Conditions: Prostate Cancer
Keywords: adenocarcinoma of the prostate hormone-resistant prostate cancer stage IV prostate cancer recurrent prostate cancer
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 41
Healthy volunteers: no

Brief summary:
RATIONALE: Androgens can cause the growth of prostate cancer cells. Antiandrogen drugs, such as abiraterone acetate, may lessen the amount of androgens made by the body. It may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying the side effects and how well abiraterone acetate works in treating patients with prostate cancer who have undergone initial hormone therapy.

Detailed description:
OBJECTIVES:

Primary

* To assess the rate of achieving a prostate-specific antigen (PSA) of ≤ 0.2 ng/mL with abiraterone acetate therapy in men with metastatic prostate cancer with a sub-optimal response to androgen-deprivation therapy (ADT).

Secondary

* To assess the overall survival and objective progression-free survival of this group of patients.
* To assess PSA partial response.
* To evaluate the qualitative and quantitative toxicity of abiraterone acetate.

OUTLINE: This is a multicenter study.

Patients receive abiraterone acetate orally daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive androgen blockade with GNRH agonist (goserelin acetate or leuprolide acetate) or a GNRH antagonist (degarelix) per the treating physician and this will be given continuously until evidence of disease progression. Bilateral surgical orchiectomy is also acceptable.

After completion of study therapy, patients are followed up every 3 months for 1 year and then every 6 months for up to 3 years.

Arms:
arm 1: Abiraterone, 1,000 mg, oral (on an empty stomach at least 2 hours after or 1 hour before eating); to be taken daily

Prednisone, 5 mg, oral, 5 mg twice daily

Interventions: intervention 1: abiraterone acetate intervention 2: Prednisone
Intervention descriptions: intervention 1: 1,000 mg, oral (on an empty stomach at least 2 hours after or 1 hour before eating); taken daily intervention 2: 5 mg, oral, 5 mg twice daily

Protocol document:
ICF_001.pdf: 
 
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Informed Consent Model for S1014 
*NOTES FOR LOCAL INSTITUTION INFORMED CONSENT AUTHORS:  
 
This model informed consent form has been reviewed by the DCTD/NCI and is the official 
consent document for this study. Local IRB changes to this document are allowed.  (Institutions 
should attempt to use sections of this document that are in bold type in their entirety.)  Editorial 
changes to these sections may be made as long as they do not change information or intent.  If 
the institutional IRB insists on making deletions or more substantive modifications to the risks or 
alternatives sections, they may be justified in writing by the investigator and approved by the 
IRB.  Under these circumstances, the revised language, justification and a copy of the IRB 
minutes must be forwarded to the SWOG Operations Office for approval before a patient may be 
registered to this study.   
 
Readability Statistics:   
 
Flesch Reading Ease  
60 (targeted above 55) 
Flesch-Kincaid Grade Level 8.5 (targeted below 8.5) 
 
• Instructions and examples for informed consent authors are in [italics].  
• A blank line,  __________, indicates that the local investigator should provide the 
appropriate information before the document is reviewed with the prospective research 
participant.  
• The term "study doctor" has been used throughout the model because the local 
investigator for a cancer treatment trial is a physician.   If this model is used for a trial 
in which the local investigator is not a physician, another appropriate term should be 
used instead of "study doctor".  
• The dates of protocol updates in the header and in the text of the consent is for 
reference to this model only and should not be included in the informed consent form 
given to the prospective research participant.  
• The local informed consent must state which parties may inspect the research records. 
This includes the NCI, the drug manufacturer for investigational studies, any 
companies or grantors that are providing study support (these will be listed in the 
protocol's model informed consent form) and SWOG.  
 
SWOG must be listed as one of the parties that may inspect the research records in all 
protocol consent forms for which patient registration is being credited to SWOG.  This 
includes consent forms for studies where all patients are registered directly through 
SWOG, all intergroup studies for which the registration is being credited to the 
(whether the registration is through the SWOG Data Operations Office or directly 
through the other group), as well as consent forms for studies where patients are 
registered via CTSU and the registration is credited to SWOG. 
• When changes to the protocol require revision of the informed consent document, the 
IRB should have a system that identifies the revised consent document, in order to 
preclude continued use of the older version and to identify file copies.  An appropriate 
method to identify the current version of the consent is for the IRB to stamp the final 


 
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copy of the consent document with the approval date.  The stamped consent document 
is then photocopied for use.  Other systems of identifying the current version of the 
consent such as adding a version or approval date are allowed as long as it is possible 
to determine during an audit that the patient signed the most current version of the 
consent form.  
 
