Active infection requiring treatment with antibiotics. 
3.1.2.7 
History of adrenal insufficiency or hypoaldosteronism. 
3.1.2.8 
Myocardial infarction or arterial thrombotic event ≤ 6 
months of randomization, heart failure of New York Heart 
Association Class II or higher, uncontrolled angina, severe 
uncontrolled ventricular arrhythmia.  
3.1.2.9 
External beam radiation therapy ≤ 2 weeks of registration. 
3.1.2.10 
Prior history of allergic reactions to G-CSF.  
3.1.2.11 
Prior history of allergic reactions to docetaxel and/or to 
medications formulated with polysorbate 80. 
3.1.2.12 
History of active malignancy. Patients with a history of 
cancer that has been adequately treated and are free of 
disease recurrence for 3 years or more are allowed to 
participate. Patients with non-melanoma skin cancers or 
carcinoma in situ of the bladder that have been adequately 
excised are eligible to participate. 
3.1.2.13 
Life expectancy of < 12 months at screening. 
3.1.2.14 
Grade ≥ 2 neuropathy. 
3.1.2.15 
Uncontrolled hypertension (systolic BP ≥ 160 mmHg or 
diastolic BP ≥ 100 mmHg). Patients with a history of 
hypertension are allowed to enroll provided blood pressure 
is controlled with anti-hypertensive treatment. 
3.2 
NaF PET/CT Optional Sub-Study Eligibility Criteria 
3.2.1 
Inclusion Criteria 
3.2.1.1 
Ability to lie still for imaging. 
3.2.1.2 
Weight ≤ 300 lbs. (due to equipment specifications) 
3.2.1.3 
Metastatic disease confined predominantly to the bones. 
 
Rev. Add#2 
Rev. Add#2 
Rev. Add#2 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
19 
 
 
 
Physician Signature 
 
Date 
OPTIONAL: 
This signature line is provided for use by institutions wishing to 
use the eligibility checklist as source documentation. 
 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
20 
4. 
CTEP Registration Procedures 
Food and Drug Administration (FDA) regulations and National Cancer Institute (NCI) 
policy require all individuals contributing to NCI-sponsored trials to register and to renew 
their registration annually.  To register, all individuals must obtain a Cancer Therapy 
Evaluation Program (CTEP) Identity and Access Management (IAM) account 
(https://ctepcore.nci.nih.gov/iam).  In addition, persons with a registration type of 
Investigator (IVR), Non-Physician Investigator (NPIVR), or Associate Plus (AP) (i.e., 
clinical site staff requiring write access to OPEN, RAVE, or TRIAD or acting as a primary 
site contact) must complete their annual registration using CTEP’s web-based 
Registration and Credential Repository (RCR) (https://ctepcore.nci.nih.gov/rcr).  
Documentation requirements per registration type are outlined in the table below 
Documentation Required 
IVR 
NPIVR 
AP 
A 
FDA Form 1572 
 
 
Financial Disclosure Form 
 
 
 
NCI Biosketch (education, training, employment, 
license, and certification) 
 
 
 
HSP/GCP training 
 
 
 
Agent Shipment Form (if applicable) 
 
CV (optional) 
 
 
 
An active CTEP-IAM user account and appropriate RCR registration is required to 
access all CTEP and CTSU (Cancer Trials Support Unit) websites and applications.  In 
addition, IVRs and NPIVRs must list all clinical practice sites and IRBs covering their 
practice sites on the FDA Form 1572 in RCR to allow the following: 
• 
Added to a site roster 
• 
Assigned the treating, credit, consenting, or drug shipment (IVR only) tasks in OPEN 
• 
Act as the site-protocol PI on the IRB approval 
Additional information can be found on the CTEP website at < 
https://ctep.cancer.gov/investigatorResources/default.htm >.  For questions, please 
contact the RCR Help Desk by email at < RCRHelpDesk@nih.gov >. 
CTSU Registration Procedures 
This study is supported by the NCI Cancer Trials Support Unit (CTSU). 
IRB Approval: 
Each investigator or group of investigators at a clinical site must obtain IRB approval for 
this protocol and submit IRB approval and supporting documentation to the CTSU 
Rev. Add#2 
Rev. Add#3 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
21 
Regulatory Office before they can be approved to enroll patients.  Assignment of site 
registration status in the CTSU Regulatory Support System (RSS) uses extensive data 
to make a determination of whether a site has fulfilled all regulatory criteria including but 
not limited to the following: 
• 
An active Federal Wide Assurance (FWA) number 
• 
An active roster affiliation with the Lead Network or a participating organization 
• 
A valid IRB approval 
• 
Compliance with all protocol specific requirements. 
In addition, the site-protocol Principal Investigator (PI) must meet the following criteria: 
• 
Active registration status 
• 
The IRB number of the site IRB of record listed on their Form FDA 1572 
An active status on a participating roster at the registering site.. 
Sites participating on the NCI CIRB initiative that are approved by the CIRB for this study 
are not required to submit IRB approval documentation to the CTSU Regulatory Office. 
For sites using the CIRB, IRB approval information is received from the CIRB and 
applied to the RSS in an automated process. Signatory Institutions must submit a Study 
Specific Worksheet for Local Context (SSW) to the CIRB via IRBManager to indicate 
their intent to open the study locally.  The CIRB’s approval of the SSW is then 
communicated to the CTSU Regulatory Office.  In order for the SSW approval to be 
processed, the Signatory Institution must inform the CTSU which CIRB-approved 
institutions aligned with the Signatory Institution are participating in the study. 
Downloading Site Registration Documents: Site registration forms may be 
downloaded from the EA8153 protocol page located on the CTSU members’ website. 
• 
Go to https://www.ctsu.org and log in to the members’ area using your CTEP-IAM 
username and password 
• 
Click on the Protocols tab in the upper left of your screen 
• 
Either enter the protocol # in the search field at the top of the protocol tree, or  
• 
Click on the By Lead Organization folder to expand 
• 
Click on the ECOG-ACRIN link to expand, then select trial protocol EA8153 
• 
Click on LPO Documents, select the Site Registration documents link, and download 
and complete the forms provided. 
Requirements for EA8153 Site Registration: 
• 
IRB approval (For sites not participating via the NCI CIRB; local IRB documentation, 
an IRB-signed CTSU IRB Certification Form, Protocol of Human Subjects Assurance 
Identification/IRB Certification/Declaration of Exemption Form, or combination is 
accepted )  
Requirements for NaF PET/CT Sub-Study Participation: 
NOTE: 
Institutions are not required to participate in the optional NaF PET/CT 
sub-study. 
• 
EA8153 sites that wish to participate in the NaF PET/CT sub-study will be required to 
meet PET/CT Scanner Qualification requirements and approval. Please refer to the 
NaF Site Imaging Manual for guidance on the PET/CT Scanner Qualification 
process. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
22 
• 
The NaF Site Imaging Manual is available for download on the CTSU members’ 
website under the ‘Miscellaneous’ tab. 
If your site is interested in NaF PET/CT sub-study participation, please contact Diana 
Ewen, dewen@acr.org to find out if your site is approved or what your site needs to do 
prior to enrolling a patient onto the sub-study 
Submitting Regulatory Documents 
Submit required forms and documents to the CTSU Regulatory Office via the Regulatory 
Submission Portal, where they will be entered and tracked in the CTSU RSS. 
Regulatory Submission Portal: www.ctsu.org  (members’ area) → Regulatory Tab → 
Regulatory Submission 
When applicable original documents should be mailed to: 
CTSU Regulatory Office 
1818 Market Street, Suite 3000 
Philadelphia, PA 19103 
Institutions with patients waiting that are unable to use the Portal should alert the CTSU 
Regulatory Office immediately at 1-866-651-2878 in order to receive further instruction 
and support. 
Required Protocol Specific Regulatory Documents 
1. Copy of IRB Informed Consent Document. 
NOTE:  
Any deletion or substantive modification of information concerning risks or 
alternative procedures contained in the sample informed consent 
document must be justified in writing by the investigator and approved by 
the IRB. 
2. A.  CTSU IRB Certification Form. 
 
Or 
B.  Signed HHS OMB No. 0990-0263 (replaces Form 310). 
 
Or 
 
C.  IRB Approval Letter 
NOTE: 
The above submissions must include the following details: 
• 
Indicate all sites approved for the protocol under an assurance 
number. 
• 
OHRP assurance number of reviewing IRB 
• 
Full protocol title and number 
• 
Version Date 
• 
Type of review (full board vs. expedited) 
• 
Date of review. 
• 
Signature of IRB official 
Checking Your Site’s Registration Status: 
You can verify your site registration status on the members’ section of the CTSU 
website. 
• 
Go to https://www.ctsu.org and log in to the members’ area using your CTEP-IAM 
username and password 
• 
Click on the Regulatory tab 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
23 
• 
Click on the Site Registration tab 
• 
Enter your 5-character CTEP Institution Code and click on Go 
NOTE: 
The status given only reflects compliance with IRB documentation and 
institutional compliance with protocol-specific requirements as outlined by the 
Lead Network. It does not reflect compliance with protocol requirements for 
individuals participating on the protocol or the enrolling investigator’s status 
with the NCI or their affiliated networks. 
Patient Enrollment 
Patients must not start protocol treatment prior to randomization. 
Treatment must start within ten working days after randomization. 
Patients who consent to participate in the NaF PET/CT scan sub-study must 
complete baseline NaF PET/CT scan prior to start of treatment. 
NOTE: 
Institutions are not required to participate in the optional NaF PET/CT 
sub-study. 
NOTE: 
Patient participation in the Tobacco Use Assessment sub-study is 
optional. 
Patient enrollment will be facilitated using the Oncology Patient Enrollment Network 
(OPEN). OPEN is a web-based registration system available on a 24/7 basis.  To access 
OPEN, the site user must have an active CTEP-IAM account (check at 
<https://ctepcore.nci.nih.gov/iam>) and a 'Registrar' role on either the LPO or 
participating organization roster. Registrars must hold a minimum of an AP registration 
type. 
All site staff will use OPEN to enroll patients to this study.  It is integrated with the CTSU 
Enterprise System for regulatory and roster data and, upon enrollment, initializes the 
patient in the Rave database. OPEN can be accessed at https://open.ctsu.org or from 
the OPEN tab on the CTSU members’ side of the website at https://www.ctsu.org. To 
assign an IVR or NPIVR as the treating, crediting, consenting, drug shipment (IVR only), 
or investigator receiving a transfer in OPEN, the IVR or NPIVR must list on their Form 
FDA 1572 in RCR the IRB number used on the site’s IRB approval. 
Prior to accessing OPEN, site staff should verify the following: 
• 
All eligibility criteria have been met within the protocol stated timeframes.  
• 
All patients have signed an appropriate consent form and HIPAA authorization form 
(if applicable). 
NOTE: 
The OPEN system will provide the site with a printable confirmation of 
registration and treatment information. Please print this confirmation for your 
records.  
Further instructional information is provided on the OPEN tab of the CTSU members’ 
side of the CTSU website at https://www.ctsu.org or at https://open.ctsu.org.  For any 
additional questions contact the CTSU Help Desk at 1-888-823-5923 or 
ctsucontact@westat.com. 
4.1 
Protocol Number  
4.2 
Investigator Identification  
• 
Institution and affiliate name 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
24 
• 
Investigator’s name 
4.3 
Patient Identification  
• 
Patient’s initials (first and last) 
• 
Patient’s Hospital ID and/or Social Security number 
• 
Patient demographics 
• 
Gender 
• 
Birth date (mm/yyyy) 
• 
Race 
• 
Ethnicity 
• 
Nine-digit ZIP code 
• 
Method of payment 
• 
Country of residence 
4.4 
Eligibility Verification  
Patients must meet all of the eligibility requirements listed in Section 3. 
4.5 
Stratification Factors 
• 
ECOG performance status of 0 vs. 1-2 
• 
Time from initiation of ADT to the development of CRPC of ≤ 12 vs. >12 
months 
• 
Visceral metastases (non-bone, non-lymph node) status of Yes vs. No 
4.6 
Additional Requirements  
4.6.1 
Patients must provide a signed and dated, written informed consent 
form. 
NOTE: 
Copies of the consent are not collected by the ECOG-
ACRIN Operations Office – Boston. 
4.6.2 
Biological specimens are to be submitted for defined laboratory 
research studies and/or future undefined research per patient consent 
as outlined in Section 10. 
4.6.3 
Data collection for this study will be done exclusively through the 
Medidata Rave clinical data management system. Access to the trial 
in Rave is granted through the iMedidata application to all persons 
with the appropriate roles assigned in Regulatory Support System 
(RSS). To access Rave via iMedidata, the site user must have an 
active CTEP-IAM account  
(check at <https://ctepcore.nci.nih.gov/iam>) and the appropriate 
Rave role (Rave CRA, Read-Only, CRA (Lab Admin, SLA or Site 
Investigator) on either the LPO or participating organization roster at 
the enrolling site. To hold the Rave CRA role or CRA Lab Admin role, 
the user must hold a minimum of an AP registration type.  To hold the 
Rave Site Investigator role, the individual must be registered as an 
NPIVR or IVR.  Associates can hold read-only roles in Rave. 
Upon initial site registration approval for the study in RSS, all persons 
with Rave roles assigned on the appropriate roster will be sent a study 
Rev. Add#2 
Rev. Add#2 
Rev. Add#3 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
25 
invitation e-mail from iMedidata. To accept the invitation, site users 
must log into the Select Login (https://login.imedidata.com/selectlogin) 
using their CTEP-IAM user name and password, and click on the 
“accept” link in the upper right-corner of the iMedidata page. Please 
note, site users will not be able to access the study in Rave until all 
required Medidata and study specific trainings are completed. 
Trainings will be in the form of electronic learnings (eLearnings), and 
can be accessed by clicking on the link in the upper right pane of the 
iMedidata screen. 
Users that have not previously activated their iMedidata/Rave account 
at the time of initial site registration approval for the study in RSS will 
also receive a separate invitation from iMedidata to activate their 
account. Account activation instructions are located on the CTSU 
website, Rave tab under the Rave resource materials (Medidata 
Account Activation and Study Invitation Acceptance). Additional 
information on iMedidata/Rave is available on the CTSU members’ 
website under the Rave tab at www.ctsu.org/RAVE/ or by contacting 
the CTSU Help Desk at 1-888-823-5923 or by e-mail at 
ctsucontact@westat.com. 
4.6.4 
Image Submission Using TRIAD 
For patients who consent to participate in the NaF PET/CT scan sub-
study. 
TRIAD is ACR’s proprietary image exchange application that will be 
used as the sole method of data transfer to the ACR Clinical 
Research Center Core Laboratory for this trial. TRIAD can be installed 
on one or several computers of choice within the institutional “firewall” 
and on the institutional network; internet access is required. The 
TRIAD application can then be configured as a DICOM destination on 
either scanner(s) and/or PACS system for direct network transfer of 
study related images into the TRIAD directory. When properly 
configured, the TRIAD software de-identifies, encrypts, and performs 
a lossless compression of the images before they are transferred to 
the ACR Imaging Core Laboratory image archive in Philadelphia. 
TRIAD Access Requirements: 
• 
Site designated staff who will submit images through TRIAD will 
need to be registered with the Cancer Therapy Evaluation 
Program (CTEP) and have a valid and active CTEP Identity and 
Access Management (IAM) account, and be registered as an AP, 
NPIVR or IVR.  Please refer to CTEP Registration Procedures of 
the protocol for instructions on how to request a CTEP-IAM 
account and complete registration in RCR. 
• 
To submit images, the site designated image submitter should be 
on the site’s affiliate rosters and be assigned the 'TRIAD site user' 
role on the CTSU roster.  Users should contact the site’s CTSU 
Administrator or Data Administrator to request assignment of the 
TRIAD site user role.  RAs are able to submit standard of care 
imaging through the same method. 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
26 
TRIAD Installations: 
When a user applies for a CTEP-IAM account with the proper user 
role, he/she will need to have the TRIAD application installed on 
his/her workstation to be able to submit images. TRIAD installation 
documentation can be found by following this link 
https://triadinstall.acr.org/triadclient/   
This process can be done in parallel to obtaining your CTEP-IAM 
account username and password and RCR registration. 
If you have any questions regarding this information, please send an 
e-mail to the TRIAD Support mailbox at TRIAD-Support@acr.org or 
call 703-390-9858. 
NOTE 
Please refrain from anonymizing the DICOM header of any 
exam prior to uploading into the TRIAD application. 
Custom DICOM editing can exclude an exam from the final 
analysis, due to the omission of technical data elements. 
These elements include, but are not limited to, the study 
date, scanner station name, scanner serial number, and 
any scan acquisition parameter. TRIAD has been uniquely 
configured to locate and scrub all PHI from the EA8153 
DICOM headers, during the image transfer to ensure the 
anonymity of our trial patients 
4.6.5 
ECOG-ACRIN Systems for Easy Entry of Patient Reported Outcomes 
(EASEE-PRO) System: 
When patients consent to participate, they will be asked to provide a 
contact email address and that address along with their registration 
information will be sent directly from the parent trial’s registration 
system to EASEE-PRO, and the patient will be automatically 
registered into EASEE-PRO for participation. To activate their account 
for self-directed web entry of surveys, the system will send an 
activation message to the contact email address that will explain how 
to activate their account for self-directed web entry of surveys. After 
their account is activated, the patient will be able to complete 
questionnaires using a secure browser interface from any web 
enabled computer, tablet, or mobile device. 
4.7 
Instructions for Patients who Do Not Start Assigned Protocol Treatment  
If a patient does not receive any assigned protocol treatment, baseline and 
follow-up data, including disease assessment, will still be collected and must be 
submitted through Medidata Rave and EASEE-PRO according to the schedule in 
the EA8153 Forms Completion Guidelines. 
Rev. Add#2 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
27 
5. 
Treatment Plan 
5.1 
Administration Schedule 
All treatment will be administered on an outpatient basis.  
Please give patients copies of the blank Patient Pill Calendars (Appendix II) 
5.1.1 
Treatment Arm A: 
5.1.1.1 
Androgen deprivation therapy with either LHRH agonist or 
antagonist or surgical castration with bilateral orchiectomy 
5.1.1.2 
Abiraterone acetate 1000 mg by mouth (PO) once daily 
continuously, 2 hours before or after meals. Abiraterone 
acetate is to be taken whole tablets with water.  Do not 
crush or chew tablets.  Abiraterone acetate is to be taken 
on an empty stomach; however, prednisone is to be 
administered with food (prednisone 5 mg BID). 
5.1.1.3 
Prednisone 5 mg PO twice daily continuously, take with 
food 
5.1.1.4 
Cabazitaxel 25 mg/m2 intravenously (IV) on day 1 every 21 
days over one hour for up to 6 cycles (1 cycle = 21 days). 
Dose of cabazitaxel will be calculated based on actual 
body weight. If the patient’s weight on the day of dosing 
differs by > 10% from the weight used to calculate the 
previous dose, the dose must be recalculated 
5.1.1.5 
G-CSF allowed per local standard practice. Examples of 
acceptable options include pegfilgrastim once, filgrastim or 
TBO-filgrastim for 5 days or equivalent 
5.1.1.6 
Premedication for cabazitaxel is required to decrease or 
prevent acute anaphylactoid reactions and to decrease the 
severely or delay the onset of late-occurring fluid retention 
problems 
To be administered IV 30 minutes before each dose of 
cabazitaxel:  
5.1.1.6.1 
Antihistamine (dexchloropheniramine 5 mg 
or diphenhydramine PO or IV 25 mg or 
equivalent antihistamine) 
5.1.1.6.2 
Corticosteroid (dexamethasone 8 mg or 
equivalent steroid) 
5.1.1.6.3 
H2 antagonist (ranitidine 50 mg or 
equivalent H2 antagonist) 
5.1.1.6.4 
Antiemetic prophylaxis is recommended and 
can be given PO or IV as needed. 
5.1.2 
Treatment Arm B: 
5.1.2.1 
Androgen deprivation therapy with either LHRH agonist or 
antagonist or surgical castration with bilateral orchiectomy 
Rev. Add#3 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
28 
5.1.2.2 
Abiraterone acetate 1000 mg PO once daily continuously, 
2 hours before or after meals. Abiraterone acetate is to be 
taken whole tablets with water.  Do not crush or chew 
tablets.  Abiraterone acetate is to be taken on an empty 
stomach; however, prednisone is to be administered with 
food (prednisone 5 mg BID). 
5.1.2.3 
Prednisone 5 mg PO twice daily continuously, take with 
food 
5.2 
Adverse Event Reporting Requirements 
All toxicity grades described in this protocol and all reportable adverse 
events on this protocol will be graded using the NCI Common Terminology 
Criteria for Adverse Events (CTCAE) version 5.0. 
All appropriate treatment areas should have access to a copy of the CTCAE 
version 5.0. A copy of the CTCAE version 5.0 can be downloaded from the 
CTEP website (http://ctep.cancer.gov). 
5.2.1 
Purpose 
Adverse event (AE) data collection and reporting, which are a 
required part of every clinical trial, are done so investigators and 
regulatory agencies can detect and analyze adverse events and risk 
situations to ensure the safety of the patients enrolled, as well as 
those who will enroll in future studies using similar agents.  
5.2.2 
Terminology 
• 
Adverse Event (AE): Any untoward medical occurrence 
associated with the use of an agent in humans, whether or not 
considered agent related. Therefore, an AE can be ANY 
unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated 
with the use of a medicinal product, whether or not considered 
related to the medicinal product.  
• 
Attribution: An assessment of the relationship between the 
adverse event and the protocol treatment, using the following 
categories. 
ATTRIBUTION 
DESCRIPTION 
Unrelated 
The AE is clearly NOT related to protocol 
treatment. 
Unlikely 
The AE is doubtfully related to protocol 
treatment. 
Possible 
The AE may be related to protocol treatment. 
Probable 
The AE is likely related to protocol treatment. 
Definite 
The AE is clearly related to protocol treatment. 
• 
CTCAE: The NCI Common Terminology Criteria for Adverse 
Events provides a descriptive terminology that is to be utilized for 
AE reporting.  A grade (severity) is provided for each AE term.  
Rev. Add#2 
Rev. Add#2 
Rev. Add#2 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
29 
• 
Expectedness: Expected events are those that have been 
previously identified as resulting from administration of the agent. 
An adverse event is considered unexpected, for expedited 
reporting purposes, when either the type of event or the severity of 
the event is NOT listed in the protocol or drug package insert. 
5.2.3 
Mechanism for Adverse Event Reporting 
Routine reporting: Adverse events are reported in a routine manner 
at scheduled times during a trial using the Medidata Rave clinical data 
management system. Please refer to Section 4 of the protocol for 
more information on how to access the Medidata Rave system and 
the EA8153 forms packet for instructions on what, where and when 
adverse events are to be reported routinely. 
Expedited reporting: In addition to routine reporting, certain adverse 
events must be reported in an expedited manner for timelier 
monitoring of patient safety and care. The remainder of this section 
provide information and instructions regarding expedited adverse 
event reporting 
5.2.4 
Expedited Adverse Event Reporting Procedure 
Adverse events requiring expedited reporting will use CTEP’s Adverse 
Event Reporting System (CTEP-AERS). CTEP’s guidelines for CTEP-
AERS can be found at http://ctep.cancer.gov.   
For this study, a CTEP-AERS report must be submitted electronically 
via the CTEP-AERS Web-based application located at 
http://ctep.cancer.gov., so that ECOG-ACRIN and all appropriate 
regulatory agencies will be notified of the event in an expeditious 
manner. 
In the rare event when Internet connectivity is disrupted a 24-hour 
notification is to be made by telephone to  
• 
the AE Team at ECOG-ACRIN (857-504-2900) 
• 
the FDA (1-800-FDA-1088)  
An electronic report MUST be submitted immediately upon re-
establishment of internet connection. 
Supporting and follow up data: Any supporting or follow up 
documentation must be uploaded to the Supplemental Data Folder in 
Medidata Rave within 48-72 hours. In addition, supporting or follow up 
documentation must be faxed to the FDA (800-332-0178) in the same 
timeframe.  
CTEP Technical Help Desk: For any technical questions or system 
problems regarding the use of the CTEP-AERS application, please 
contact the NCI Technical Help Desk at ncictephelp@ctep.nci.nih.gov 
or by phone at 1-888-283-7457. 
5.2.5 
Determination of Reporting Requirements 
Many factors determine the reporting requirements of each individual 
protocol, and which events are reportable in an expeditious manner, 
including:   
Rev. Add#2 
Rev. Add#2 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
30 
• 
the phase (0, 1, 2, or 3) of the trial  
• 
whether the patient has received an investigational or commercial 
agent or both 
• 
the seriousness of the event 
• 
the Common Terminology Criteria for Adverse Events (CTCAE) 
grade 
• 
the relationship to the study treatment (attribution) 
• 
the expectedness of the adverse event 
Using these factors, the instructions and tables in the following 
sections have been customized for protocol EA8153 and outline the 
specific expedited adverse event reporting requirements for study 
EA8153.   