*NOTES FOR LOCAL INVESTIGATORS:  
• The goal of the informed consent process is to provide people with sufficient 
information for making informed choices.   The informed consent form provides a 
summary of the clinical study and the individual's rights as a research participant.  It 
serves as a starting point for the necessary exchange of information between the 
investigator and potential research participant.  This model for the informed consent 
form is only one part of the larger process of informed consent. For more information 
about informed consent, review the "Recommendations for the Development of 
Informed Consent Documents for Cancer Clinical Trials" prepared by the 
Comprehensive Working Group on Informed Consent in Cancer Clinical Trials for the 
National Cancer Institute.  The Web site address for this document is 
http://cancer.gov/clinicaltrials/understanding/simplification-of-informed-consent-docs/ 
• A blank line,  __________, indicates that the local investigator should provide the 
appropriate information before the document is reviewed with the prospective research 
participant.  
• Suggestion for Local Investigators:  An NCI pamphlet explaining clinical trials is 
available for your patients.  The pamphlet is titled: "If You Have Cancer…What You 
Should Know about Clinical Trials".  This pamphlet may be ordered on the NCI Web 
site at https://cissecure.nci.nih.gov/ncipubs or call 1-800-4- CANCER (1-800-422-
6237) to request a free copy.  
• Optional feature for Local Investigators: Reference and attach drug sheets, 
pharmaceutical information for the public, or other material on risks.  Check with your 
local IRB regarding review of additional materials. 
 
*These notes for authors and investigators are instructional and should not be included in the 
informed consent form given to the prospective research participant.  
 


 
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S1014, "Abiraterone Acetate Treatment for Prostate Cancer Patients 
with a PSA of More Than Four Following Initial Androgen Deprivation 
Therapy, Phase II" 
 
This is a clinical trial, a type of research study.  Your study doctor will explain the clinical trial 
to you.  Clinical trials include only people who choose to take part. Please take your time to 
make your decision about taking part.  You may discuss your decision with your friends and 
family.  You can also discuss it with your health care team.  If you have any questions, you can 
ask your study doctor for more explanation.  
 
You are being asked to take part in this study because you have prostate cancer that is only 
partially responding to hormone therapy.  Abiraterone acetate is a hormonal tablet that has been 
approved by the Food and Drug Administration (FDA) for more advanced prostate cancer 
patients who have received chemotherapy.  It is considered investigational for your type of 
prostate cancer.  We will be looking to see if abiraterone acetate improves the effectiveness of 
standard hormonal shots or injections.  The prostate specific antigen (PSA) is a blood test used in 
prostate cancer screening and also to follow prostate cancer.  In this study, we will follow your 
PSA level to help determine if abiraterone acetate is beneficial.  The main goal of this study is to 
see if abiraterone acetate with prednisone reduces PSA. 
 
Who is doing this study? 
 
SWOG is sponsoring this trial.  SWOG is an adult cancer clinical trials organization. SWOG is 
funded through the National Cancer Institute, and its network consists of about four thousand 
physicians at almost three hundred institutions throughout the United States.  Your study doctor 
has met all requirements to be a member of SWOG and to perform National Cancer Institute-
funded research through this Group. 
 
Why is this study being done? 
The purpose of this study is to find out what effects, good and/or bad, abiraterone acetate 
has on you and your prostate cancer.  The effect of the prostate cancer will be measured by 
a blood test (prostatic specific antigen or PSA). 
 
How many people will take part in the study? 
About 38 people will take part in this study.   
 
What will happen if I take part in this research study?   
 
Before you begin the study …  
 


 
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You will need to have the following exams, tests or procedures to find out if you can be in the 
study.  These exams, tests or procedures are part of regular cancer care and may be done even if 
you do not join the study.  If you have had some of them recently, they may not need to be 
repeated.  This will be up to your study doctor. 
 
• History and physical exam including measuring your blood pressure 
• CT scan of your abdomen and pelvis 
• Bone scan 
• Blood prostate specific antigen (PSA) test 
• Other blood tests including those to assess your blood counts, kidney and liver 
function, and testosterone level. 
• CT or MRI scan of the brain if your doctor feels it's necessary 
 
During the study …  
If the exams, tests and procedures show that you can be in the study, and you choose to take part, 
then you will need the following tests and procedures.  They are part of regular cancer care.  
 
Every 2 weeks for the first 3 months: 
• Blood tests to monitor your liver 
 
Every 4 weeks: 
• History and physical exam including measuring your blood pressure 
• Blood prostate specific antigen (PSA) test 
• Other blood tests including those to assess your blood counts, kidney and liver 
function. 
 