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
31 
5.2.6 
Steps to determine if an event is to be reported in an expedited 
manner 
 
Identify the type and grade of the event 
using the CTCAE. 
Determine if the event is related to the 
protocol treatment (attribution). 
With this information, review the chart in 
Section 5.2.7 to determine if event is 
reportable via CTEP-AERS. 
Refer to footnote b in 
Section 5.2.7 to determine 
if the event meets the 
protocol specific reporting 
requirements for this 
study. If so, report the 
event via CTEP-AERS. 
Is the event 
reportable?
No 
Yes 
Refer to Section 5.2.7 to determine if the event meets the 
criteria as an exception to reporting on this protocol.  If it 
does not, report the event via CTEP-AERS. 
Determine the expectedness of the 
event. An unexpected event is defined as 
one where the type of severity of the 
event is not listed in the investigator’s 
brochure, package insert or protocol. 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
32 
5.2.7 
Expedited Reporting Requirements for Arms A and B on protocol 
EA8153 
Commercial Agents: Abiraterone acetate, Cabazitaxel, Prednisone 
Expedited reporting requirements for adverse events experienced by patients on arm(s) with commercial agents 
only – Arms A and B 
Attribution 
Grade 4 
Grade 5a 
ECOG-ACRIN and 
Protocol-Specific 
Requirements 
Unexpected 
Expected 
Unexpected 
Expected 
See footnote  
(b) for special 
requirements. 
Unrelated or Unlikely 
 
 
7 calendar 
days 
7 calendar 
days 
Possible,  
Probable,  
Definite 
7 calendar 
days 
 
7 calendar 
days 
7 calendar 
days 
7 Calendar Days: Indicates a full CTEP-AERS report is to be submitted within 7 calendar days of learning of the 
event. 
a 
A death occurring while on study treatment or within 30 days of the last dose of study treatment requires both 
routine and expedited reporting, regardless of causality. Attribution to treatment or other cause must be 
provided.  
NOTE: A death due to progressive disease should be reported as a Grade 5 “Disease progression” 
under the System Organ Class (SOC) “General disorder and administration site conditions”.  
Evidence that the death was a manifestation of underlying disease (e.g. radiological changes 
suggesting tumor growth or progression: clinical deterioration associated with a disease 
process) should be submitted. 
NOTE: Any death that occurs > 30 days after the last dose of treatment and is attributed possibly, 
probably, or definitely to the treatment must be reported within 7 calendar days of learning of 
the event.   
b 
Protocol-specific expedited reporting requirements: The adverse events listed below also require expedited 
reporting for this trial: 
Serious Events: 
Any event following treatment that results in persistent or significant disabilities/incapacities, 
congenital anomalies, or birth defects must be reported via CTEP-AERS within 7 calendar 
days of learning of the event. For instructions on how to specifically report these events via 
CTEP-AERS, please contact the AEMD Help Desk at aemd@tech-res.com or 301-897-7497. 
This will need to be discussed on a case-by-case basis. 
5.2.8 
Other recipients of adverse event reports and supplemental data 
Adverse events determined to be reportable via CTEP-AERS must 
also be reported by the institution, according to the local policy and 
procedures, to the Institutional Review Board responsible for oversight 
of the patient. 
5.2.9 
Second Primary Cancer Reporting Requirements 
All cases of second primary cancers, including acute myeloid 
leukemia (AML) and myelodysplastic syndrome (MDS), that occur 
following treatment on NCI-sponsored trials must be reported as 
follows: 
• 
A second malignancy is a cancer that is UNRELATED to any 
prior anti-cancer treatment (including the treatment on this 
protocol).  Second malignancies require ONLY routine reporting 
as follows: 
1. Complete a Second Primary Form in Medidata Rave within 14 
days. 
Rev. Add#2 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
33 
2. Upload a copy of the pathology report to ECOG-ACRIN via 
Medidata Rave confirming the diagnosis. 
3. If the patient has been diagnosed with AML/MDS, upload a 
copy of the cytogenetics report (if available) to ECOG-ACRIN 
via Medidata Rave. 
• 
A secondary malignancy is a cancer CAUSED BY any prior anti-
cancer treatment (including the treatment on this protocol). 
Secondary malignancies require both routine and expedited 
reporting as follows: 
1. Complete a Second Primary Form in Medidata Rave within 14 
days. 
2. Report the diagnosis on the Adverse Event Form or Late 
Adverse Event Form in the appropriate Treatment Cycle or 
Post Registration folder in Medidata Rave 
Report under a.) leukemia secondary to oncology 
chemotherapy, b.) myelodysplastic syndrome, or c.) treatment 
related secondary malignancy 
NOTE: 
When reporting attribution on the AE Form, assess 
the relationship between the secondary malignancy 
and the current protocol treatment ONLY (and NOT 
relationship to any anti-cancer treatment received 
either before or after protocol treatment). 
3. Report the diagnosis via CTEP-AERS at http://ctep.cancer.gov 
4. Upload a copy of the pathology report to ECOG-ACRIN via 
Medidata Rave and submit a copy to NCI/CTEP confirming the 
diagnosis. 
5. If the patient has been diagnosed with AML/MDS, upload a 
copy of the cytogenetics report (if available) to ECOG-ACRIN 
via Medidata Rave and submit a copy to NCI/CTEP. 
NOTE: 
The ECOG-ACRIN Second Primary Form and the CTEP-
AERS report should not be used to report recurrence or 
development of metastatic disease. 
NOTE: 
If a patient has been enrolled in more than one NCI-
sponsored study, the ECOG-ACRIN Second Primary Form 
must be submitted for the most recent trial. ECOG-ACRIN 
must be provided with a copy of the form and the 
associated pathology report and cytogenetics report (if 
available) even if ECOG-ACRIN was not the patient's most 
recent trial. 
NOTE: 
Once data regarding survival and remission status are no 
longer required by the protocol, no follow-up data should 
be submitted via CTEP-AERS or by the ECOG-ACRIN 
Second Primary Form. 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
34 
5.3 
Dose Modifications  
There will be no dose modification for androgen deprivation. Intermittent 
hormonal therapy is not allowed. 
5.3.1 
Cabazitaxel 
For cabazitaxel, no more than one dose modification to 20 mg/m2 
should be allowed for any patient. If a patient requires a second 
reduction of cabazitaxel, he will continue on abiraterone acetate 
alone. Dose adjustment are to be made according to the system 
showing the greatest degree of toxicity. Toxicities will be graded using 
the NCI Common Terminology Criteria for Adverse Events (CTCAE). 
If toxicity occurs, the appropriate treatment will be used to ameliorate 
signs and symptoms including anti-emetics for nausea and vomiting, 
anti-diarrheals for diarrhea, anti-pyretics and antihistamines for drug 
fever before toxicity grade is determined.   
Dose adjustments for toxicity should be made according to the 
guidelines below. Dose reduction is based on dose level. If a dose is 
reduced due to toxicity the dose will not be re-escalated back to 
starting level. Treatment may be delayed no more than three weeks to 
allow recovery from toxicity. If treatment must be delayed longer than 
three weeks from scheduled day of dosing, patient will be treated with 
abiraterone acetate alone. 
Dose Level 
Cabazitaxel (mg/m2) 
Level 0 (starting) 
25 mg/m2 
Level -1 
20 mg/m2 
5.3.1.1 
Dose Modification for Myelosuppression: 
Dose modifications to be made based on granulocyte 
and/or platelet count drawn prior to planned treatment (can 
be done day prior to planned dose): 
Rev. Add#2 
Rev. Add#2 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
35 
Toxicity 
Dosage Modification 
Prolonged grade ≥ 3 neutropenia 
(greater than1 week) despite 
appropriate medication including 
G-CSF 
Delay treatmenta until neutrophil count is > 1,500 
cells/mm3, then reduce dosageb of cabazitaxel to 20 
mg/m2. Use G-CSF for secondary prophylaxis. 
Febrile neutropeniac 
Delay treatmenta until improvement or resolution, and 
until neutrophil count is > 1,500 cells/mm3, then 
reduce dosageb of cabazitaxel to 20 mg/m2. Use G-
CSF for secondary prophylaxis. 
Thrombocytopenia grade > 2 
Delay treatmenta until platelet count > 75,000/mm3, 
then reduce cabazitaxel doseb to 20 mg/m2. 
a If planned day 1 dose must be delayed for three consecutive weeks, discontinue 
cabazitaxel and continue on abiraterone acetate alone. 
b If a dose reduction is made, maintain the lower dose for all subsequent cycles. 
c Grade > 3 neutropenia associated with fever (one reading of oral temperature > 
38.5oC, or three readings of oral temperature > 38oC in a 24-hour period).   
5.3.1.2 
Dose Modification for Hepatic Dysfunction: 
AST and total bilirubin will be evaluated at baseline and on 
day 1 of cycles 1-6.  
Patients who develop abnormal liver function tests for any 
reason while on the study will have the following dose 
reductions: 
Total Bilirubina 
ASTa 
Action 
> 1 to ≤ 1.5xULN 
or 
≥ 1.5xULN 
Reduce dose to 20 mg/m2; use with 
caution and monitor closely 
> 1.5xULN 
and 
any 
Discontinue cabazitaxel 
a In the absence of biliary obstruction or other contributing cause responsible for 
concurrent elevation. 
5.3.1.3 
Dose modification for Peripheral Neuropathy: 
If ≥ Grade 3, the patient will discontinue cabazitaxel. 
If Grade 2, cabazitaxel will be held and the patient should 
be retreated upon recovery to a Grade 1 toxicity with dose 
reduction of cabazitaxel to 20 mg/m2. 
If Grade 2 neurotoxicity persists for more than 3 weeks, the 
patient will discontinue cabazitaxel. 
5.3.1.4 
Dose modification for diarrhea: 
Diarrhea > grade 3 or persistent despite appropriate 
medication, fluids, and electrolyte replacement: Delay 
treatment until improves or resolves and then reduce dose 
to 20 mg/m2. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
36 
5.3.1.5 
Allergic Reactions to Cabazitaxel: 
Treatment should be discontinued for Grade 4 allergic 
reactions. There are no dose reductions for 
hypersensitivity reactions. 
Grade 4 allergic reactions are defined as a life-threatening 
event that requires pressor and/or ventilation support for 
shock associated with acidemia and impairing vital organ 
function due to tissue hypoperfusion. 
Patients with two episodes of Grade 3 Allergic reactions or 
one Grade 4 Allergic reaction are to discontinue 
cabazitaxel. 
5.3.1.6 
Delay of Therapy: 
If cabazitaxel has to be delayed for more than 3 weeks 
from planned day of dosing because of any toxicity, then 
the patient is to be treated with abiraterone acetate alone. 
5.3.1.7 
Other Toxic Effects thought to be related to Cabazitaxel: 
If clinically significant toxicities ≤ Grade 2, manage the 
subject symptomatically if possible, and retreat without 
dose reduction. 
If toxicities ≥ Grade 3 and clinically significant (not 
mentioned above), cabazitaxel should be withheld (except 
for anemia as patients can be transfused) until resolution 
to ≤ Grade 1 or baseline if baseline was greater than 
Grade 1, then reinstituted, if medically appropriate, at full 
dose or a dose reduction of one level, as clinically 
indicated. 
5.3.2 
Abiraterone Acetate 
For abiraterone acetate, no more than two dose modifications should 
be allowed for any patient. If a patient requires a third reduction of 
abiraterone acetate, treatment with abiraterone acetate will be 
discontinued. Dose adjustment are to be made according to the 
system showing the greatest degree of toxicity. Toxicities will be 
graded using the NCI Common Terminology Criteria for Adverse 
Events (CTCAE). If toxicity occurs, the appropriate treatment will be 
used to ameliorate signs and symptoms including anti-emetics for 
nausea and vomiting, anti-diarrheals for diarrhea, anti-pyretics and 
antihistamines for drug fever before toxicity grade is determined.   
Dose adjustments for toxicity should be made according to the 
guidelines that follow. Dose reduction is based on dose level. If a 
dose is reduced due to toxicity the dose will not be re-escalated to 
starting level. Exceptions apply if dose reduction to abiraterone 
acetate happened during concurrent treatment with cabazitaxel and 
after treatment with cabazitaxel is completed or discontinued. In those 
cases, re-escalation of abiraterone acetate should be discussed and 
approved by the study chair. Treatment [abiraterone] may be delayed 
no more than eight weeks to allow recovery from drug-related toxicity. 
Rev. Add#2 
Rev. Add#2 
Rev. Add#3 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
37 
If treatment must be delayed longer than eight weeks from scheduled 
day of dosing, patient will be taken off study. 
Dose Level 
Abiraterone Acetate 
Level 0 (starting) 
1000 mg once daily 
Level -1 
750 mg once daily 
Level -2 
500 mg once daily 
5.3.2.1 
Dose modification for Hepatic Dysfunction: 
AST and total bilirubin will be evaluated at baseline and 
every 21 days for the first 18 weeks and every 6 weeks 
thereafter.  
Patients who develop abnormal liver function tests for any 
reason while on abiraterone acetate will have the following 
dose reductions: 
Total Bilirubina 
ASTa 
Action 
> 3xULN 
or 
>5xULN 
Withhold treatment until return to baseline 
or AST ≤ 2.5xULN and total bilirubin ≤ 
1.5xULN, then reinitiate at 750 mg once 
daily. 
Recurrence as above at lower dose of 750 
mg once daily 
Withhold treatment until return to baseline 
or AST ≤ 2.5xULN and total bilirubin ≤ 
1.5xULN, then reinitiate at 500 mg once 
daily. 
Recurrence as above at lower dose of 500 
mg once daily 
Discontinue abiraterone acetate 
> 2xULN 
and 
> 3xULN 
Discontinue abiraterone acetate 
a In the absence of biliary obstruction or other contributing cause responsible for 
concurrent elevation. 
For patients been retreated, AST and total bilirubin should be monitored at a minimum of 
every 2 weeks for the first 3 months and monthly thereafter. 
5.3.2.2 
Dose Modification for Hypokalemia: 
At the initial observation of hypokalemia (serum potassium 
< 3.5 mmol/L or below lower limit of normal range, but ≥ 
3.0 mmol/L), oral potassium supplement should be 
initiated, as per table below. The dose of potassium 
supplement must be carefully titrated to maintain serum 
potassium from 3.5 to 5.0 mmol/L. Any subject with low 
potassium during the study or a history of hypokalemia 
from a preexisting or concurrent medical condition should 
undergo at least weekly laboratory electrolyte evaluation. 
The investigator should consider maintaining potassium ≥ 
4.0 mmol/L in these subjects. 
If any subject experiences Grade 3 hypokalemia (serum 
potassium levels < 3.0 to 2.5 mmol/L) or life-threatening 
hypokalemia with potassium levels < 2.5 mmol/L (National 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
38 
Cancer Institute Common Terminology Criteria for Adverse 
Events [NCI-CTCAE] hypokalemia Grade 4), abiraterone 
acetate treatment should be withheld and it is 
recommended that the subject be hospitalized for IV 
potassium replacement and cardiac monitoring. Re-
initiation of abiraterone acetate treatment after 
normalization of potassium levels must be discussed with 
and approved by the study chair. 
Serum Potassium 
Grade of 
Hypokalemia 
Action 
Further Action of 
Maintenance 
Low potassium or 
history of 
hypokalemia 
 
At least weekly 
laboratory 
electrolyte 
evaluation 
Titrate dose to serum 
potassium >3.5 to <5.0 
mmol/L; maintenance 
at > 4.0 mmol/L is 
recommended 
< LLN – 3.0mmol/L  
Grade 1 or 2 
Initiate oral 
potassium 
supplementation 
Titrate dose to serum 
potassium >3.5 to <5.0 
mmol/L; maintenance 
at > 4.0 mmol/L is 
recommended 
< 3.0 to 2.5 mmol/L 
Grade 3 
Withhold 
abiraterone acetate 
and initiate IV 
potassium 
supplementation 
and cardiac 
monitoring 
Call study chair before 
re-initiating abiraterone 
acetate 
< 2.5 mmol/L 
Grade 4 
Withhold 
abiraterone acetate 
and initiate IV 
potassium 
supplementation 
and cardiac 
monitoring 
Call study chair before 
re-initiating abiraterone 
acetate 
5.3.2.3 
Dose Modification for Hypertension and Edema/Fluid 
Retention: 
For patients that develop hypertension and/or edema/fluid 
retention while on treatment with abiraterone acetate, dose 
adjustment should be done as follows: 
Hypertension 
Action 
Dose of Abiraterone Acetate 
Grade 1 to 2 
Continue 1000 mg 
daily 
No change in the dose 
Grade ≥ 3 
Withhold abiraterone 
acetate and adjust/add 
medication to mitigate 
toxicity 
When grade decreases to grade < 1 or 
baseline, resume abiraterone acetate 
at the full dose 
First recurrence 
grade ≥ 3  
Withhold abiraterone 
acetate and adjust/add 
medication to mitigate 
When grade decreases to grade < 1 or 
baseline, resume abiraterone acetate 
at 750 mg daily 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
39 
toxicity 
Second recurrence 
grade > 3  
Withhold abiraterone 
acetate and adjust/add 
medication to mitigate 
toxicity 
When grade decreases to grade < 1 or 
baseline, resume abiraterone acetate 
at 500 mg daily 
Third recurrence 
grade ≥ 3 
Discontinue 
Discontinue 
5.3.2.4 
Delay of Therapy: 
If abiraterone acetate has to be delayed for more than 8 
weeks from planned day of dosing because of any 
treatment-related toxicity, then the patient will be taken off 
study. 
5.3.2.5 
Other Toxic Effects Thought to be related to Abiraterone 
Acetate: 
If toxicities ≤ Grade 2, manage the subject symptomatically 
if possible, and retreat without dose reduction. 
If toxicities ≥ Grade 3 and clinically significant (not 
mentioned above), abiraterone acetate should be withheld 
until resolution to ≤ Grade 1 or baseline if baseline was 
greater than Grade 1, then reinstituted, if medically 
appropriate, at a dose reduction of one level. No dose 
reduction below 500 mg daily will be allowed. 
5.3.3 
Prednisone 
Dose of prednisone may be reduced to 5 mg PO daily if clinically 
indicated at the discretion of the treating physician. 
5.4 
Supportive Care  
5.4.1 
All supportive measures consistent with optimal patient care will be 
given throughout the study. 
5.4.2 
Growth factor support per local standard practice (pegfilgrastim, 
filgrastim, TBO-filgrastim, lenograstim or equivalent) 
5.4.3 
Caution advised when study drugs are co-administered with other 
drugs, over-the-counter or herbal medicines that are CYP450 
isoenzymes. 
5.4.4 
Use of agents to prevent skeletal-related events (such as zoledronic 
acid or denosumab) will be allowed if initiated prior to registration or 
after Day 1 of Cycle 2. 
5.5 
Patient Reported Outcome Measures: Tobacco Use Assessment (Optional) 
Assessments will be captured directly from the participants using the EASEE-
PRO portal. When patients consent to participate, they will be asked to provide a 
contact email address and that address along with their registration information 
will be sent directly from the parent trial’s registration system to EASEE-PRO, 
and the patient will be automatically registered into EASEE-PRO for participation. 
To activate their account for self-directed web entry of surveys, the system will 
send an activation message to the contact email address that will explain how to 
Rev. Add#2 
Rev. Add#3 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
40 
activate their account for self-directed web entry of surveys. After their account is 
activated, the patient will be able to complete questionnaires using a secure 
browser interface from any web enabled computer, tablet, or mobile device. 
The Core and Extension C-TUQ items will be assessed, together with patient-
reported physical and psychological symptoms (See Table 2). Specifically, these 
items will be administered using the EASEE-PRO system described in the 
companion EA NCORP application. The advantage of our virtual electronic data 
capture system is that our proposed assessments will not be limited to, or 
dependent upon, patient trial visits.  Confidential and potentially stigmatizing 
information can be provided without requiring direct contact with the care team. 
The selected Core and Extension C-TUQ items (from categories of Basic 
Tobacco Use Information, Tobacco Use in Relation to Cancer Diagnosis and 
Treatment, Smoking Cessation/Cessation Products/Assistance Methods, Use of 
Other Products, and Second-Hand Smoke Exposure) will be assessed. The 4-
item Short Form PROMIS® for anxiety and depression, the Lung Cancer Stigma 
Scale, and six symptom items (general pain, fatigue, nausea, cough, sleep 
difficulties, shortness of breath) from FACIT (Functional Assessment of Chronic 
Illness Therapy) together with modifications of these same six questions to 
address the degree of bother associated with each symptom will be administered 
as well. Additionally, we will ask participants’ perceptions of how smoking 
improves or worsens each of the six symptom experience. All these items will be 
compiled into Survey of Tobacco Use (STU). Detailed information on various 
measures is outlined in Appendix VI. 
Contents and Corresponding Questions in Survey of Tobacco Use (STU) 
Dimension 
Source of Measures 
Baseline 
STU 
Follow-up 
STU 
Basic Tobacco Use Information 
C-TUQ 
Q1 – Q5 
Q1 – Q2 
Tobacco Use in Relation to 
Cancer Diagnosis and 
Treatment 
C-TUQ 
Q6 – Q7 
Q3 
Smoking Cessation, Cessation 
Products, and Assistance 
Methods 
C-TUQ 
Q8 – Q13 
Q4 – Q9 
Use of Other Products  
C-TUQ 
Q14 
Q10 
Second-Hand Smoke Exposure 
C-TUQ 
Q15 – Q16 
Q11 – Q12 
Psychological Symptoms 
PROMIS  
Lung Cancer Stigma 
Scale 
Q17 – Q18 
Q13 – Q14 
Physical Symptoms 
FACIT 
Q19 
Q15 
Sociodemographics 
 
Q20 – 21 
 
NOTE: 
In order to minimize ambiguity and assure that patients are oriented to 
answer appropriately, the specific phrasing of items may vary 
depending specific cancer type and treatment. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
41 
5.5.1 
Assessment Schedule 
Survey of Tobacco Use will be administered at the following time 
points: 
1. at baseline (trial enrollment) 
2. at 3 month follow-up from study registration 
3. at 6 month follow-up from study registration 
5.6 
Duration of Therapy  
Patients will receive protocol therapy unless: 
• 
Extraordinary Medical Circumstances: If at any time the constraints of this 
protocol are detrimental to the patient's health, protocol treatment should be 
discontinued. In this event submit forms according to the instructions in the 
EA8153 Forms Packet. 
• 
Patient withdraws consent. 
• 
Patient experiences unacceptable toxicity. 
• 
Non-protocol therapies are administered. 
• 
Radiographic or symptomatic progression as defined by Section 6 of the 
protocol. 
• 
The treating physician determines they are no longer benefiting from protocol 
therapy. 
5.7 
Duration of Follow-up  
For this protocol, all patients, including those who discontinue protocol therapy 
early, will be followed for response until progression, even if non-protocol therapy 
is initiated, and for survival for 5 years from the date of registration and data may 
be collected by telephone interview or chart review. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
42 
6. 
Measurement of Effect 
6.1 
Antitumor Effect – Solid Tumors  
For the purposes of this study, patients should be re-evaluated for response 
every 9 weeks for the first 18 weeks and every 12 weeks thereafter. 
Response and progression will be evaluated in this study using the international 
criteria proposed by the revised Response Evaluation Criteria in Solid Tumors 
(RECIST) guideline (version 1.1) [24]. Changes in the largest diameter 
(unidimensional measurement) of the tumor lesions and the shortest diameter in 
the case of malignant lymph nodes are used in RECIST. 
The following general principles must be followed: 
1. To assess objective response, it is necessary to estimate the overall tumor 
burden at baseline to which subsequent measurements will be compared. All 
baseline evaluations should be performed as closely as possible to the 
beginning of treatment and never more than four weeks before registration. 
2. Measurable disease is defined by the presence of at least one measurable 
lesion. 
3. All measurements should be recorded in metric notation by use of a ruler or 
calipers.  
4. The same method of assessment and the same technique must be used to 
characterize each identified lesion at baseline and during follow-up.  
6.1.1 
Definitions 
Evaluable for Objective Response 
Only those patients who have measurable disease present at 
baseline, have received at least one cycle of therapy, and have had 
their disease re-evaluated will be considered evaluable for response. 
These patients will have their response classified according to the 
definitions stated below. 
NOTE: 
Patients who exhibit objective disease progression prior to 
the end of cycle 1 will also be considered evaluable. 
Evaluable Non-Target Disease Response 
Patients who have lesions present at baseline that are evaluable but 
do not meet the definitions of measurable disease, have received at 
least one cycle of therapy, and have had their disease re-evaluated 
will be considered evaluable for non-target lesion assessment. The 
response assessment is based on the presence, absence, or 
unequivocal progression of the lesions. 
6.1.2 
Disease Parameters 
Measurable Disease 
Measurable lesions are defined as those that can be accurately 
measured in at least one dimension (longest diameter to be recorded) 
as ≥ 20 mm by chest x-ray, as ≥ 10 mm with CT or MRI scan, or ≥ 10 
mm with calipers by clinical exam. All tumor measurements must be 
recorded in millimeters. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
43 
NOTE: 
Tumor lesions that are situated in a previously irradiated 
area might or might not be considered measurable. If the 
investigator thinks it appropriate to include them, the 
conditions under which such lesions should be considered 
must be defined in the protocol. 
Malignant Lymph Nodes 
To be considered pathologically enlarged and measurable, a lymph 
node must be ≥ 15 mm in short axis when assessed by CT or MRI 
scan (CT scan slice thickness recommended to be no greater than 5 
mm). At baseline and in follow-up, only the short axis will be 
measured and followed. 
Non-measurable Disease 
All other lesions (or sites of disease), including small lesions (longest 
diameter < 10 mm or pathological lymph nodes with ≥ 10 to < 15 mm 
short axis), are considered non-measurable disease. Bone lesions, 
leptomeningeal disease, ascites, pleural/pericardial effusions, 
lymphangitis cutis/pneumonitis, inflammatory breast disease, and 
abdominal masses (not followed by CT or MRI), are considered as 
non-measurable. Non-measurable also includes lesions that are < 20 
mm by chest x-ray. 
NOTE: 
Cystic lesions that meet the criteria for radiographically 
defined simple cysts should not be considered as 
malignant lesions (neither measurable nor non-
measurable) since they are, by definition, simple cysts. 
‘Cystic lesions’ thought to represent cystic metastases can be 
considered as measurable lesions, if they meet the definition of 
measurability described above. However, if non-cystic lesions are 
present in the same patient, these are preferred for selection as target 
lesions. 
Target Lesions 
All measurable lesions up to a maximum of 2 lesions per organ and 5 
lesions in total, representative of all involved organs, should be 
identified as target lesions and recorded and measured at baseline. 
Target lesions should be selected on the basis of their size (lesions 
with the longest diameter), be representative of all involved organs, 
but in addition should be those that lend themselves to reproducible 
repeated measurements.  It may be the case that, on occasion, the 
largest lesion does not lend itself to reproducible measurement in 
which circumstance the next largest lesion which can be measured 
reproducibly should be selected.   
A sum of the diameters (longest for non-nodal lesions, short axis for 
nodal lesions) for all target lesions will be calculated and reported as 
the baseline sum diameters. If lymph nodes are to be included in the 
sum, then only the short axis is added into the sum. The baseline sum 
of the diameters will be used as reference to further characterize any 
objective tumor regression in the measurable dimension of the 
disease. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
44 
Non-target Lesions 
All other lesions (or sites of disease) including any measurable lesions 
over and above the 5 target lesions should be identified as non-target 
lesions and should also be recorded at baseline.  Measurements of 
these lesions are not required, but the presence or absence of 
unequivocal progression of each should be noted throughout follow-
up.  
6.1.3 
Symptomatic Deterioration 
Patients with a global deterioration of health status requiring 
discontinuation of treatment without objective evidence of disease 
progression at that time should be classified as having symptomatic 
deterioration. 
6.1.4 
Methods for Evaluation of Disease 
All measurements should be taken and recorded in metric notation 
using a ruler or calipers. All baseline evaluations should be performed 
as closely as possible to the beginning of treatment and never more 
than 4 weeks before registration. 
The same method of assessment and the same technique must be 
used to characterize each identified and reported lesion at baseline 
and during follow-up. Imaging-based evaluation is preferred to 
evaluation by clinical examination unless the lesion(s) being followed 
cannot be imaged but are assessable by clinical exam. 
Clinical Lesions 
Clinical lesions will only be considered measurable when they are 
superficial (e.g., skin nodules and palpable lymph nodes) and ≥ 10 
mm in diameter as assessed using calipers (e.g., skin nodules). In the 
case of skin lesions, documentation by color photography, including a 
ruler to estimate the size of the lesion, is recommended.  
Chest X-ray 
Lesions on chest x-ray are acceptable as measurable lesions when 
they are clearly defined and surrounded by aerated lung.  However, 
CT is preferable.  
Conventional CT and MRI  
This guideline has defined measurability of lesions on CT scan based 
on the assumption that CT slice thickness is 5 mm or less. If CT scans 
have slice thickness greater than 5 mm, the minimum size for a 
measurable lesion should be twice the slice thickness.  MRI is also 
acceptable in certain situations (e.g. for body scans).   
Use of MRI remains a complex issue. MRI has excellent contrast, 
spatial, and temporal resolution; however, there are many image 
acquisition variables involved in MRI which greatly impact image 
quality, lesion conspicuity, and measurement. Furthermore, the 
availability of MRI is variable globally. As with CT, if an MRI is 
performed, the technical specifications of the scanning sequences 
used should be optimized for the evaluation of the type and site of 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
45 
disease. Furthermore, as with CT, the modality used at follow-up must 
be the same as was used at baseline and the lesions should be 
measured/assessed on the same pulse sequence.  It is beyond the 
scope of the RECIST guidelines to prescribe specific MRI pulse 
sequence parameters for all scanners, body parts, and diseases.  
Ideally, the same type of scanner should be used and the image 
acquisition protocol should be followed as closely as possible to prior 
scans.  Body scans should be performed with breath-hold scanning 
techniques, if possible. 
PET-CT 
At present, the low dose or attenuation correction CT portion of a 
combined PET-CT is not always of optimal diagnostic CT quality for 
use with RECIST measurements. However, if the site can document 
that the CT performed as part of a PET-CT is of identical diagnostic 
quality to a diagnostic CT (with IV and oral contrast), then the CT 
portion of the PET-CT can be used for RECIST measurements and 
can be used interchangeably with conventional CT in accurately 
measuring cancer lesions over time. Note, however, that the PET 
portion of the CT introduces additional data which may bias an 
investigator if it is not routinely or serially performed. 
Ultrasound 
Ultrasound is not useful in assessment of lesion size and should not 
be used as a method of measurement. Ultrasound examinations 
cannot be reproduced in their entirety for independent review at a 
later date and, because they are operator dependent, it cannot be 
guaranteed that the same technique and measurements will be taken 
from one assessment to the next.  If new lesions are identified by 
ultrasound in the course of the study, confirmation by CT or MRI is 
advised. If there is concern about radiation exposure at CT, MRI may 
be used instead of CT in selected instances. 
FDG-PET 
While FDG-PET response assessments need additional study, it is 
sometimes reasonable to incorporate the use of FDG-PET scanning 
to complement CT scanning in assessment of progression 
(particularly possible 'new' disease). New lesions on the basis of 
FDG-PET imaging can be identified according to the following 
algorithm:  
a. Negative FDG-PET at baseline, with a positive FDG-PET at 
follow-up is a sign of PD based on a new lesion. 
b. No FDG-PET at baseline and a positive FDG-PET at follow-up:  If 
the positive FDG-PET at follow-up corresponds to a new site of 
disease confirmed by CT, this is PD. If the positive FDG-PET at 
follow-up is not confirmed as a new site of disease on CT, 
additional follow-up CT scans are needed to determine if there is 
truly progression occurring at that site (if so, the date of PD will be 
the date of the initial abnormal FDG-PET scan). If the positive 
FDG-PET at follow-up corresponds to a pre-existing site of 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
46 
disease on CT that is not progressing on the basis of the anatomic 
images, this is not PD. 
c. FDG-PET may be used to upgrade a response to a CR in a 
manner similar to a biopsy in cases where a residual radiographic 
abnormality is thought to represent fibrosis or scarring.  The use of 
FDG-PET in this circumstance should be prospectively described 
in the protocol and supported by disease-specific medical 
literature for the indication.  However, it must be acknowledged 
that both approaches may lead to false positive CR due to 
limitations of FDG-PET and biopsy resolution/sensitivity. 
NOTE: 
A ‘positive’ FDG-PET scan lesion means one which is FDG 
avid with an uptake greater than twice that of the 
surrounding tissue on the attenuation corrected image. 
6.1.5 
Methods for Evaluation of Bone Disease 
Bone disease will be evaluated using radionuclide bone scan. 
6.1.6 
Evaluation of Radionuclide Bone Scans 
Interpretation of serial changes in a radionuclide bone scan is well 
recognized to be highly subjective. Thus, the primary outcome will be 
whether the bone scan is stable or improved, vs. worse or 
progression. Changes in intensity will not be used as an outcome 
measure. The 2+2 rule will be applied for interpretation of bone scans: 
Stable or Improved: Include 1) resolution of skeletal lesions, 2) 
absence of new skeletal lesions or 3) the appearance of new skeletal 
lesions on the first post-treatment scan with absence of at least 2 
additional skeletal lesions in the next (confirmatory) scan performed 6 
or more weeks later. Changes in intensity of a preexisting lesion will 
be considered stable disease unless associated with other signs of 
progression. 
Progression (Non-Response): For patients with 2 or more new lesions 
in the first post-treatment scan, the appearance of at least 2 additional 
new lesions on a subsequent scan must be documented to qualify for 
disease progression. For patients with no new lesions in the first post-
treatment scan, the appearance of at least 2 or more new lesions 
must be documented to qualify for disease progression. In all cases, 
these lesions must be confirmed by a subsequent (confirmatory) scan. 
The day of progression is the day that the first 2 lesions following the 
first post-treatment scan were noted. An increase in the size or 
intensity of known skeletal lesions will not be considered progression. 
6.1.7 
Response Criteria 
6.1.7.1 
Evaluation of Target Lesions 
Complete Response (CR) 
Disappearance of all target lesions. Any pathological lymph 
nodes (whether target or non-target) must have reduction 
in short axis to < 10 mm. 
Rev. Add#2 
Rev. Add#2 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
47 
Partial Response (PR) 
At least a 30% decrease in the sum of the diameters of 
target lesions, taking as reference the baseline sum 
diameters 
Progressive Disease (PD) 
At least a 20% increase in the sum of the diameters of 
target lesions, taking as reference the smallest sum on 
study (this includes the baseline sum if that is the smallest 
on study). In addition to the relative increase of 20%, the 
sum must also demonstrate an absolute increase of at 
least 5 mm. 
NOTE: 
The appearance of one or more new lesions is 
also considered progression, See Section 
6.1.7.3. 
Stable Disease (SD) 
Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest 
sum diameters while on study. (Note: a change of 20% or 
more that does not increase the sum of the diameters by 5 
mm or more is coded as stable disease) 
To be assigned a status of stable disease, measurements 
must have met the stable disease criteria at least once 
after study registration at a minimum interval of 12 weeks. 
6.1.7.2 
Evaluation of Non-Target Lesions 
Complete Response (CR) 
Disappearance of all non-target lesions. All lymph nodes 
must be non-pathological in size (< 10 mm short axis). 
Non-CR/Non-PD 
Persistence of one or more non-target lesion(s) and/or the 
maintenance of tumor marker levels above the normal 
limits. To be assigned a status of stable disease, 
measurements must have met the stable disease criteria at 
least once after study registration at a minimum interval of 
at least 12 weeks.  
Progressive Disease (PD) 
Appearance of one or more new lesions and/or 
unequivocal progression of existing non-target lesions (see 
Section 6.1.7.3). Unequivocal progression should not 
normally trump target lesion status. It must be 
representative of overall disease status change, not a 
single lesion increase. 
When the patient also has measurable disease, there must 
be an overall level of substantial worsening in non-target 
disease such that, even in the presence of SD or PR in 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
48 
target disease, the overall tumor burden has increased 
sufficiently to merit discontinuation of therapy.  A modest 
“increase” in the size of one or more non-target lesions is 
usually not sufficient to qualify for unequivocal progression 
status. The designation of overall progression solely on the 
basis of change in non-target disease in the face of SD or 
PR of target disease will therefore be extremely rare. 
When the patient only has non-measurable disease, the 
increase in overall disease burden should be comparable 
in magnitude to the increase that would be required to 
declare PD for measurable disease: i.e., an increase in 
tumor burden from “trace” to “large”, an increase in nodal 
disease from “localized” to “widespread”, or an increase 
sufficient to require a change in therapy. 
Although a clear progression of “non-target” lesions only is 
exceptional, the opinion of the treating physician should 
prevail in such circumstances, and the progression status 
should be confirmed at a later time by the review panel (or 
Principal Investigator). 
6.1.7.3 
Evaluation of New Lesions 
The appearance of new lesions constitutes Progressive 
Disease (PD). For bone lesions please refer to Section 
6.1.6. 
A growing lymph node that did not meet the criteria for 
reporting as a measurable or non-measurable lymph node 
at baseline should only be reported as a new lesion (and 
therefore progressive disease) if it:  
a) increases in size to ≥ 15 mm in the short axis, or  
b) there is new pathological confirmation that it is disease 
(regardless of size). 
c) new effusion or ascites that appears during treatment 
should only be reported as a new lesion (and therefore 
progressive disease) if it has cytological confirmation of 
malignancy. 
6.1.7.4 
Evaluation of Best Overall Response 
The best overall response is the best response recorded 
from the start of the treatment until disease 
progression/recurrence or non-protocol therapy, taking as 
reference for progressive disease the smallest 
measurements recorded since registration. The table 
below provides overall responses for all possible 
combinations of tumor responses in target and non-target 
lesions, with or without new lesions. 
To be assigned a status of complete or partial response, 
changes in tumor measurements must be confirmed by 
Rev. Add#2 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
49 
repeat assessments performed no less than four weeks 
after the criteria for response are first met. 
To be assigned a status of stable disease, measurements 
must have met the stable disease criteria at least once 
after study registration at a minimum interval of at least 8 
weeks.  
Overall Response for all Possible Combinations of 
Tumor Response 
NOTE: 
For this protocol, time to radiographic 
progression is being evaluated and the 
following table will apply. 
Target 
Lesions 
Non-Target  
Lesions 
New Lesions* 
Bone Lesions 
Best Overall 
Response 
Remarks  
CR 
CR 
No 
Stable or 
Improved 
CR 
 
CR 
Non-CR/Non-PD*** 
No 
Stable or 
Improved 
PR 
 
CR 
Not evaluated 
No 
Stable or 
Improved 
PR 
PR 
Non-PD***/not 
evaluated 
No 
Stable or 
Improved 
PR 
SD 
Non-PD***/not 
evaluated 
No 
Stable or 
Improved 
SD 
Documented 
at least 
once ≥ 12 
wks. from 
study 
registration 
PD 
Any 
Yes or No 
Any 
PD 
No prior SD, 
PR or CR 
Any 
PD** 
Yes or No 
Any 
PD*** 
Any 
Any 
Yes 
Any 
PD 
Any 
Any 
Yes or No 
PD 
PD 
 
* 
See RECIST 1.1 manuscript for further details on what is evidence of a new lesion. 
** In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as 
disease progression. 
*** PD in non-target lesions should not normally trump target lesion status. It must be representative of 
overall disease status change, not a single lesion increase. Please refer to the Evaluation of Non-
Target Lesions – Progressive Disease section for further explanation. 
NOTE: Patients with a global deterioration of health status requiring discontinuation of treatment without 
objective evidence of disease progression at that time should be reported as “symptomatic 
deterioration.” Every effort should be made to document the objective progression even after 
discontinuation of treatment. 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
50 
6.2 
Serological Response 
6.2.1 
Response according to PSA levels 
PSA levels will be assessed at the time of randomization, then every 3 
weeks for the first 18 weeks and then every 6 weeks thereafter. 
Patient’s PSA will be assigned a response according to the following 
criteria: 
Complete Serological Response (CR): PSA level less than 0.02 
ng/mL measured for 2 consecutive measurements at least 3 weeks 
apart.  
Serological Partial Response (PR): Decline of PSA value, 
referenced to the PSA at time of study entry level, by greater than or 
equal to 50% for 2 consecutive measurements at least 3 weeks apart. 
Serological Progression (PD): Increase in PSA to more than 25% of 
nadir and > 2 ng/mL above the nadir, taking as reference the lowest 
recorded PSA since starting treatment on the study. Two consecutive 
increases must be documented with each measurement obtained at 
least 3 weeks apart (i.e., a confirmed rising trend). On occasions, 
there may be an intermediate fluctuant value. This will not restart the 
evaluation period so long as the intermediate value was not below the 
previous nadir. The date of the first recorded increase that meets the 
criteria above (not defeated by a subsequent drop in PSA level to 
create a new nadir) will be deemed the date of progression. Early 
rises in PSA (before 12 weeks from initiation of therapy) will be 
ignored in determining disease progression. 
6.3 
Endpoint Definitions 
6.3.1 
Progression-Free Survival (PFS) 
PFS is defined as time from randomization to radiographic 
progression, symptomatic deterioration or death, whichever occurs 
first. Patients who are alive without documented progression or 
symptomatic deterioration will be censored at the date of last disease 
assessment. 
6.3.2 
Time to PSA progression 
Time to PSA progression is defined as time from randomization to 
PSA progression as defined in 6.2.1. 
6.3.3 
Radiographic response  
Radiographic response, either CR or PR, is defined by RECIST 1.1 as 
per Section 6.1. 
6.3.4 
Overall survival (OS) 
OS is defined as time from randomization to death or date last known 
alive. 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
51 
7. 
Study Parameters 
7.1 
Therapeutic Parameters  
1. 
Prestudy scans and x-rays used to assess all measurable or non-measurable sites of disease must be done ≤ 4 
weeks prior to randomization. 
2. Prestudy laboratories outlined in Sections 3 and 7.1 must be done and resulted ≤ 4 weeks prior to randomization. 
 
Baseline 
Daily (on 
treatment) 
Day 1, Cycle 
1a 
Day 1, 
Cycle 2-6a 
Follow-up: 
Every 6 
weeks  
(+/- 3 days)b 
End of 
treatmentc 
Long-Term 
Follow-upd 
Abiraterone acetate (Daily, Both Arms) 
 
X 
X 
X 
X 
 
 
Prednisone (Daily, Both Arms) 
 
X 
X 
X 
X 
 
 
Cabazitaxel (Arm A only) 
 
 
X 
X 
 
 
 
Demographics, Medical History, Height 
X 
 
 
 
 
 
 
Concurrent meds 
X 
 
X 
X 
X 
 
 
Physical exam, interval history, vital signs, 
weight, ECOG performance status, 
survival status. 
X 
 
X 
X 
X 
X 
 
CBC with differential, platelets  
X 
 
Xj 
Xj 
Xj 
X 
 
Serum chemistrye 
X 
 
Xj 
Xj 
Xj 
X 
 
PSA 
X 
 
Xj 
Xj 
Xj 
X 
Xd 
EKG (as clinically indicated) 
X 
 
 
 
 
 
 
Adverse event evaluation 
 
 
X 
X 
X 
X 
Xd 
Tumor measurements (CT scan of the 
chest/abdomen/pelvis and bone scan) 
X 
 
Radiologic tumor measurements on 
treatment are to be performed  every 9 
weeks (+/- 7 days) for the first 18 weeks 
and every 12 weeks (+/- 7 days) thereafter 
from the patient’s treatment start date.  
Documentation (radiologic) must be 
provided for patients removed from study 
for progressive disease 
Xc 
Xd 
(OPTIONAL) NaF PET/CTf 
Xg 
 
 
Xh 
 
 
 
(OPTIONAL) Tobacco Use Assessment PROsi 
See Section 5.6 
Rev. Add#2 
Rev. Add#3 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
52 
a. One cycles equals 21 days (+/- 3 days) 
b. Starting 21 days (+/-3 days) from the last dose of cabazitaxel (21 days +/- 3 days after cycle 6 day 1) 
c. Off-study evaluation ≤ 30 days after last treatment on study and prior to starting new therapy. Scans do not need to be repeated at the end of the 
study visit if progression was noted. 
d. The following will be required during Long Term Follow Up 
• 
Patients that discontinue protocol treatment due to radiographic progression:  Survival status updates only* 
• 
Patients that discontinue protocol treatment due to symptomatic deterioration: CT chest/abdomen/pelvis, bone scan**, & survival 
status updates* 
• 
Patients that discontinue protocol treatment before radiographic progression or symptomatic deterioration, but have serologically 
progressed: CT chest/abdomen/pelvis, bone scan**, & survival status updates* 
NOTE: Patients that have serologically progressed are not required to discontinue protocol treatment. 
Patients that discontinue protocol treatment for reasons other than serological progression, radiographic progression, or symptomatic 
deterioration: PSA, CT chest/abdomen/pelvis, bone scan**, & survival status updates* 
*Survival data will be collected for all patients either by phone or during office visit every 3 month is patient is < 2 years from study entry, every 6 
months if patient is 2-3 years from study entry and then annually for up to year 5. 
**Patients that require scans in follow-up: every effort should be made to have a radiographic assessment with CT scan and bone scan done 
every 3 months until radiographic or clinical progression.  Patients do not have to repeat scans after they have disease progression. 
NOTE: Please refer to Section 6 for definitions of progression 
NOTE: Serious Adverse Events (SAEs) that meet the requirements in Section 5.2 should continue to be reported via CTEP-AERS for all 
patients in long-term follow up, even if they have progressed 
e. Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, chloride, creatinine, glucose, LDH, phosphorus, potassium, total 
protein, SGOT [AST], SGPT [ALT], sodium. Testosterone due at baseline only. 
f. Please see Section 4.6.4 for image submission instructions to submit NaF PET/CT scan images for patients consented to the NaF PET sub-
study. 
g. Within 7 days prior to starting treatment. 
h. Day 85 +/- 7 days. 
i. Tobacco use assessment PROs will be collected using EASEE-PRO for consenting patients. 
j. Can be obtained within 72 hours prior to visit. 
 
Rev. Add#3 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
53 
7.2 
Biological Sample Submissions  
Specimens are to be submitted as outlined in Section 1. 
All specimens must be entered and tracked via the online ECOG-ACRIN Sample 
Tracking System (STS). 
Biological 
Materials1 
Prior to 
Start of 
Treatment 
Day 85  
Time of Disease 
Progression 
Submit to: 
From patients who answer “Yes” to “I agree to have my samples collected and I agree 
that my samples and related information may be used for the laboratory studies.” 
Peripheral Blood 
(two 8.5mL ACD 
yellow top tubes) 
X2 
X3 
X4 
Johns Hopkins 
University 
From patients who answer “Yes” to “I agree to provide additional blood for research.” 
Peripheral Blood 
(two 10mL 
Streck Cell-Free 
DNA tubes) 
X2 
X3 
X4 
CBPF 
1. Kits are being provided for the collection and shipment of the blood specimens. 
See Appendix IV for instructions. Kit orders will on average be delivered within 
three (3) business days from the time the order is placed.  
2. Within seven (7) days prior to starting treatment. 
3. +/- seven (7) days. 
4. Within 30 days from last treatment on study and prior to starting new therapy 
 
Rev. Add#3 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
54 
8. 
Drug Formulation and Procurement 
Abiraterone acetate and prednisone are commercially available and guideline endorsed 
treatment options for patients with prostate cancer. Drug will be obtained from 
commercial supply. 
Genzyme is supplying Cabazitaxel free of charge and will be distributed by Patwell 
Pharmaceutical Solutions. Under no circumstances can commercially supplied 
cabazitaxel be used or substituted for the patient specific cabazitaxel supplied by 
Genzyme. 
8.1 
Abiraterone acetate  
8.1.1 
Other Names  
Zytiga 
8.1.2 
Classification  
Androgen biosynthesis inhibitor 
8.1.3 
Mode of Action  
Selectively and irreversibly inhibits CYP17(17 alpha-
hydroxylase/C17,20-lyase ), an enzyme required for androgen 
biosynthesis which is expressed in testicular, adrenal, and prostatic 
tumor tissues. Inhibits the formation of testosterone precursors 
dehydroepiandrosterone (DHEA) and androstenendione. 
8.1.4 
Storage and Stability  
Store at room temperature Store at room temperature (20° to 25°C 
[68° to 77°F]), with excursions permitted between 15° and 30°C (59° 
and 86°F). 
8.1.5 
Dose Specifics  
Starting dose: 1000mg PO daily - continuously 
8.1.6 
Preparation 
N/A 
8.1.7 
Route of Administration  
Oral. 
8.1.8 
Incompatibilities  
N/A 
8.1.9 
Availability  
Commercial. 
8.1.10 
Side Effects  
≥ 10% of patients may experience fatigue, joint swelling or discomfort, 
edema, hot flush, diarrhea, vomiting, cough, hypertension, dyspnea, 
urinary tract infection and contusion. 
Most common Labs abnormalities >20% include anemia, elevated 
alkaline phosphatase, hypertriglyceridemia, lymphopenia, 
Rev. Add#3 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
55 
hypercholesteremia, hyperglycemia, elevated AST/ALT, 
hypophosphatemia, and hypokalemia. 
8.1.11 
Nursing/Patient Implications  
Hazardous agent. Use appropriate precautions for handling, 
administration and disposal. 
8.1.12 
References  
Lexicomp 
8.2 
Cabaxitaxel 
Please refer to the package insert or institutional preparation guidelines for 
additional information. 
8.2.1 
Other Names  
Jevtana 
8.2.2 
Classification  
Taxoids, antineoplastic agent 
8.2.3 
Mode of Action  
Cabazitaxel is a taxane derivative that is microtubule inhibitor; it binds 
to tubulin promoting assembly into microtubules and inhibiting 
disassembly which stabilizes microtubules, This inhibits microtubule 
depolymerization and cell division, arresting the cell cycle and 
inhibiting tumor proliferation. Unlike other taxanes, cabazitxel has a 
poor affinity for MDR proteins, therefore conferring activity in resistant 
tumors. 
8.2.4 
Storage and Stability  
Store at room temperature Store intact vials at 25°C (77°F); 
excursions permitted between 15°C and 30°C (59°F and 86°F). Do 
not refrigerate. 
8.2.5 
Dose Specifics  
Starting dose: 25 mg/m2 
8.2.6 
Preparation 
Do not prepare or administer in PVC containing infusion containers or 
polyurethane infusion sets.  Both Cabazitaxel and diluent vials contain 
overfill. 
• 
Slowly inject the entire contents of the provided diluent vial into 
the cabazitaxel 60mg/1.5ml via, directing the diluent down the vial 
wall. Mix gently by inverting the vial for at least 45 seconds. Do 
NOT shake.  Allow vial to sit so that foan dissipates and solution 
appears homogeneous. This results in a concentration of 
10mg/ml. Use within 30 mins of reconstituting vial. 
• 
Withdraw calculated dose and add to a 250ml D5W or NS non 
PVC infusion container for a final concentration of 0.1 to 
0.26mg/ml. (total doses >65mg will require larger infusion 
volumes). Gently invert container to mix. Do not use if 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
56 
crystals/precipitate appear. Infusion should be completed within 8 
hours if stored at room temperature. For infusion solution stored 
under refrigeration, the infusion should be completed within 24 
hrs. 
8.2.7 
Route of Administration  
Intravenous. 
8.2.8 
Incompatibilities  
N/A 
8.2.9 
Availability  
Cabazitaxel is provided free of charge by Genzyme and will be 
distributed by Patwell Pharmaceutical Solutions. Cabazitaxel is 
supplied in a single-use 60mg/1.5mL vial. 
Cabazitaxel should only be ordered for patients randomized to 
Arm A. 
Initial Drug Orders for Each Patient 
Following randomization to Arm A, a supply of Cabazitazel may be 
ordered. Investigators must email a completed EA8153 Cabazitaxel 
Study Drug Request Form to the ECOG-ACRIN Drug Team at 
900.drugorder@jimmy.harvard.edu or send by fax to (617) 589-0919. 
A copy of the EA8153 Cabazitaxel Study Drug Request Form is 
available for download from the CTSU website (www.ctsu.org). No 
starter supplies are available for this protocol. 
Please refer to Appendix V for the EA8153 Cabazitaxel Study Drug 
Request Form download instructions. 
Cabazitaxel will be shipped to a responsible person (e.g., a 
pharmacist) at the investigator’s institution. Sites should order 
enough vials to complete 3 cycles of treatment (1 vial/cycle = 3 
vials needed). 
Institutions should allow up to 4 business days to receive drug 
onsite. Patwell Pharmaceutical Solutions will ship and arrange 
drug deliveries to sites on business days only; there will be no 
weekend or holiday delivery of drugs. 
IMPORTANT REORDER INSTRUCTIONS 
Once it is determined that the patient will continue treatment, please 
reorder 3 cycles of treatment (1 vial/cycle = 3 vials needed) of 
study drug immediately byemailing a completed EA8153 Cabazitaxel 
Study Drug Request Form to the ECOG-ACRIN Drug Team at 
900.drugorder@jimmy.harvard.edu or send by fax to (617) 589-0919 
Institutions should keep in mind the number of vials used per cycle, 
and that Cabazitaxel is provided in in single-use 60mg/1.5mL vials. 
Institutions should allow up to 4 business days to receive drug onsite. 
Patwell Pharmaceutical Solutions will ship and arrange drug deliveries 
to sites on business days only; there will be no weekend or holiday 
delivery of drugs. 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
57 
Drug Destruction and Return 
At the completion of each patient’s treatment at your institution, all 
unused drugs, partially used, or empty containers must be destroyed 
at the site according to the institution’s policy for drug destruction. 
Please maintain appropriate records of the disposal, including dates 
and quantities. 
Please refer to Appendix V for ‘EA8153 Investigational Product 
Destruction Record’ download instructions. 
Drug Inventory Records 
The investigator, or a responsible party designated by the 
investigator, must maintain a careful record of the receipt, dispensing 
and final disposition of all agents using the appropriate NCI 
Investigational Agent (Drug) Accountability Record (DARF) available 
on the CTEP forms page.  Store and maintain separate NCI 
Investigational Agent Accountability Records for each agent, strength, 
formulation and ordering investigator on this protocol. 
8.2.10 
Side Effects  
≥ 10% (all grades) of patients experienced neutropenia, anemia, 
leukopenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, 
constipation, asthenia, abdominal pain, hematuria, back pain, 
anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, 
arthralgia, and alopecia. 
Warning: severe hypersensitivity reactions can occur and may include 
generalized rash/erythema, hypotension and bronchospasms. All 
patients should receive premedication. 
8.2.11 
Nursing/Patient Implications  
Hazardous agent. Use appropriate precautions for handling, 
administration and disposal. Infuse over 1 hour using a 0.22 micron 
in- line filter. Allow infusion bag to reach room temperature prior to 
infusing. Premedicate with an antihistamine, a corticosteroid, and an 
H2 antagonist at least 30 minutes prior to infusion. 
8.2.12 
References  
Lexicomp 
8.3 
Prednisone  
8.3.1 
Other Names  
Deltasone, Orasone, Medicorten, Panasol-S, Liquid-Pred, others. 
8.3.2 
Classification  
Adrenal corticosteroid 
8.3.3 
Mode of Action  
Prednisone is a potent synthetic glucocorticoid that affects almost 
every body system. It has anti-inflammatory, immunosuppressant, and 
minimal mineralocorticoid activity, and antineoplastic properties. As an 
antineoplastic agent, prednisone may bind to specific proteins 
Rev. Add4 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
58 
(receptors) within the cell forming a steroid-receptor complex. Binding 
of the receptor-steroid complex with nuclear chromatin alters mRNA 
and protein synthesis within the cell. 
8.3.4 
Storage and Stability  
The drug is stored at room temperature in a dry place. 
8.3.5 
Dose Specifics  
Starting dose: 5mg PO BID - continuously 
8.3.6 
Preparation 
N/A 
8.3.7 
Route of Administration  
Oral. 
8.3.8 
Incompatibilities  
N/A 
8.3.9 
Availability  
Commercial. 
8.3.10 
Side Effects  
1. Gastrointestinal: Nausea, vomiting, anorexia; increased appetite 
and weight gain; peptic ulceration. 
2. Dermatologic: Rash; skin atrophy; facial hair growth, acne, facial 
erythema; ecchymoses. 
3. Genitourinary: Menstrual changes (amenorrhea, menstrual 
irregularities). 
4. Neurologic: Insomnia; muscle weakness; euphoria, psychosis, 
depression; headache, vertigo, seizures. 
5. Cardiovascular: Fluid retention and edema; hypertension. 
6. Ocular: Cataracts; increased intraocular pressure; exophthalmos. 
7. Metabolic: Hyperglycemia; decreased glucose tolerance; 
aggravation or precipitation of diabetes mellitus; adrenal 
suppression; Cushingoid features; hypokalemia. 
8. Hematologic: Leukocytosis. 
9. Other: Osteoporosis (and resulting back pain); serious infections 
including herpes zoster, varicella zoster, fungal infections, 
pneumocystis carinii, tuberculosis; muscle wasting; delayed 
wound healing; suppression of reactions to skin tests. 
8.3.11 
Nursing/Patient Implications  
1. Instruct patients to take prednisone after meals. Should not be 
taken too close to bedtime to avoid insomnia. A mild sedative may 
be required. 
2. GI symptoms should be treated symptomatically. 
3. Monitor blood glucose levels. 
4. Educate patient concerning potential mood swings. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
59 
5. Gradual tapering of doses after long-term use should be 
employed. 
8.3.12 
References  
Lexicomp 
Pickup ME: Clinical pharmacokinetics of prednisone and 
prednisolone. Clin Pharmacokinet 4:111-128, 1979. 
The Boston Collaborative Drug Surveillance Program: Acute reactions 
to prednisone in relation to dosage. J Clin Pharmacol 13:694-698, 
1972. 
Ling MHM, Perry PJ, Tsuang MT: Side effects of corticosteroid 
therapy: Psychiatric aspects. Arch Gen Psychiatry 38:471-477, 1981. 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
60 
9. 
Statistical Considerations 
9.1 
Primary Objective 
The primary objective of this randomized phase II study is to determine whether 
the addition of 6 cycles of cabazitaxel to abiraterone acetate (Arm A) improved 
progression-free survival (PFS) compared to abiraterone acetate alone (Arm B) 
in patients with castration-resistant prostate cancer (CRPC) that have previously 
received docetaxel and androgen deprivation therapy (ADT) for hormone-
sensitive prostate cancer (HSPC). PFS is defined as time from randomization to 
radiographic progression, symptomatic deterioration or death, whichever occurs 
first. Patients who are alive without documented progression or symptomatic 
deterioration will be censored at the date of last disease assessment. 
Prior studies have shown a median PFS of 5.6 months among metastatic CRPC 
patients treated with abiaterone acetate after receiving docetaxel for CRPC and a 
median PFS of 16.5 months among chemotherapy-naïve patients treated with 
abiraterone acetate for metastatic CRPC. Therefore, we assume a median PFS 
of 12 months among the study population who are treated with abiraterone 
acetate alone and consider a 50% improvement, to a median PFS of 18 months, 
to be of interest for the combination arm. 
9.2 
Study Design 
CRPC patients who have previously received docetaxel and ADT for HSPC will 
be randomized with a 1:1 randomization scheme to arms A and B. Stratification 
factors include ECOG performance status (0 vs. 1-2), time from initiation of ADT 
to the development of CRPC (≤ 12 months vs. > 12 months) and presence of 
visceral metastases (Yes vs. No). 
We aim to accrue 105 patients per arm for a total of 210 patients in this study. 
E3805 accrued 16 patients per month in the last two years of accrual. Currently 
docetaxel is given to metastatic prostate cancer patients with high-volume 
disease, and about 65% of patients on E3805 had high-volume disease. As the 
proposed study is a phase II trial, we expect to accrue 6 patients per month. The 
total accrual will be completed in about 35 months. All patients will be followed 
for an additional 18.5 months. With the proposed design, the study has 90% 
power to distinguish an 18-month median PFS in the combination arm from a 12-
month median PFS in the abiaterone alone arm using a one-sided stratified 
logrank test with 10% type I error. Full information will exist when 166 of the 210 
patients in the two arms have progressed or died. The primary comparison will 
be an intention to treat analysis of all randomized patients. Although patients will 
be stratified by ECOG performance status, time to CRPC development and 
presence of visceral metastases, no subgroup analyses based on these 
characteristics are planned. 
There will be two interim analyses conducted at 33% (55 PFS events; projected 
to occur at 22.5 months after study activation) and 67% (111 PFS events; 
projected to occur after the end of the accrual period at 35 months) information. 
The overall type I error will be controlled using an O’Brien-Fleming boundary 
function. Repeated confidence interval will be used for futility monitoring. If the 
repeated two-sided 80% confidence interval on the hazard ratio does not contain 
the target alternative hazard ratio (arm A vs. arm B) of 0.67, the Data Safety 
Monitoring Committee may consider stopping the trial early. If the interim logrank 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
61 
test is positive, the study can be reported early before the projected end of the 
follow-up period. Under the accrual and failure rate assumptions above, the 
following table gives the operating characteristics for PFS interim and final 
analyses. Because of delays in initiation of accrual and delays in data submission 
and processing, it is likely that the actual analysis times will be 6-12 months later. 
Repeated 
Analysis 
Real Time 
(Months) 
Information 
Time 
Number of 
Failures 
under 
Alternative 
Hypothesis 
Nominal 
Significance 
Upper 
Boundary 
Lower 
Boundary 
for Futility 
Monitoring 
Number 
of 
Patients 
1 
22.5 
0.33 
55 
0.0043 
2.6269 
-1.1162 
135 
2 
35 
0.67 
111 
0.0430 
1.7171 
0.4055 
210 
Final 
53.5 
1.00 
166 
0.0868 
1.3607 
1.3607 
210 
9.3 
Statistical Consideration for Secondary Objectives 
The secondary endpoints of this study include percent change in PSA from 
baseline to week 12 of treatment, maximum decline in PSA while on treatment, 
time to PSA progression, radiographic response, overall survival (OS) and 
toxicity of the combination treatment. 
PSA level will be assessed at baseline, every 3 weeks for the first 18 weeks and 
every 6 weeks thereafter. The percent change in PSA from baseline to 12 weeks 
and the maximum change in PSA from baseline while on treatment will be 
compared between the two arms using Wilcoxon rank sum test. With 105 
patients per arm, there will be 90% power to detect an effect size of 0.37, 
assuming one-sided type I error of 0.1. PSA progression will be assessed based 
on the definition in Section 6.2.1. Time to PSA progression is defined as the time 
from randomization to PSA progression. Patients without documented PSA 
progression will be censored at the last disease assessment. The distribution of 
time to PSA progression will be estimated using the Kaplan-Meier method. 
Stratified log rank test will be used to compare time to PSA progression between 
the two arms.   
OS, defined as time from randomization to time of death or date last known alive, 
will be estimated for each arm using the Kaplan-Meier method and the stratified 
logrank test will be used to compare this endpoint across treatments. At the final 
analysis, the study will have 73% power to detect a hazard ratio of 0.67 with one-
sided type I error of 0.1, assuming median OS of 36 months in the abiraterone 
acetate alone arm. 
Another secondary endpoint of interest is radiographic response assessed per 
RECIST 1.1. Fisher's exact test will be used to compare the radiographic 
response rates between the two arms. Patients with radiographic response 
unknown or unevaluable will be considered as non-responders in this analysis. 
Safety and tolerability of the study drugs be assessed by the CTCAE. All patients 
who receive treatment, regardless of eligibility, will be evaluated for toxicity and 
the percent of patients with various toxicities will be tabulated. The 90% 
confidence interval for the true probability of observing a toxicity of Grade 4 or 
higher in a given arm will be no wider than 17%. The probability of observing one 
or more toxicities among all 210 patients with a true rate of 1% is 88%. Interim 
analyses of toxicity are performed twice yearly for all ECOG-ACRIN studies. 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
62 
Reports of these analyses are sent to the ECOG-ACRIN Principal Investigator or 
Senior Investigator at the participating institutions. Expedited reporting of certain 
adverse events is required, as described in Section 5.2. 
9.4 
Statistical Considerations for Exploratory Objectives 
AR-V7 status will be assessed at baseline, at week 12 and at the time of disease 
progression. The proportion of AR-V7 positive patients at each time point will be 
summarized for each arm. The proportion of patients with AR-V7 status change 
at week 12 and disease progression will also be reported. To evaluate whether 
the addition of cabazitaxel would change the AR-V7 status among patients who 
are AR-V7 positive at baseline, Fisher's exact test will be used to compare the 
proportion of patients who become AR-V7 negative at follow-up assessments 
between the two arms among patients who are AR-V7 positive at baseline. 
Assuming 80% of patients will have sufficient samples for the AR-V7 analysis at 
both baseline and follow-up time points and 90% of samples will be delivered 
within 24 hours, there will be 75 analyzable patients in each arm for the analysis 
of AR-V7 status change. We anticipate about 15% of patients to be positive for 
AR-V7 at baseline and about 50% of these patients to convert to AR-V7 negative 
after receiving cabazitaxel. Assuming 11 (75*15%) patients with positive AR-V7 
at baseline in each arm, the study has about 71% power to detect a difference in 
AR-V7 conversion rate of 50% vs. 10% between Arms A and B among AR-V7 
positive patients using Fisher’s exact test with one-sided type I error of 0.15. 
Similar analysis will be performed to compare the proportion of patients who 
become AR-V7 positive at disease progression among those who are AR-V7 
negative at baseline. Assuming 64 (75*85%) patients with negative AR-V7 at 
baseline in each arm, the study has about 80% power to detect a difference in 
AR-V7 conversion rate of 15% vs. 30% between Arms A and B among AR-V7 
negative patients using Fisher’s exact test with one-sided type I error of 0.15. In 
addition, Cox regression will be used to evaluate the associations between 
baseline AR-V7 status and PFS as well as OS and its interaction with treatment. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
63 
9.5 
Gender and Ethnicity 
Based on previous data from E3805 the anticipated accrual in subgroups defined 
by gender and race is: 
Ethnic Category 
 
Gender 
Females 
Males 
Total 
Hispanic or Latino 
0 
12 
12 
Not Hispanic or Latino 
0 
198 
198 
Ethnic Category: Total of all subjects 
0 
210 
210 
 
Racial Category 
American Indian or Alaskan Native 
0 
0 
0 
Asian 
0 
3 
3 
Black or African American 
0 
23 
23 
Native Hawaiian or other Pacific Islander 
0 
0 
0 
White 
0 
184 
184 
Racial Category: Total of all subjects 
0 
210 
210 
The accrual targets in individual cells are not large enough for definitive 
subgroup analyses.  Therefore, overall accrual to the study will not be 
extended to meet individual subgroup accrual targets. 
9.6 
Study Monitoring 
This study will be monitored by the ECOG-ACRIN Data Safety Monitoring 
Committee (DSMC). The DSMC meets twice each year. For each meeting, all 
monitored studies are reviewed for safety and progress toward completion. When 
appropriate, the DSMC will also review interim analyses of outcome data. Copies 
of the toxicity reports prepared for the DSMC meetings are included in the study 
reports prepared for the ECOG-ACRIN group meeting (except that for double 
blind studies, the DSMC may review unblinded toxicity data, while only pooled or 
blinded data will be made public). These group meeting reports are made 
available to the local investigators, who may provide them to their IRBs. Only the 
study statistician and the DSMC members will have access to interim analyses of 
outcome data. Prior to completion of this study, any use of outcome data will 
require approval of the DSMC. Any DSMC recommendations for changes to this 
study will be circulated to the local investigators in the form of addenda to this 
protocol document. A complete copy of the ECOG-ACRIN DSMC Policy can be 
obtained from the ECOG-ACRIN Operations Office – Boston. 
9.7 
Tobacco Use Assessment 
Detailed statistical considerations are outlined in Appendix VI 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
64 
10. 
Imaging Research Study 
All NaF PET/CT images are to be submitted via TRIAD as outlined in Section 4.6.4 
10.1 
NaF PET/CT Imaging  
The overall goal of this study is to examine whether the addition of cabazitaxel to 
abiraterone acetate can improve the overall response as well as the percentage 
of responding lesions compared to abiraterone acetate alone in support of our 
hypothesis. We expect a total of 50 eligible patients will be accrued in the sub-
study. All participants will receive two imaging studies according to study 
protocol: pre-treatment NaF PET/CT at baseline and a mid-treatment NaF 
PET/CT at week 12. Eligible participants who have consented to this study will be 
actively involved in the trial and will be followed for treatment outcomes per 
protocol. NaF PET/CT image analysis will be performed at AIQ Solutions, Inc., 
using the FDA 510(K) cleared software 
10.1.1 
Imaging Schedule 
Pre-treatment NaF PET/CT Imaging: this imaging study should be 
completed prior to treatment start.  
Mid-Treatment NaF PET/CT Imaging: this imaging study should be 
completed during week 12 (day 85 +/- 7 days) of the study treatment.  
10.1.2 
18F-NaF Administered Dose 
Place an intravenous catheter (IV), 18 or 20 gauge is preferred, in a 
vein of the participant’s arm; inject  18F-fluoride (NaF) (0.14 mCi/kg of 
radiotracer up to a maximum of 10 mCi) into the IV in the participant’s 
arm. A saline flush should follow the 18F-NaF injection. Perform a 
static whole body PET scan from mid-thigh to head after 60 minutes 
and CT attenuation correction scan; 
NOTE: 
Imaging will take approximately 30 to 60 minutes, 
depending on the device and procedure for attenuation 
correction. 
10.1.3 
Imaging Quality Assurance (QA)/Quality Control (QC) Procedure 
Participant must be scanned on PET/CT scanners that have been 
qualified by the ACR Imaging Core Laboratory per the protocol-
specific instructions made available to participating sites. 
Qualification Utility for the Imaging Core Laboratory (QUIC) is the 
web-based tool for managing the qualification process and 
communicating with the core lab staff. The QUIC User Guide will be 
made available to participating sites. 
Refer to the instructions about uploading images and completing the 
required application forms. 
A hybrid PET/CT scanner is mandatory. The ability to calculate 
standardized uptake values (SUVs) is also mandatory. All sequential 
imaging sessions should be performed on the same PET/CT scanner, 
whenever possible. Any deviations should be reported to ECOG-
ACRIN. QA/QC procedures will include review of DICOM files against 
study protocols. The PET/CT scanner must be kept calibrated in 
Rev. Add#2 
Rev. Add#3 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
65 
accordance with the manufacturer’s recommendations. The scanner 
should routinely be assessed for quantitative integrity and stability by 
being tested using various imaging protocols on a standard phantom. 
For SUV measurements, this assessment should include a 
comparison against a dose calibrator to ensure accuracy; that is, a 
comparison of the absolute activity measured versus the measured 
activity injected, should be performed. 
A daily QC check must be performed at the beginning of the day, 
including PET/CT scanner and dose calibrator, in accordance with the 
manufacturer recommendations. If any of the QC results are outside 
of the manufacturer’s guidelines, the study must be rescheduled and 
the problem rectified before scanning any patients. 
10.1.4 
Imaging Aims and Statistics 
There are three imaging aims in this correlative study. 
10.1.4.1 
To assess if the changes in total tumor burden from 
baseline to week 12 as assessed with NaF PET/CT will 
differ between two arms. 
For the imaging Aim 1, we assume the mean percentage 
of SUVtotal decrease was 30% in the abiraterone acetate 
alone arm [25, 27] and 60% (i.e., doubled) in the 
combination of cabazitaxel and abiraterone acetate arm, 
respectively, while the percentage of decrease is defined 
as (post SUVtotal – pre SUVtotal)/pre SUVtotal * 100%. 
The standard deviation was assumed to be 40% for both 
groups. Under the type I error 0.10 (two-sided), the sample 
size of 50 (25 in each arm) can achieve 83% power to 
detect the difference between two arms. Two-sample t-test 
assuming equal variance in PASS 14 was used for the 
computation. 
10.1.4.2 
To correlate total tumor burden at baseline as assessed 
with NaF PET/CT with the PFS. 
For Aim 2, the total tumor burden is calculated as the sum 
of SUVtotal from all voxels and all lesions. The standard 
deviation at the baseline is assumed 6000 based on the 
data from the previous studies [26].  The association with 
PFS will be analyzed through Cox regression. Assuming 
the R-square of total tumor burden with other covariates is 
0.1, the sample size of 50 can achieve 1.0 power to detect 
a hazard ratio of 1.1 with 1 unit change of total tumor 
burden, when the event rate is anticipated 0.50.  The 
power remains 1.0 when the event rate is 0.30 or 0.70. A 
two-sided Cox regression with 0.05 significance level in 
PASS 14 was used for the computation. The other 
covariates in the Cox regression include age, performance 
status, clinical stage and treatment arm. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
66 
10.1.4.3 
To correlate heterogeneity of response from baseline to 
week 12 as assessed with NaF PET/CT with the PFS. 
For the imaging Aim 3, the heterogeneity of response is 
defined as the standard deviation of SUVmean from all 
lesions. The standard deviation of difference from baseline 
to week 12 is assumed 3.5 based on the data from the 
previous studies [26]. The association with PFS will be 
analyzed through Cox regression. Assuming the R-square 
of the heterogeneity of response with other covariates is 
0.1, the sample size of 50 can achieve 0.86 power to 
detect a hazard ratio of 1.2 with 1 unite change, when the 
event rate is anticipated 0.50. The power is 0.65 or 0.95 
when the event rate is 0.30 or 0.70, respectively. A two-
sided Cox regression with 0.05 significance level in PASS 
14 was used for the computation. The other covariates in 
the Cox regression include age, performance status, 
clinical stage and treatment arm. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
67 
11. 
Submission of Biospecimens for Research 
Peripheral blood is to be submitted from consenting patients for defined laboratory 
research studies and/or undefined research. 
It is required that all specimens submitted on this trial be entered and tracked using the 
ECOG-ACRIN Sample Tracking System (see Section 11.4). An STS shipping manifest 
form is to be included with every submission. 
All specimens must be labeled clearly with the ECOG-ACRIN protocol number 
(EA8153), ECOG-ACRIN patient sequence number, patient’s initials, date and time of 
specimen collection, time point and specimen type. 
11.1 
Sample Collection and Submission Schedule 
Kits for the collection and shipment of the peripheral blood specimens are 
ordered on-line from Cenetron Central Laboratories. Instructions are provided in 
Appendix IV. Questions regarding kits can be directed to 
projectmanagement@cenetron.com or call the Cenetron Clinical Trials Group at 
(512) 439-2000. Kits must be ordered after the patient has been randomized to 
the trial and will generally arrive within three (3) business days from when the 
order was placed. 
Specimens are to be submitted as follows: 
• 
Peripheral blood specimens are to be submitted per patient consent as 
outlined in Sections 11.2 and 11.3. Blood specimens are to be collected at 
the following time points for each tube type: 
• 
Prior to Start of Treatment 
• 
Week 12 
• 
Time of Disease Progression 
11.2 
Submissions to the ECOG-ACRIN Central Biorepository and Pathology Facility 
(CBPF) 
If you have any questions concerning specimen collection and shipment, please 
contact the ECOG-ACRIN CBPF at (844) 744-2420. 
11.2.1 
Peripheral Blood Submissions 
Submit from patients who answer “Yes” to “I agree to provide 
additional blood for research.” 
Peripheral blood is to be collected as outlined in Section 11.1 
11.2.1.1 
Specimen Preparation Guidelines 
Streck Tubes  
• 
Draw two (2) 10mL Streck Cell-Free DNA BCT tubes of 
blood at each time point. 
• 
Ensure that at least 10mL of blood is drawn into each 
tube. Avoid low volume to minimize agitation during 
shipping. 
• 
Invert the tubes gently 180 degrees and back 8-10 
times. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
68 
• 
Maintain blood at room temperature (6°C to 37°C) until 
shipping. Do Not place tubes in refrigerator. 
11.2.2 
Shipping Procedures 
Peripheral blood specimens are to be shipped at ambient temperature 
Monday-Thursday via overnight courier. 
Friday shipments are ill advised, similarly shipping before 
holidays is often problematic. The laboratory is closed Saturday, 
Sunday, and holidays.  
Ship using the CBPF’s FedEx account using the FedEx on-line ship 
manager. 
Ship to: 
ECOG-ACRIN Central Biorepository and Pathology Facility 
MD Anderson Cancer Center 
Department of Pathology, Unit 085 
Tissue Qualification Laboratory for ECOG-ACRIN, Room G1.3598 
1515 Holcombe Boulevard 
Houston, TX 77030 
Phone: Toll Free (844) 744-2420 (713-745-4440 Local or 
International Sites) 
Fax: (713) 563-6506 
Email: eacbpf@mdanderson.org 
Access to the FedEx shipping account for shipments to the ECOG-
ACRIN CBPF at MD Anderson Cancer Center can only be obtained 
by logging onto fedex.com with an account issued by the ECOG-
ACRIN CBPF. For security reasons, the account number will no 
longer be given out in protocols, over the phone, or via email. If your 
site needs to have an account created, please contact the ECOG-
ACRIN CBPF by email at eacbpf@mdanderson.org 
An STS shipping manifest form must be generated and shipped with 
all specimen submissions.  
11.3 
Submissions to Johns Hopkins University 
If you have any questions concerning specimen collection and shipment, please 
contact Jun Luo at (443) 287-5625. 
11.3.1 
Peripheral Blood Submissions 
Submit from patients who answer “Yes” to “I agree to have my 
samples collected and I agree that my samples and related 
information may be used for the laboratory studies.” 
Peripheral blood is to be collected as outlined in Section 11.1 
11.3.1.1 
Specimen Preparation Guidelines 
ACD Yellow Top Tubes  
• 
Draw two (2) 8.5mL Solution A Vacutainer tubes of 
blood at each time point. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
69 
• 
Ensure that at least 8.5mL of blood is drawn into each 
tube. Avoid low volume to minimize agitation during 
shipping. 
• 
Invert the tubes gently 180 degrees and back 3-4 
times. 
• 
Store blood refrigerated at 4°C to 8°C until shipping. 
Do not put on ice. Do not leave blood refrigerated 
overnight. Ship blood the day of collection. 
11.3.2 
Shipping Procedures 
Peripheral blood specimens are to be shipped the same day they are 
drawn Monday-Thursday via overnight courier. 
Friday shipments are ill advised, similarly shipping before 
holidays is often problematic. The laboratory is closed Saturday, 
Sunday, and holidays.  
Activate the NanoCool shipper and place the tubes wrapped in bubble 
wrap (or inserted into plastic tube holders) snugly in the shipping box.  
Ship using the CBPF’s FedEx account using the FedEx on-line ship 
manager. 
Notify Dr. Luo’s laboratory of the tracking number on the day of 
shipment by emailing jluo1@jhmi.edu 
Ship to: 
Jun Luo, Ph.D. 
411 Marburg, Johns Hopkins Hospital 
6100 N. Wolfe Street 
Baltimore, MD 21287 
Tel: (443) 287-5626 
Email: jluo1@jhmi.edu 
An STS shipping manifest form must be generated and shipped with 
all specimen submissions.  
11.4 
ECOG-ACRIN Sample Tracking System  
It is required that all specimens submitted on this trial be entered and tracked 
using the ECOG-ACRIN Sample Tracking System (STS). The software will allow 
the use of either 1) an ECOG-ACRIN user-name and password previously 
assigned (for those already using STS), or 2) a CTSU username and password.   
When you are ready to log the collection and/or shipment of the specimens 
required for this study, please access the Sample Tracking System software by 
clicking https://webapps.ecog.org/Tst  
Important: Please note that the STS software creates pop-up windows, so you 
will need to enable pop-ups within your web browser while using the software. A 
user manual and interactive demo are available by clicking this link: 
http://www.ecog.org/general/stsinfo.html 
Please take a moment to familiarize yourself with the software prior to using the 
system. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
70 
An STS generated shipping manifest form should be shipped with all specimen 
submissions. 
Please direct your questions or comments pertaining to the STS to ecog-
acrin.tst@jimmy.harvard.edu 
Study Specific Notes 
Generic Specimen Submission Form (#2981v3) will be required only if STS is 
unavailable at time of specimen submission. Notify the laboratory of the shipment 
by faxing a copy of the completed form to the laboratory. 
Retroactively enter all specimen collection and shipping information when STS is 
available. 
11.5 
Use of Specimens in Research 
Specimens from patients who consented to allow their specimens to be used for 
future undefined ECOG-ACRIN approved research studies will be retained in an 
ECOG-ACRIN designated central repository. 
For this trial, specimens will be retained at the ECOG-ACRIN Central 
Biorepository and Pathology Facility.  
Specimens submitted will be processed to maximize their utility for current and 
future research projects. DNA, RNA, serum, and plasma (if appropriate) will be 
isolated from the submitted peripheral blood specimens. 
If future use is denied or withdrawn by the patient, the specimens will be 
removed from consideration for use in any future research study. Specimens will 
be destroyed per guidelines of the respective repository. 
11.6 
Sample Inventory Submission Guidelines  
Inventories of all specimens submitted from institutions will be tracked via the 
ECOG-ACRIN STS and receipt and usability verified by the receiving laboratory.  
Inventories of specimens forwarded and utilized for approved laboratory research 
studies will be submitted by the investigating laboratories to the ECOG-ACRIN 
Operations Office - Boston on a monthly basis in an electronic format defined by 
the ECOG-ACRIN Operations Office - Boston. 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
71 
12. 
Laboratory Research Studies 
Results of these studies are for the purposes of the trial only and will not be returned to 
the site or reported to the patient. 
12.1 
Association of Androgen-Receptor Splice Variant 7 Messenger RNA (AR-V7) 
Presence in Circulating Tumor Cells and Response to Treatment and Outcome 
It has been shown that the detection of androgen-receptor splice variant 7 
messenger RNA (AR-V7) in circulating tumor cells from patients with CRPC is 
associated with resistance to abiraterone acetate and enzalutamide, whereas it is 
not associated with resistance to taxanes [18, 19]. In an initial study, a total of 31 
patients treated with enzalutamide and 31 patients treated with abiraterone 
acetate were prospectively evaluated for the presence of AR-V7, which was 
detected in 39% and 19%, respectively [18]. Among patients receiving 
abiraterone acetate, AR-V7 positivity was associated with lower PSA response 
rate (0% vs. 68%; p=0.004), and shorter PSA PFS (1.3 months vs. not reached; 
p<0.001), clinical or radiographic PFS (2.3 months vs. not reached; p<0.001) and 
OS (10.6 months vs. not reached; p=0.006). However, in patients treated with 
taxanes, it appears that the presence of AR-V7 does not confer resistance to 
treatment [19]. From the 37 taxane-treated patients, 17 (46%) were tested 
positive for AR-V7. Both AR-V7 positive and negative patients had similar 
responses to therapies, assessed both by PSA and radiographically. A pooled 
analysis of patients from both studies showed that outcomes were superior with 
taxanes compared to enzalutamide or abiraterone acetate in AR-V7-positive men 
(PSA responses 41% vs. 0%; p<0.001), PSA PFS (HR 0.19; 95% CI 0.07-0.52; 
p=0.001) and radiographic PFS (HR 0.21; 95% CI 0.007-0.59; p=0.003). 
Our aim is to prospectively examine: a) whether patients positive for AR-V7 at 
baseline have a longer radiographic or clinical PFS to the combination of 
cabazitaxel and abiraterone acetate vs. abiraterone acetate alone; b) whether the 
addition of cabazitaxel can change the AR-V7 status of patients who are positive 
at study registration; and c) whether the addition of cabazitaxel to abiraterone 
acetate has any impact on future development of AR-V7 positivity at the time of 
disease progression. PFS is again defined as time from randomization to 
radiographic or clinical progression or death without progression. AR-V7 status at 
baseline, at 12 weeks into treatment and at the time of disease progression will 
be analyzed and the proportion of AR-V7 positive patients will be summarized for 
each arm. The proportion of patients with AR-V7 status change at 12 weeks and 
disease progression will also be reported. In addition, Cox regression will be 
used to evaluate the associations between AR-V7 status and PFS as well as OS 
and its interaction with treatment. 
12.2 
Lab Data Transfer Guidelines 
The data collected on the above mentioned laboratory research studies will be 
submitted electronically using a secure data transfer to the ECOG-ACRIN 
Operations Office – Boston by the investigating laboratories on a quarterly basis 
or per joint agreement between ECOG-ACRIN and the investigator. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
72 
13. 
Electronic Data Capture 
Please refer to the EA8153 Forms Completion Guidelines for the forms submission 
schedule. Data collection will be performed exclusively in Medidata Rave and EASEE-
PRO (for tobacco use assessment). 
This study will be monitored by the Clinical Data Update System (CDUS) version 3.0. 
Cumulative CDUS data will be submitted quarterly from the ECOG-ACRIN Operations 
Office – Boston to CTEP by electronic means. 
14. 
Patient Consent and Peer Judgment 
Current FDA, NCI, state, federal and institutional regulations concerning informed 
consent will be followed. 
15. 
References 
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 
2016;66(1):7-30 
2. Pound CR, Partin AW, Eisenberger MA, Chan DW, Pearson JD, Walsh PC. Natural 
history of progression after PSA elevation following radical prostatectomy. JAMA. 
1999;281(17):1591-1597 
3. Trock BJ, Han M, Freedland SJ, et al. Prostate cancer-specific survival following 
salvage radiotherapy vs observation in men with biochemical recurrence after radical 
prostatectomy. JAMA. 2008;299(23):2760-2769. 
4. Huggins C et al. Studies on prostatic cancer: II. The effect of castration on advanced 
carcinoma of the prostate gland. Arch Surg. 1941; 43:2009. 
5. Sharifi N, Gulley JL, Dahut WL. Androgen deprivation therapy for prostate cancer. 
JAMA. 2005;294(2):238-244. 
6. Cheng HH, Lin DW, Yu EY. Advanced clinical states in prostate cancer. Urol Clin 
North Am. 2012;39(4):561-571. 
7. Suzman DL, Antonarakis ES. Castration-resistant prostate cancer: latest evidence 
and therapeutic implications. Ther Adv Med Oncol. 2014;6(4):167-179. 
8. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic 
Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746. 
9. Eigl BJ, Eggener SE, Baybik J, et al. Timing is everything: preclinical evidence 
supporting simultaneous rather than sequential chemohormonal therapy for prostate 
cancer. Clin Cancer Res. 2005;11(13):4905-4911. 
10. Zhu ML, Horbinski CM, Garzotto M, et al. Tubulin-targeting chemotherapy impairs 
androgen receptor activity in prostate cancer. Cancer Res. 2010;70(20):7992-8002. 
11. James ND, Sydes MR, Clarke NW, et al. Addition of docetaxel, zoledronic acid, or 
both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): 
survival results from an adaptive, multiarm, multistage, platform randomised 
controlled trial. Lancet. 2016;19(387)10024:1163-77. 
12. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in 
metastatic prostate cancer. N Engl J Med. 2011;364(21):1995-2005. 
13. Fizazi K, Scher HI, Molina A, et al. Abiraterone acetate for treatment of metastatic 
castration-resistant prostate cancer: final overall survival analysis of the COU-AA-
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
73 
301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 
2012;13(10):983-992. 
14. Ryan CJ, Smith MR, de Bono JS, et al. Abiraterone in metastatic prostate cancer 
without previous chemotherapy. N Engl J Med. 2013;368(2):138-148. 
15. Ryan CJ, Smith MR, Fizazi K, et al. Abiraterone acetate plus prednisone versus 
placebo plus prednisone in chemotherapy-naive men with metastatic castration-
resistant prostate cancer (COU-AA-302): final overall survival analysis of a 
randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 
2015;16(2):152-160. 
16. de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or 
mitoxantrone for metastatic castration-resistant prostate cancer progressing after 
docetaxel treatment: a randomised open-label trial. Lancet. 2010;376(9747):1147-
1154. 
17. Mateo J et al. Phase 1/2 trial of cabazitaxel with abiraterone acetate in patients with 
metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel 
and abiraterone acetate: Phase 2 results. J Clin Oncol 33, 2015 (suppl 7; abstr 268). 
http://meetinglibrary.asco.org/content/141013-159. 
18. Antonarakis ES, Lu C, Wang H, et al. AR-V7 and resistance to enzalutamide and 
abiraterone in prostate cancer. N Engl J Med. 2014;371(11):1028-1038. 
19. Antonarakis ES, Lu C, Luber B, et al. Androgen Receptor Splice Variant 7 and 
Efficacy of Taxane Chemotherapy in Patients With Metastatic Castration-Resistant 
Prostate Cancer. JAMA Oncol. 2015;1(5):582-591. 
20. Liu G et al. Quantitative total bone imaging in patients with metastatic castration-
resistant prostate cancer using NaF PET/CT. J Clin Oncol 33, 2015 (suppl; abstr 
e16016). http://meetinglibrary.asco.org/content/145159-156. 
21. Yip S, Perk T, Jeraj R. Development and evaluation of an articulated registration 
algorithm for human skeleton registration. Phys Med Biol. 2014;59(6):1485-1499. 
22. Yip S, Jeraj R. Use of articulated registration for response assessment of individual 
metastatic bone lesions. Phys Med Biol. 2014;59(6):1501-1514. 
23. Scher HI, Morris MJ, Stadler WM, et al. Trial Design and Objectives for Castration-
Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer 
Clinical Trials Working Group 3. J Clin Oncol. 2016;34(12):1402-1418. 
24. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in 
solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 
2009;45(2):228-247. 
25. Harmon SA, Perk T, Lin C, et al. Quantitative Assessment of Early 18F-NaF PET/CT 
Response to Treatment in Men with Metastatic Prostate Cancer to Bone, J Clin 
Oncol (submitted) 
26. Lin C, Bradshaw T, Perk T, et al. Repeatability of Quantitative 18F-NaF PET: A 
Multicenter Study. J Nucl Med. 2016;57(12):1872-1879. 
27. Jeraj R, et al. Quantitative Assessment of Early [18F] Sodium Fluoride Positron 
Emission Tomography/Computed Tomography Response to Treatment in Men With 
Metastatic Prostate Cancer to Bone. J Clin Oncol 2017;35(24): 2829-2837. 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
74 
Cabazitaxel with Abiraterone versus Abiraterone alone Randomized Trial for Extensive 
Disease following Docetaxel: the CHAARTED2 Trial 
 
Appendix I 
 
Patient Thank You Letter 
We ask that the physician use the template contained in this appendix to prepare a letter 
thanking the patient for enrolling in this trial. The template is intended as a guide and can 
be downloaded from the web site at http://www.ecog.org. As this is a personal letter, 
physicians may elect to further tailor the text to their situation. 
This small gesture is a part of a broader program being undertaken by ECOG-ACRIN 
and the NCI to increase awareness of the importance of clinical trials and improve 
accrual and follow-through. We appreciate your help in this effort. 
 ________________________________________________________________________  
 
[PATIENT NAME] 
[DATE] 
[PATIENT ADDRESS] 
 
 
Dear [PATIENT SALUTATION], 
 
Thank you for agreeing to take part in this important research study. Many questions 
remain unanswered in cancer. With the participation of people like you in clinical trials, 
we hope to improve treatment and quality of life for those with your type of cancer. 
We believe you will receive high quality, complete care. I and my research staff will 
maintain very close contact with you. This will allow me to provide you with the best care 
while learning as much as possible to help you and other patients. 
On behalf of [INSTITUTION] and ECOG-ACRIN, we thank you again and look forward to 
helping you. 
 
 
Sincerely, 
 
 
 
 
[PHYSICIAN NAME] 
 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
75 
Cabazitaxel with Abiraterone versus Abiraterone alone Randomized Trial for Extensive 
Disease following Docetaxel: the CHAARTED2 Trial 
 
Appendix II 
 
Patient Pill Calendar 
Pill Calendar Directions 
1. Take your scheduled dose of each pill. 
2. If you forget, the missed pills will not be taken later. 
3. Please bring the empty bottle or any leftover tablets and your  
pill calendar to your next clinic visit. 
 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
76 
Patient Pill Calendar: Abiraterone acetate 
This is a calendar on which you are to record the time and number of tablets you take each day.  
You should take your scheduled dose of each pill. Note the times and the number of tablets 
that you take each day. If you develop any side effects, please record them and anything you 
would like to tell the doctor in the space provided. Bring any unused tablets and your completed 
pill calendar to your doctor’s visits. 
NOTE: 
Abiraterone acetate is taken once daily, continuously, on an empty stomach 2 hours 
before or after meals. Abiraterone acetate is to be taken whole tablets with water. Do 
not crush or chew tablets. 
NOTE: 
As prednisone must be taken with food, you can not take abiraterone acetate and 
prednisone together. 
Patient ID: 
Agent Name: Abiraterone acetate 
DAY 
Date 
 
 
Month  Day   Year 
Time pills 
taken 
 
 
AM       PM 
Number of 
pills taken 
 
 
 
Use the space below to make notes 
about things you would like to tell the 
doctor (including unusual symptoms 
you experience, other medicine you 
have taken and anything else you 
think would be of interest.) 
1 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
 
7 
 
 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
 
9 
 
 
 
 
 
 
 
 
10 
 
 
 
 
 
 
 
 
11 
 
 
 
 
 
 
 
 
12 
 
 
 
 
 
 
 
 
13 
 
 
 
 
 
 
 
 
14 
 
 
 
 
 
 
 
 
15 
 
 
 
 
 
 
 
 
16 
 
 
 
 
 
 
 
 
17 
 
 
 
 
 
 
 
 
18 
 
 
 
 
 
 
 
 
19 
 
 
 
 
 
 
 
 
20 
 
 
 
 
 
 
 
 
21 
 
 
 
 
 
 
 
 
22 
 
 
 
 
 
 
 
 
Rev. Add#3 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
77 
Patient ID: 
Agent Name: Abiraterone acetate 
DAY 
Date 
 
 
Month  Day   Year 
Time pills 
taken 
 
 
AM       PM 
Number of 
pills taken 
 
 
 
Use the space below to make notes 
about things you would like to tell the 
doctor (including unusual symptoms 
you experience, other medicine you 
have taken and anything else you 
think would be of interest.) 
23 
 
 
 
 
 
 
 
 
24 
 
 
 
 
 
 
 
 
25 
 
 
 
 
 
 
 
 
26 
 
 
 
 
 
 
 
 
27 
 
 
 
 
 
 
 
 
28 
 
 
 
 
 
 
 
 
Investigator Signature: ______________________ Investigator Date: ____________________ 
Rev. Add#3 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
78 
Patient Pill Calendar: Prednisone 
This is a calendar on which you are to record the time and number of tablets you take each day.  
You should take your scheduled dose of each pill. Note the times and the number of tablets 
that you take each day. If you develop any side effects, please record them and anything you 
would like to tell the doctor in the space provided. Bring any unused tablets and your completed 
pill calendar to your doctor’s visits. 
NOTE: 
Prednisone is taken twice daily, continuously, with food. 
NOTE: 
As abiraterone acetate must be taken on an empty stomach, you cannot take 
abiraterone acetate and prednisone together. 
Patient ID: 
Agent Name: Prednisone 
DAY 
Date 
 
 
Month  Day   Year 
Time pills 
taken 
 
 
AM       PM 
Number of 
pills taken 
 
 
AM      PM 
Use the space below to make notes 
about things you would like to tell the 
doctor (including unusual symptoms 
you experience, other medicine you 
have taken and anything else you 
think would be of interest.) 
1 
 
 
 
 
 
 
 
 
2 
 
 
 
 
 
 
 
 
3 
 
 
 
 
 
 
 
 
4 
 
 
 
 
 
 
 
 
5 
 
 
 
 
 
 
 
 
6 
 
 
 
 
 
 
 
 
7 
 
 
 
 
 
 
 
 
8 
 
 
 
 
 
 
 
 
9 
 
 
 
 
 
 
 
 
10 
 
 
 
 
 
 
 
 
11 
 
 
 
 
 
 
 
 
12 
 
 
 
 
 
 
 
 
13 
 
 
 
 
 
 
 
 
14 
 
 
 
 
 
 
 
 
15 
 
 
 
 
 
 
 
 
16 
 
 
 
 
 
 
 
 
17 
 
 
 
 
 
 
 
 
18 
 
 
 
 
 
 
 
 
19 
 
 
 
 
 
 
 
 
20 
 
 
 
 
 
 
 
 
21 
 
 
 
 
 
 
 
 
22 
 
 
 
 
 
 
 
 
23 
 
 
 
 
 
 
 
 
24 
 
 
 
 
 
 
 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
79 
Patient ID: 
Agent Name: Prednisone 
DAY 
Date 
 
 
Month  Day   Year 
Time pills 
taken 
 
 
AM       PM 
Number of 
pills taken 
 
 
AM      PM 
Use the space below to make notes 
about things you would like to tell the 
doctor (including unusual symptoms 
you experience, other medicine you 
have taken and anything else you 
think would be of interest.) 
25 
 
 
 
 
 
 
 
 
26 
 
 
 
 
 
 
 
 
27 
 
 
 
 
 
 
 
 
28 
 
 
 
 
 
 
 
 
Investigator Signature: ______________________ Investigator Date: ____________________ 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
80 
Cabazitaxel with Abiraterone versus Abiraterone alone Randomized Trial for Extensive 
Disease following Docetaxel: the CHAARTED2 Trial 
 
Appendix III 
 
ECOG Performance Status 
PS 0 
Fully active, able to carry on all pre-disease performance without restriction 
PS 1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature e.g., light house work, office work. 
PS 2 
Ambulatory and capable of all self-care but unable to carry out any work 
activities. Up and about more than 50% of waking hours. 
PS 3 
Capable of only limited self-care, confined to bed or chair more than 50% of 
waking hours. 
PS 4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or 
chair. 
 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
81 
Cabazitaxel with Abiraterone versus Abiraterone alone Randomized Trial for Extensive 
Disease following Docetaxel: the CHAARTED2 Trial 
 
Appendix IV 
 
EA8153 Collection and Shipping Kit Order Instructions 
Specimen Collection/Shipping Kits are being provided by CENETRON CENTRAL 
LABORATORIES and are to be ordered ONLINE. 
Starter kits are not available. Kit requests are to be made AFTER patient randomization. 
Questions regarding kits can be directed to projectmanagement@cenetron.com or call 
the Cenetron clinical trials group at (512) 439-2000.  
Ordering Process: 
• 
At time of patient randomization, provide the contact for kit ordering in OPEN 
• 
Following randomization of the patient to the trial, go to the website 
www.cenetron.com and click on the ‘Order Kits’ button at the top right. It is 
recommended that kits be ordered same day as patient randomization. 
• 
The order form is not study specific and can be used for any study. Complete the 
online form as follows: 
o Sponsor (REQUIRED): ECOG-ACRIN 
o Contact Name (REQUIRED): Name of the site kit contact. Should match the 
name of the individual provided in OPEN as the kit contact 
o Protocol Number (REQUIRED): EA8153 
o Phone Number (REQUIRED): Phone number of the kit contact. Please ensure 
that this is a number that can be reached from an external caller 
o Site Number (REQUIRED): Institution NCI Site ID 
o FAX Number: Fax number of the kit contact 
o Investigator: Last name of the kit contact is adequate 
o Email (REQUIRED): Email of the site kit contact. Must be entered twice to 
confirm 
o Date Supplies Needed (REQUIRED): Add three (3) business days or more to 
order date. (E.g. if ordering on 2/5/2016, indicate 2/10/2016 to accommodate the 
weekend. Reminder that holidays must also be considered in this timeline) 
o KIT NAME (REQUIRED): EA8153 Collection Kit 
o Quantity: 1 
o 
Comments: Provide EA8153 Patient Case ID# and full shipping address 
• 
‘Patient Case ID =’ ##### 
• 
‘Ship Kit to’ name of the individual to whom the kit is being shipped. (May be 
different than the kit contact provided above) 
• 
Full street address, town, state and zip code 
o Answer the security question 
Please complete this form correctly, including the valid ECOG-ACRIN patient case 
number and complete shipping address. If information is missing the kit 
processing will be delayed. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
82 
Cabazitaxel with Abiraterone versus Abiraterone alone Randomized Trial for Extensive 
Disease following Docetaxel: the CHAARTED2 Trial 
 
Appendix V 
 
EA8153 Cabazitaxel Study Drug Request Form and EA8153 Investigational Product 
Destruction Record Download Instructions 
Downloading the EA8153 Cabazitaxel Study Drug Request Form and EA8153 
Investigational Product Destruction Record: These forms are available for download 
from the EA8153 protocol page located on the CTSU members’ website. 
• 
Go to https://www.ctsu.org and log in to the members’ area using your CTEP-
IAM username and password 
• 
Click on the Protocols tab in the upper left of your screen 
• 
Click on the ECOG-ACRIN link to expand, then select trial protocol EA8153 
• 
Click on Documents tab, select the Pharmacy tab, and download and complete 
the forms provided. 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
83 
Cabazitaxel with Abiraterone versus Abiraterone alone Randomized Trial for Extensive 
Disease following Docetaxel: the CHAARTED2 Trial 
 
Appendix VI 
 
Ancillary for Tobacco Use Assessment: EAQ16T 
Study Co-Chairs:  Elyse Park, Ilana Gareen, Lynne Wagner, Jamie Ostroff, Ben Herman 
Patients registered to selected ECOG-ACRIN trials are eligible to participate in this ancillary 
study, once the appropriate amendment incorporating the study is activated. 
The Ancillary for Tobacco Use Assessment is a project that seeks to address questions about 
patient-reported tobacco use and smoking behaviors that may span several studies and/or 
diseases. The tobacco use ancillary is embedded into parent protocols, with participation in the 
ancillary informed in the parent consent form and participation determined via providing email 
address to the sites. The general objectives of the tobacco use ancillary are not specific to any 
single parent protocol; however, specific objectives may be included in the parent or related 
parent protocols. 
A significant proportion of cancer patients are current smokers at the time of cancer diagnosis,1–
5 and there are known risks associated with continued smoking following cancer diagnosis. 
These include decreased survival time; increased complications from surgery, radiation, and 
chemotherapy; and increased risk of second primary tumors.6–11 As such, the National 
Comprehensive Cancer Network (NCCN), the American Association of Cancer Research 
(AACR) and the American Society of Clinical Oncology (ASCO) have identified persistent 
smoking as a modifiable risk factor and recommend cessation counseling for cancer patients 
who smoke. Although evidence-based guidelines for treating tobacco dependence exist,12 they 
have not yet been well-integrated into cancer care settings. Moreover, knowledge regarding the 
scope and patterns of tobacco use among cancer patients is limited.  As a critical step in closing 
this knowledge gap, the NCI-AACR Cancer Patient Tobacco Use Asssessment Task Force 
developed the Cancer Patient Tobacco Use 1–4,13,14 Questionnaire (C-TUQ). Through this 
ancillary, the modified C-TUQ measures will be administered to participants enrolling in selected 
Phase II and Phase III ECOG ACRIN (EA) therapeutic trials. 
The major questions may be summarized: 
1. What is the smoking status of cancer patients enrolled on EA clinical trials? 
2. Do patients quit smoking or try to quit smoking after receiving a cancer diagnosis? 
3. What forms of tobacco use do patients engage in? 
4. What assistance do patients use or receive to try to quit? 
5. How does tobacco use, other forms of tobacco use, and/or environmental tobacco exposure 
affect patient’s treatment toxicity, patient-reported physical and psychological symptoms, 
trial adherence, and therapeutic outcomes? 
When patients consent to participate, they will be asked to provide a contact email address and 
that address along with their registration information will be sent directly from the parent trial’s 
registration system to ECOG-ACRIN Systems for Easy Entry of Patient Reported Outcomes 
(EASEE-PRO), and the patient will be automatically registered into EASEE-PRO for 
participation.  To activate their account for self-directed web entry of surveys, the system will 
send an activation message to the contact email address that will explain how to activate their 
account for self-directed web entry of surveys.  After their account is activated, the patient will 
Rev. Add#2 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
84 
be able to complete questionnaires using a secure browser interface from any web enabled 
computer, tablet, or mobile device. 
Measures 
The selected Core and Extension C-TUQ items will be assessed. The 4-item Short Form 
PROMIS® for anxiety and depression, the Lung Cancer Stigma Scale, and six symptom items 
(general pain, fatigue, nausea, cough, insomnia, shortness of breath) from FACIT (Functional 
Assessment of Chronic Illness Therapy)) together with modifications of these same six 
questions to address the degree of bother associated with each symptom will be administered 
as well. Additionally, we will ask participants’ perceptions of how smoking improves or worsens 
each of the six symptom experience. All these items will be compiled into Survey of Tobacco 
Use (STU) (baseline and follow-up). 
Contents and Corresponding Questions in Survey of Tobacco Use (STU) 
Dimension 
Source of Measures 
Baseline STU 
Follow-up STU 
Basic Tobacco Use Information 
C-TUQ 
Q1 – Q5 
Q1 – Q2 
Tobacco Use in Relation to Cancer 
Diagnosis and Treatment 
C-TUQ 
Q6 – Q7 
Q3 
Smoking Cessation, Cessation 
Products, and Assistance Methods 
C-TUQ 
Q8 – Q13 
Q4 – Q9 
Use of Other Products  
C-TUQ 
Q14 
Q10 
Second-Hand Smoke Exposure 
C-TUQ 
Q15 – Q16 
Q11 – Q12 
Psychological Symptoms 
PROMIS  
Lung Cancer Stigma 
Scale 
Q17 – Q18 
Q13 – Q14 
Physical Symptoms 
FACIT 
Q19 
Q15 
Sociodemographics 
 
Q20 – 21 
 
NOTE: 
In order to minimize ambiguity and assure that patients are oriented to answer 
appropriately, the specific phrasing of items may vary depending specific cancer type 
and treatment. 
Tobacco Use. The selected Core and Extension C-TUQ items (from categories of Basic 
Tobacco Use Information, Tobacco Use in Relation to Cancer Diagnosis and Treatment, 
Smoking Cessation/Cessation Products/Assistance Methods, Use of Other Products, and 
Second-Hand Smoke Exposure) will be assessed in the baseline and follow-up Survey of 
Tobacco Use. 
Oncology Provider Assistance. C-TUQ Question 13 assesses “cancer doctors” Advise. We 
will add 4 As to assess participants’ reported 5As (Ask (Q12a), Advise (Q12b), Assess (Q12c), 
Assist (Q12d-Q12f), and Arrange follow-up (Q12g), as in Baseline STU).80 
Psychological Symptom Assessment. Anxiety & Depression: (The Patient Reported 
Outcomes Measurement Information System (PROMIS®)). We will administer the 4-item Short 
Form PROMIS® for anxiety and depression (Q17 in Baseline STU).  Stigma: The Lung Cancer 
Stigma scale measures the extent to which shame is internalized (Q18 in Baseline STU).81 
Physical Symptom Assessment Physical Symptom Assessment (Functional Assessment of 
Chronic Illness Therapy (FACIT)). FACIT, a measurement system with a collection of quality-of-
life questionnaires, expands the more familiar FACT (Functional Assessment of Cancer 
Therapy) questionnaires into other chronic illness and conditions. FACIT consists of many 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
85 
individual questions to assess various symptoms from the patient perspective. We will use 6 
FACIT items, selected based on the therapeutic regimens, expected toxicity, and malignancy 
type of the parent trials. In addition, we have created modifications of these same six questions 
to address the degree of bother associated with each symptom” The symptoms of general pain, 
fatigue, nausea, cough, sleep difficulty, and shortness of breath will be assessed, first using the 
standard and validated FACT item, and then asking the degree of “bother” imposed by each 
symptom, on the same 5-point scale. These clusters of symptoms were specifically chosen 
based on potential interactions between tobacco use and longitudinal symptoms. 
Sociodemographic Variables. Sociodemographic variables, including age, sex, zip code, and 
race/ethnicity are collected for all NCTN trial participants at registration.  At baseline, 
participants will provide information on marital status (Q20 in Baseline STU) and education level 
(Q21 in Baseline STU) as part of the tobacco supplemental assessment. 
Cancer Treatment Variables. Clinical variables including date of diagnosis, malignancy type 
(smoking related vs. non-smoking related, cancer stage), and treatment details (i.e. types and 
dates of surgery, chemotherapy, and/or radiation received), along with disease status and 
survival, will be captured in Medidata Rave via the parent protocol and will be available for 
analysis of the ancillary. Provider-assessed adverse events will also be captured via the parent 
protocol in Medidata Rave, using case report forms commonly used across the NCTN and using 
standard data elements. 
Assessments 
All items in Survey of Tobacco Use will be administered using the EASEE-PRO system. The 
advantage of our virtual electronic data capture system is that our proposed assessments will 
not be limited to, or dependent upon, patient trial visits.  Confidential and potentially stigmatizing 
information can be provided without requiring direct contact with the care team. 
Timing of Assessments 
Given the critical questions that remain13 about the timing of conducting tobacco use 
assessments, we have carefully chosen to collect tobacco assessment data at trial enrollment, 3 
and 6 month follow-up.  For tobacco treatment trials, 6 month follow-up is the recommended 
primary outcome time point. By 6 month follow-up, most cancer treatment-related quitting 
activity62, cancer treatment initiation of therapy, and FDA-approved smoking cessation 
medication regimens will be completed. Adverse events during treatment will have been 
observed. 
Statistical Considerations and Analysis Plans 
The analysis plans described below are planned for a combined analysis of the data from the 8 
selected ECOG-ACRIN trials. Consistency in the effects over the studies would be examined in 
this analysis. 
1. CHANGES IN SMOKING STATUS AND EXPOSURE. At baseline, combustible tobacco use 
(1a) will be characterized by smoking status (never smoker, former smoker, and current 
smoker based on Baseline STU Qs 1 and 5), other forms of tobacco use (1b) will be a 
composite variable determined by non-cigarette items (based on Baseline STU Q7 and 
Q14), and environmental tobacco smoke (ETS) level (1c) will be determined by current 
household and work exposure (Baseline STU Qs 15-16). At follow-up, combustible tobacco 
use (1a) will be examined by smoking status (Follow-up STU Qs 1 and 2), other forms of 
tobacco use (1b) will be determined by Follow-up STU Q10, and ETS level (1c) will be 
determined by 30 day household and work exposure (Follow-up STU Qs 11-12). We will 
examine tobacco use at baseline, 3 and 6 month follow-up, and change in status 
(abstinence in combustible tobacco, abstinence of other forms of tobacco use, and change 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
86 
in exposure to smoke-free home and work) using summary statistics (frequency and 
proportion). We will explore the effects of sociodemographic and cancer treatment factors 
on smoking status using logistic regression (comparing smokers and non-smokers). We will 
also evaluate factors associated with changes in smoking status. 
2. TREATMENT TOXICITY. The selected trials capture information about adverse events 
during treatment using NCI’s Common Terminology Criteria for Adverse Events, Version 4. 
Toxicities are measured at each treatment visit and graded according to severity, with grade 
1 corresponding to mild toxicity and grade 5 signifying a lethal adverse event.  We will 
determine each patient’s worst degree toxicity across all event types and treatment visits 
and will compare the distribution of worst degree grades between smokers and non-
smokers and between patients with environmental tobacco exposure and those without 
exposure using exact tests. We will also examine the distribution of worst degree grades 
between users with different form of tobacco use. In addition, we will explore the effects of 
tobacco use on dose modifications (yes vs. no) using logistic regression, with each patient’s 
dose modification status determined across all treatment visits. 
3. SYMPTOM BURDEN. Tobacco variables will be conceptualized as described in the section 
of CHANGES IN SMOKING STATUS AND EXPOSURE. Tobacco use status (as measured 
at baseline, 3 and 6 month follow-up) will be compared to physical and psychological 
symptom burden (as measured at each corresponding time points). At 3 and 6 month follow-
up, we will also examine the association between tobacco use changes and changes in 
symptom burden. We will explore the effects of sociodemographic and cancer treatment 
factors on symptom burden using repeated measures mixed effects models. As an example 
of statistical power, we consider the PROMIS SF-4 depression measure. We assume that 
1500 patients will be enrolled across the 8 parent studies over 13 months, and that 20% are 
smokers. We assume that 85% of patients will have assessments at 6 months. Given 
groups of these sizes (26 quitters and 230 still-smokers) and standard deviation of 4.08 for 
the PROMIS SF-4 depression scale, there will be 83% power to detect a difference in 
change scores of 2.5 between groups using a two-sample t-test with Type I error of 5%.  
The minimally important difference for this instrument is 2.2.79 
4. CESSATION PATTERNS AND TREATMENT. At baseline we will explore pre-treatment 
combustible tobacco use patterns (STU Q6a and Q6b), quitting behaviors (STU Q13), 
behavioral program utilization (STU Q11) and oncology provider support (5As, STU Q12), 
and smoking cessation medication use (STU Q10). At follow-up we will explore post-
treatment combustible tobacco use patterns (STU Q3a-Q3e), quitting behaviors (STU Q9), 
behavioral program utilization (STU, Q7) and oncology provider support (5As, STU Q8), and 
smoking cessation medication use (STU Q6). We will explore the effects of 
sociodemographic and cancer treatment factors on these variables. We will examine 
associations of quitting behaviors and behavioral and medication utilization with tobacco use 
status (as outlined in the section of CHANGES IN SMOKING STATUS AND EXPOSURE) at 
baseline and on respective 3 and 6 month tobacco outcomes. These analyses will be 
descriptive in nature. Summary statistics (frequency, proportions, and 95% confidence 
intervals) will be used. 
5. TRIAL OUTCOMES. We will compare treatment duration between smokers and non-
smokers and between patients with environmental tobacco exposure and those without 
exposure. Cumulative incidence/competing risk methods will be used to estimate time to 
treatment discontinuation for adverse events, disease progression, completion per protocol, 
or other causes. Gray’s test will be used to test for differences in the cumulative incidence 
distributions.78 Differences in the distribution of reasons for discontinuation of treatment will 
be examined using exact tests. Relative dose intensity is defined as the ratio of actually 
delivered dose intensity to the planned dose intensity. The effects of tobacco use and 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
87 
exposure on relative dose intensity (≥ 90% vs. < 90%) will be explored using logistic 
regression. Differences in the primary endpoint and important secondary endpoints will be 
examined using log rank test and exact test (as appropriate). 
Data collected in the tobacco use project will support a range of analyses. Precise estimates of 
power will depend on the prevalence of smoking at baseline among study participants, the 
proportion whose smoking status changes, and the duration and adequacy of follow-up. 
References 
1. YI, Yang P, Parkinson J, Zhao X, Wampfler JA, Ebbert JO, Sloan JA. The 
relationship between cigarette smoking and quality of life after lung cancer diagnosis. 
Chest. 2004; 126(6):1733-1741.doi: 10.1378/chest.126.6.1733. 
2. Gritz E. Rationale for Treating Tobacco Dependence in the Cancer Setting. 
Conference presentation at: Treating Tobacco Dependence at the National Cancer 
lnstitute's Cancer Centers. December 2009. 
3. Park ER, Japuntich SJ, Rigotti NA, Traeger L, He Y, Wallace RB, Malin JL, Zallen 
JP, Keating NL. A snapshot of smokers after lung and colorectal cancer diagnosis. 
Cancer. 2012;118(12):3153-3164. doi: 10.1002/cncr.26545. 
4. Bellizzi KM, Rowland JH, Jeffery DD, McNeel T. Health behaviors of cancer 
survivors: examining opportunities for cancer control intervention. J Clin Oneal Off J 
Am Soc Clin Oneal. 2005;23(34):8884- 8893. doi: 10.1200/JC0.2005.02.2343. 
5. Underwood JM, Townsend JS, Tai E, White A, Davis SP, Fairley TL. Persistent 
cigarette smoking and other tobacco use after a tobacco-related cancer diagnosis. J 
Cancer Surviv Res Pract. 2012;6(3):333- 344. doi: 10.1007/s11764-012-0230-1. 
6. Dresler CM. Is it more important to quit smoking than which chemotherapy is used? 
Lung Cancer Arnst Neth. 2003;39(2): 119-124. 
7. Shen T, Le W, Yee A, Kamdar 0, Hwang PH, Upadhyay D. Nicotine induces 
resistance to chemotherapy in nasal epithelial cancer. Am J Rhino/ Allergy. 
2010;24(2):e73-77. doi:10.2500/ajra.2010.24.3456. 
8. Chen AM, Chen LM, Vaughan A, Sreeraman R, Farwell DG, Luu Q, Lau DH, Stuart 
K, Purdy JA, Vijayakumar S. Tobacco smoking during radiation therapy for head-
and-neck cancer is associated with unfavorable outcome. Int J Radiat Oneal Biol 
Phys. 2011;79(2):414-419. doi: 10.1016/j.ijrobp.2009.10.050. 
9. Garces YI, Schroeder DR, Nirelli LM, Croghan GA, Croghan IT, Foote RL, Hurt RD. 
Second primary tumors following tobacco dependence treatments among head and 
neck cancer patients. Am J Clin Oneal. 2007;30(5):531-539. doi: 
10.1097/COC.Ob013e318059adfc. 
10. Richardson GE, Tucker MA, Venzon DJ, Linnoila RI, Phelps R, Phares JC, Edison 
M, Ihde DC, Johnson BE. Smoking cessation after successful treatment of small-cell 
lung cancer is associated with fewer smoking-related second primary cancers. Ann 
Intern Med. 1993;119(5):383-390. 
11. Tucker MA, Murray N, Shaw EG, Ettinger OS, Mabry M, Huber MH, Feld R, 
Shepherd FA, Johnson DH, Grant SC, Aisner J, Johnson BE. Second primary 
cancers related to smoking and treatment  of small-cell lung cancer. Lung Cancer 
Working Cadre. J Natl Cancer Inst. 1997;89(23): 1782-1788. 
12. Clinical Practice Guideline Treating Tobacco Use and Dependence 2008 Update 
Panel, Liaisons, and Staff. A clinical practice guideline for treating tobacco use and 
dependence: 2008 update. A U.S. Public Health Service report. Am J Prev Med. 
2008;35(2): 158-176. doi: 10.1016/j.amepre.2008.04.009. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
88 
13. Land SR, Toll BA, Moinpour CM, Mitchell SA, Ostroff JS, Hatsukami DK, Duffy SA, 
Gritz ER, Rigotti NA, Brandon TH, Prindiville SA, Sarna LP, Schnall RA, Herbst RS, 
Cinciripini PM, Leischow SJ, Dresler CM, Fiore MC, Warren  GW. Research 
Priorities, Measures, and Recommendations  for Assessment  of   Tobacco Use in 
Clinical Cancer Research. Clin Cancer Res Off J Am Assoc Cancer Res. 
2016;22(8):1907-1913. doi:10.1158/1078-0432.CCR-16-0104. 
14. Nishihara R, Morikawa T, Kuchiba A, Lochhead P, Yamauchi M, Liao X, Imamura Y, 
Nosho K, Shima K, Kawachi I, Qian ZR, Fuchs CS, Chan AT, Giovannucci E, Ogino 
S. A prospective study of duration of smoking cessation and colorectal cancer risk by 
epigenetics-related tumor classification. Am J Epidemiol. 2013;178(1):84-100. 
doi:10.1093/aje/kws431. 
15. Yang H-K, Shin D-W, Park J-H, Kim S-Y, Eom C-S, Kam S, Choi J-H, Cho B-L, Seo 
H-G. The association between perceived social support and continued smoking in 
cancer survivors. Jpn J Clin Oneal. 2013;43(1 ):45-54.  doi:10.1093/jjco/hys182. 
16. Tseng T-S, Lin H-Y, Moody-Thomas S, Martin M, Chen T. Who tended to continue 
smoking after cancer diagnosis: the national health and nutrition examination survey 
1999-2008. BMC Public Health.2012; 12:784.  doi: 10.1186/1471-2458-12-784. 
17. Joshu CE, Mondul AM, Meinhold CL, Humphreys EB, Han M, Walsh PC, Platz EA. 
Cigarette  smoking and prostate cancer recurrence after prostatectomy. J Natl 
Cancer Inst. 2011 ;103(10):835-838.doi: 10.1093/jnci/djr124. 
18. Fleshner N, Garland J, Moadel A, Herr H, Ostroff J, Trambert R, O'Sullivan M, Russo 
P. Influence of smoking status on the disease-related outcomes of patients with 
tobacco-associated superficial transitional cell carcinoma of the bladder. Cancer. 
1999;86(11):2337-2345. 
19. Rice D, Kim H-W, Sabichi A, Lippman S, Lee JJ, Williams B, Vaporciyan A, Smythe 
WR, Swisher S, Walsh G, Putnam JB, Hong WK, Roth J. The risk of second primary 
tumors after resection of stage I nonsmall cell lung cancer. Ann Thorac Surg. 
2003;76(4):1001-1007-1008. 
20. Do K-A, Johnson MM, Doherty DA, Lee JJ, Wu XF, Dong Q, Hong WK, Khuri FR, Fu 
KK, Spitz MR. Second primary tumors in patients with upper aerodigestive tract 
cancers: joint effects of smoking and alcohol (United States). Cancer Causes Contra/ 
CCC. 2003;14(2):131-138. 
21. National Center for Chronic Disease Prevention and Health Promotion (US) Office on 
Smoking and Health. The Health Consequences of Smoking-50 Years of Progress: A 
Report of the Surgeon General. Atlanta (GA): Centers for Disease Control and 
Prevention (US); 2014. http://www.ncbi.nlm.nih.gov/books/NBK179276/. Accessed 
July 8, 2016. 
22. Gritz ER, Fingeret MC, Vidrine DJ, Lazev AB, Mehta NV, Reece GP. Successes and 
failures of the teachable moment: smoking cessation in cancer patients. Cancer. 
2006;106(1):17-27. doi:10.1002/cncr.21598. 
23. Parsons A, Daley A, Begh R, Aveyard P. Influence of smoking cessation after 
diagnosis of early stage lung cancer on prognosis: systematic review of 
observational studies with meta-analysis. BMJ. 2010;340:b5569. 
24. Yang B, Jacobs EJ, Gapstur SM, Stevens V, Campbell PT. Active smoking and 
mortality among colorectal cancer survivors: the Cancer Prevention Study II nutrition 
cohort. J Clin Oneal Off J Am Soc Clin Oneal. 2015;33(8):885-893. doi: 
10.1200/JC0.2014.58.3831. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
89 
25. Daniel M, Keefe FJ, Lyna P, Peterson B, Garst J, Kelley M, Bepler G, Bastian LA. 
Persistent smoking after a diagnosis of lung cancer is associated with higher 
reported pain levels. J Pain Off J Am Pain Soc. 2009; 10(3):323-328. doi: 
10.1016/j.jpain.2008.10.006. 
26. Danson SJ, Rowland C, Rowe R, Ellis S, Crabtree C, Horsman JM, Wadsley J, 
Hatton MQ, Woll PJ, Eiser C. The relationship between smoking and quality of life in 
advanced lung cancer patients: a prospective longitudinal study. Support Care 
Cancer Off J Multinatl Assoc Support Care Cancer. 2016;24(4): 1507- 1516.  doi: 
10.1007/s00520-015-2928-x. 
27. McBride CM, Ostroff JS. Teachable moments for promoting smoking cessation: the 
context of cancer care and survivorship. Cancer Control J Moffitt Cancer Cent. 
2003;10(4):325-333. 
28. Zhang J, Kamdar 0, Le W, Rosen GD, Upadhyay D. Nicotine induces resistance to 
chemotherapy by modulating mitochondrial signaling in lung cancer. Am J Respir 
Cell Mo/ Biol. 2009;40(2): 135-146. doi: 10.1165/rcmb.2007-02770C. 
29. Tsurutani J, Castillo SS, Brognard J, Granville CA, Zhang C, Gills JJ, Sayyah J, 
Dennis PA. Tobacco components stimulate Akt-dependent proliferation and 
NFkappaB-dependent survival in lung cancer cells. Carcinogenesis. 2005;26(7): 
1182-1195. doi: 10.1093/carcin/bgi072. 
30. Zevallos JP, Mallen MJ, Lam CY, Karam-Hage M, Blalock J, Wetter OW, Garden AS, 
Sturgis EM, Cinciripini PM. Complications of radiotherapy in laryngopharyngeal 
cancer: effects of a prospective smoking cessation program. Cancer. 
2009;115(19):4636-4644. doi:10.1002/cncr.24499. 
31. Vaporciyan AA, Merriman KW, Ece F, Roth JA, Smythe WR, Swisher SG, Walsh  
GL, Nesbitt JC,  Putnam JB. Incidence of major pulmonary morbidity after 
pneumonectomy: association with timing of smoking cessation. Ann Thorac Surg. 
2002;73(2):420-425-426. 
32. Xu J, Huang H, Pan C, Zhang B, Liu X, Zhang L. Nicotine inhibits apoptosis induced 
by cisplatin in human oral cancer cells. Int J Oral Maxillofac Surg. 2007;36(8):739-7 
44. doi: 10.1016/j.ijom.2007 .05.016. 
33. Kelemen LE, Warren GW, Koziak JM, Kobel M, Steed H. Smoking may modify the 
association between neoadjuvant chemotherapy and survival from ovarian cancer. 
Gynecol Oneal. 2016;140(1):124-130.doi: 10.1016/j.ygyno.2015.11.008. 
34. Jung KH, Kim SM, Choi MG, Lee JH, Noh JH, Sohn TS, Bae JM, Kim S. 
Preoperative smoking cessation can reduce postoperative complications in gastric 
cancer surgery. Gastric Cancer Off J Int Gastric Cancer Assoc Jpn Gastric Cancer 
Assoc. 2015;18(4):683-690. doi:10.1007/s10120-014-0415-6. 
35. Rigotti NA. The future of tobacco treatment in the health care system. Ann Intern 
Med. 2009; 150(7):496- 497. 
36. Geller AC, Brooks DR, Powers CA, Brooks KR, Rigotti NA, Bognar B, McIntosh S, 
Zapka J. Tobacco cessation and prevention practices reported by second and fourth 
year students at US medical schools. J Gen Intern Med. 2008;23(7):1071-1076. 
doi:10.1007/s11606-008-0526-z. 
37. Albers AB, Biener L, Siegel M, Cheng OM, Rigotti N. Household smoking  bans and 
adolescent antismoking attitudes and smoking initiation: findings from a longitudinal 
study of a Massachusetts youth cohort. Am J Public Health. 2008;98(10):1886-1893. 
doi:10.2105/AJPH.2007.129320. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
90 
38. Thorndike AN, Regan S, Rigotti NA. The treatment of smoking by US physicians 
during ambulatory visits: 1994 2003. Am J Public Health. 2007;97(10): 1878-1883. 
doi: 10.2105/AJPH.2006.092577. 
39. Public Law 111-5. The American Recovery and Reinvestment Act of 2009. 
2009;155:115-521. 
40. Blumenthal D, Tavenner M. The "meaningful use" regulation for electronic health 
records. N Engl J Med. 2010;363(6):501-504. doi: 10.1056/NEJMp1006114. 
41. Toll BA, Brandon TH, Gritz ER, Warren GW, Herbst RS, AACR Subcommittee on 
Tobacco and Cancer. Assessing tobacco use by cancer patients and facilitating 
cessation: an American Association for Cancer Research policy statement. Clin 
Cancer Res Off J Am Assoc Cancer Res. 2013;19(8):1941-1948. doi:10.1158/1078-
0432.CCR-13-0666. 
42. Quality Oncology Practice Initiative (QOPI®) I ASCO Institute For Quality. 
http://www.instituteforquality.org/quality-oncology-practice-initiative-qopi. Accessed 
July 8, 2016. 
43. Shields PG. New NCCN Guidelines: Smoking Cessation for Patients With Cancer. J 
Natl Compr Cancer Netw JNCCN. 2015; 13(5 Suppl):643-645. 
44. de Moor JS, Elder K, Emmons KM. Smoking prevention and cessation interventions 
for cancer survivors. Semin Oneal Nurs. 2008;24(3):180-192. 
doi:10.1016/j.soncn.2008.05.006. 
45. Gritz ER, Nisenbaum R, Elashoff RE, Holmes EC. Smoking behavior following 
diagnosis in patients with stage I non-small cell lung cancer. Cancer Causes Control 
CCC. 1991;2(2):105-112. 
46. Dresler CM, Bailey M, Roper CR, Patterson GA, Cooper JD. Smoking cessation and 
lung cancer resection. Chest. 1996;110(5):1199-1202. 
47. Sanderson Cox L, Patten CA, Ebbert JO, Drews AA, Croghan GA, Clark MM, Wolter 
TD, Decker  PA, Hurt RD. Tobacco use outcomes among patients with lung cancer 
treated for nicotine dependence. J Clin Oneal Off J Am Soc C/in Oneal. 
2002;20(16):3461-3469. 
48. Schnoll RA, Zhang B, Rue M, Krook JE, Spears WT, Marcus AC, Engstrom PF. Brief 
physician-initiated quit-smoking strategies for clinical oncology settings: a trial 
coordinated by the Eastern Cooperative Oncology Group. J Clin Oneal Off J Am Soc 
Clin Oneal. 2003;21 (2):355-365. 
49. Sarna L. Smoking behaviors of women after diagnosis with lung cancer. Image-- J 
Nurs Scholarsh.1995;27(1):35-41. 
50. Cooley ME, Emmons KM, Haddad R, Wang Q, Posner M, Bueno R, Cohen T-J, 
Johnson BE. Patient- reported receipt of and interest in smoking-cessation 
interventions after a diagnosis of cancer. Cancer. 2011; 117(13):2961-2969. doi: 
10.1002/cncr.25828. 
51. Cancer Facts and Statistics I American Cancer Society. 
http://www.cancer.org/research/cancerfactsstatistics/. Accessed January 27, 2016. 
52. de Dios MA, Anderson BJ, Stanton C, Audet DA, Stein M. Project Impact: a 
pharmacotherapy pilot trial investigating the abstinence and treatment adherence of 
Latino light smokers. J Subst Abuse Treat. 2012;43(3):322-330. doi: 
10.1016/j.jsat.2012.01.004. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
91 
53. Park ER, Japuntich SJ, Traeger L, Cannon S, Pajolek H. Disparities between blacks 
and whites in tobacco and lung cancer treatment. The Oncologist. 2011;16(10):1428-
1434.doi: 10.1634/theoncologist.2011-0114. 
54. Warren GW, Marshall JR, Cummings KM, Toll B, Gritz ER, Hutson A, Dibaj S, Herbst 
R, Dresler C, IASLC Tobacco  Control and Smoking Cessation  Committee. Practice 
patterns and perceptions of thoracic oncology providers on tobacco use and 
cessation in cancer patients. J Thorac Oneal Off Pub/ Int Assoc Study Lung Cancer.  
2013;8(5):543-548. doi:10.1097/JTO.Ob013e318288dc96. 
55. Warren GW, Marshall JR, Cummings KM, Toll BA, Gritz ER, Hutson A, Dibaj S, 
Herbst R, Mulshine JL, Hanna N, Dresler CA. Addressing tobacco use in patients 
with cancer: a survey of American Society of Clinical Oncology members. J Oneal 
Pract Am Soc Clin Oneal. 2013;9(5):258-262. doi:10.1200/JOP.2013.001025. 
56. Goldstein AO, Ripley-Moffitt CE, Pathman DE, Patsakham KM. Tobacco use 
treatment at the U.S. National Cancer lnstitute's designated Cancer Centers. 
Nicotine Tob Res Off J Soc Res Nicotine Tob. 2013;15(1 ):52-58. 
doi:10.1093/ntr/nts083. 
57. Warren GW, Dibaj S, Hutson A, Cummings KM, Dresler C, Marshall JR. Identifying 
Targeted Strategies to Improve Smoking Cessation Support for Cancer Patients. J 
Thorac Oneal Off Pub/ Int Assoc Study Lung Cancer. 2015;10(11 ):1532-1537. 
doi:10.1097/JT0.0000000000000659. 
58. Bjurlin MA, Goble SM, Hollowell CMP. Smoking cessation assistance for patients 
with bladder cancer: a national survey of American urologists. J Ural. 2010; 
184(5):1901-1906. doi: 10.1016/j.juro.2010.06.140. 
59. Weaver KE, Danhauer SC, Tooze JA, Blackstock AW, Spangler J, Thomas L, Sutfin 
EL. Smoking cessation  counseling  beliefs and behaviors of outpatient  oncology  
providers.  The Oncologist.  2012; 17(3):455-462. doi: 10.1634/theoncologist.2011-
0350. 
60. Simmons VN, Litvin EB, Unrod M, Brandon TH. Oncology healthcare providers' 
implementation of  the 5A's model of brief intervention for smoking cessation: 
patients' perceptions. Patient Educ Couns. 2012;86(3):414-419. doi: 
10.1016/j.pec.2011.06.016. 
61. Peters EN, Torres E, Toll BA, Cummings KM, Gritz ER, Hyland A, Herbst RS, 
Marshall JR, Warren GW. Tobacco assessment in actively accruing National Cancer 
Institute Cooperative Group Program Clinical Trials. J Clin Oncol Off J Am Soc Clin 
Oncol. 2012;30(23):2869-2875. doi: 10.1200/JC0.2011.40.8815. 
62. Park ER, Japuntich S, Temel J, Lanuti M, Pandiscio J, Hilgenberg J, Davies D, 
Dresler C, Rigotti NA. A smoking cessation intervention for thoracic surgery and 
oncology clinics: a pilot trial. J Thorac Oncol Off Pub/ Int Assoc Study Lung Cancer. 
2011;6(6):1059-1065. doi:10.1097/JTO.Ob013e318215a4dc. 
63. Haas JS, Linder JA, Park ER, Gonzalez I, Rigotti NA, Klinger EV, Kontos EZ, 
Zaslavsky AM, Brawarsky P, Marinacci LX, St Hubert S, Fleegler EW, Williams DR. 
Proactive tobacco cessation outreach to smokers of low socioeconomic status: a 
randomized clinical trial. JAMA Intern Med. 2015; 175(2):218-226. doi:  
10.1001/jamainternmed.2014.6674 
64. Park ER, Puleo E, Butterfield RM, Zorn M, Mertens AC, Gritz ER, Li FP, Emmons 
KM. A process evaluation of a telephone-based peer-delivered smoking cessation 
intervention for adult survivors of childhood cancer: the partnership for health study. 
Prev Med. 2006;42(6):435-442.doi: 10.1016/j.ypmed.2006.03.004. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
92 
65. Emmons KM, Puleo E, Park E, Gritz ER, Butterfield RM, Weeks JC, Mertens A, Li 
FP. Peer-delivered smoking counseling for childhood cancer survivors increases rate 
of cessation: the partnership for health study. J Clin Oncol Off J Am Soc Clin Oncol. 
2005;23(27):6516-6523. doi:10.1200/JC0.2005.07.048. 
66. Fisch MJ, Zhao F, Manola J, Miller AH,  Pirl WF, Wagner LI. Patterns and predictors 
of antidepressant use in ambulatory cancer patients with common solid tumors. 
Psychooncology. 2015;24(5):523-532.doi: 10.1002/pon.3606. 
67. Sanford SD, Zhao F, Salsman JM, Chang VT, Wagner LI, Fisch MJ. Symptom 
burden among young adults with breast or colorectal cancer. Cancer. 2014; 
120(15):2255-2263. doi: 10.1002/cncr.28297. 
68. Hamann HA, Lee J-W, Schiller JH, Horn L, Wagner LI, Chang VT-S, Fisch MJ. 
Clinician perceptions of care difficulty, quality of life, and symptom reports for lung 
cancer patients: an analysis from the Symptom Outcomes and Practice patterns 
(SOAPP) study. J Thorac Oncol Off Pub/ Int Assoc Study Lung Cancer. 
2013;8(12):1474-1483. doi:10.1097/01.JT0.0000437501.83763.5d. 
69. Wagner LI, Robinson D, Weiss M, Katz M, Greipp P, Fonseca R, Cella D. Content 
development for the Functional Assessment of Cancer Therapy-Multiple Myeloma 
(FACT-MM): use of qualitative and quantitative methods for scale construction. J 
Pain Symptom Manage. 2012;43(6):1094-1104.doi: 
10.1016/j.jpainsymman.2011.06.019. 
70. A. Cmelak, Li S, Zhao W, Westra W, Chung C, Gillison M, Gilbert J, Bauman J, 
Wagner L, Ferris R, Trevarthen D, Colevas A, Jahagirdar B, Burtness B. Reduced-
dose IMRT in human papilloma virus (HPV)-associated resectable oropharyngeal 
squamous carcinomas (OPSCC) after clinical complete response (cCR) to induction 
chemotherapy (IC). 2014. 
71. Lewandowski RJ, Andreoli JM, Hickey R, Kallini JR, Gabr A, Baker T, Kircher S, 
Salem R, Kulik L. Angiogenic Response following Radioembolization: Results from a 
Randomized Pilot Study of Yttrium-90 with or without Sorafenib. J Vase lnterv Radio/ 
JVIR. June 2016. doi: 10.1016/j.jvir.2016.03.043. 
72. Mouli S, Hickey R, Thornburg B, Sato KT, Desai K, Gabr A, Kallini JR, Niemeri H, 
Kircher S, Mulcahy MF, Benson Iii AB, Gupta R, Salem R, Lewandowski RJ. Single- 
versus Triple-Drug Chemoembolization for Hepatocellular Carcinoma: Comparing 
Outcomes by Toxicity, Imaging Response, and Survival.  J  Vase lnterv Radio/ JVIR. 
April 2016. doi: 10.1016/j.jvir.2016.01.135. 
73. Hickey R, Lewandowski RJ, Prudhomme T, Ehrenwald E, Baigorri B, Critchfield J, 
Kallini J, Gabr A, Gorodetski B, Geschwind J-F, Abbott A, Shridhar R, White SB, 
Rilling WS, Boyer B, Kauffman S, Kwan S, Padia SA, Gates VL, Mulcahy M, Kircher 
S, Nimeiri H, Benson AB, Salem R. 90Y Radioembolization of Colorectal Hepatic 
Metastases Using Glass Microspheres: Safety and Survival Outcomes from  a 531- 
Patient Multicenter Study. J Nucl Med Off Pub/ Soc Nucl Med. 2016;57(5):665-
671.doi: 10.2967/jnumed.115.166082. 
74. Lewandowski RJ, Memon K, Mulcahy MF, Hickey  R, Marshall K, Williams  M, Salzig  
K, Gates VL, Atassi B, Vouche M, Atassi R, Desai K, Hohlastos E, Sato K, Habib A, 
Kircher S, Newman SB, Nimeiri H, Benson AB, Salem R. Twelve-year experience of 
radioembolization for colorectal hepatic metastases  in 214 patients: survival by era 
and chemotherapy. Eur J Nucl Med Mo/ Imaging. 2014;41(10):1861-1869. doi: 
10.1007/s00259-014-2799-2. 

ECOG-ACRIN 
EA8153 
Cancer Research Group 
Version Date: September 17, 2021 
93 
75. Hickey R, Mulcahy MF, Lewandowski RJ, Gates VL, Vouche M, Habib A, Kircher S, 
Newman S, Nimeiri H, Benson AB, Salem R. Chemoradiation of hepatic 
malignancies: prospective, phase 1 study of full-dose capecitabine with escalating 
doses of yttrium-90 radioembolization. Int J Radiat Oneal Biol Phys. 2014;88(5): 
1025-1031. doi: 10.1016/j.ijrobp.2013.12.040. 
76. Gonzalez A, Japuntich S, Keating NL, Wallace R, He Y, Streck JM, Park ER. Pain 
experiences among a population-based cohort of current, former, and never regular 
smokers with lung and colorectal cancer. Cancer. 2014; 120(22):3554-3561. doi: 
10.1002/cncr.28893. 
77. Park ER, Streck JM, Gareen IF, Ostroff JS, Hyland KA, Rigotti NA, Pajolek H, 
Nichter M. A qualitative study of lung cancer risk perceptions and smoking beliefs 
among national lung screening trial participants. Nicotine Tob Res Off J Soc Res 
Nicotine Tob. 2014; 16(2):166-173. doi: 10.1093/ntr/ntt133. 
78. Gray RJ. A Class of K-Sample Tests for Comparing the Cumulative Incidence of a 
Competing Risk. Ann Stat. 1988;16(3):1141-1154. 
79. Kroenke K, Yu Z, Wu J, Kean J, Monahan PO. Operating Characteristics of PROMIS 
Four-Item Depression and Anxiety Scales in Primary Care Patients with Chronic 
Pain. Pain Med. 2014;15(11):1892- 1901. doi: 10.1111/pme.12537. 
80. Park ER, Gareen IF, Japuntich S, Lennes I, Hyland K, DeMello S, Sicks JD, Rigotti 
NA. Primary Care Provider-Delivered Smoking Cessation Interventions and Smoking 
Cessation Among Participants in the National Lung Screening Trial. JAMA Intern 
Med. 2015;175(9):1509-1516. doi: 10.1001/jamainternmed.2015.2391. 
81. Fife BL, Wright ER. The dimensionality of stigma: a comparison of its impact on the 
self of persons with HIV/AIDS and cancer. J Health Soc Behav. 2000;41 (1):50-67.