Every 12 weeks: 
• CT scan of your abdomen and pelvis 
• Bone scan 
 
Treatment will consist of taking 4 abiraterone acetate tablets a day.  Abiraterone acetate must be 
taken on an empty stomach.  You should not eat for at least two hours before the dose of 
abiraterone acetate and for at least one hour after abiraterone acetate is taken.  You will also take 
one prednisone tablet twice a day.  Prednisone is a type of drug called a corticosteroid.  It is a 
standard treatment for prostate cancer and may improve your symptoms.  Prednisone also 
reduces some of the potential side effects associated with abiraterone acetate.  Abiraterone 
acetate and prednisone can be taken together.  Every 28 days is called a cycle.  You will continue 
taking abiraterone acetate and prednisone as long as your disease does not get worse and side 
effects do not become too severe.  To help keep track of the number of tablets you take and any 
side effects, you will need to keep a pill diary.  The pill diary is called an Intake Calendar and 
you will need to bring it with you for your follow-up visits.  Although it reflects a month's time, 
you should complete it daily.  You need only complete one Intake Calendar for both drugs.   


 
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When I am finished taking abiraterone acetate… 
After you are done taking the study drug, there will be an end of study visit.  A history and 
physical exam with routine blood tests will be done at that time.  The study personnel will 
continue to follow your progress approximately every 3 months for the first year after you join 
the study and then every 6 months thereafter for up to 3 years.  
How long will I be in the study? 
 
You will be asked to take abiraterone acetate for as long as you tolerate the treatment and it is 
working.  After you are finished taking abiraterone acetate, the study doctor will ask you to visit 
the office for follow-up exams for at least up to 3 years from the time you started the study. 
 
Can I stop being in the study? 
 
Yes.  You can decide to stop at any time.  Tell the study doctor if you are thinking about 
stopping or decide to stop.  He or she will tell you how to stop safely.  
 
It is important to tell the study doctor if you are thinking about stopping so any risks from the 
abiraterone acetate can be evaluated by your doctor.  Another reason to tell your doctor that you 
are thinking about stopping is to discuss what follow-up care and testing could be most helpful 
for you. 
 
The study doctor may stop you from taking part in this study at any time if he/she believes it is in 
your best interest, if you do not follow the study rules, or if the study is stopped. 
 
What side effects or risks can I expect from being in the study?  
 
You may have side effects while on the study.  Everyone taking part in the study will be 
watched carefully for any side effects.  However, doctors don’t know all the side effects that 
may happen.  Side effects may be mild or very serious. Your health care team may give you 
medicines to help lessen side effects. Many side effects go away soon after you stop taking 
the abiraterone acetate. In some cases, side effects can be serious, long lasting, or may 
never go away. There also is a risk of death.  
 
There is a small chance of severe allergic reaction to the study drug which may be life-
threatening. Abiraterone acetate may cause harm to the liver. Fewer than 10% of patients 
who took the study drug have had abnormal blood levels of liver enzymes. Rarely, liver 
failure may occur, which can lead to death. Pausing or ending the treatment helped to 
make liver function normal again in most of these cases. Your liver function will be 
checked closely with blood tests every two weeks for the first 3 months of the study and 
then monthly after. If your liver tests are abnormal, the dose of your study drug will be 
reduced or stopped. Abiraterone acetate should be used carefully in patients with a history 
of heart disease. Before treatment with the study drug, high blood pressure must be 


 
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controlled and low potassium must be corrected.  Potassium is needed for proper function 
of your heart, and other important body systems.  
 
You should talk to your study doctor about any side effects that you have while taking part 
in the study.   
 
Risks and side effects related to the abiraterone acetate include those which are: 
 
Frequent (≥ 20%) [May occur in 20 or more patients in 100]  
• hypokalemia (low blood potassium, a mineral that helps regulate heart rate/function, fluid 
balance in the body and is needed for adequate body function) 
• hypertension (high blood pressure) 
 
Very Common (≥ 10% to <20%) [May occur between 10 and 19 patients in 100] 
• edema peripheral (swelling of the legs as a result of the body keeping too much fluid) 
 
Common (≥ 5% to <10%) [May occur between 5 to 9 patients in 100] 
• dyspepsia (uncomfortable feeling in upper belly, indigestion) 
• hematuria (presence of blood in the urine)  
• Alanine aminotransferase increased and/or aspartate aminotransferase increased 
(enzymes in the blood that measure the function of the liver) 
• urinary tract infection 
• fractures (a break in the bone) 
 
Less Common (≥1% to < 5% [May occur in fewer than 5 patients in 100] 
• hypertriglyceridemia (high levels of fats (triglycerides) in the blood)  
• angina pectoris (chest pain from the heart) 
• atrial fibrillation (a fast and irregular heartbeat) 
• tachycardia (rapid heartbeats) 
 
Uncommon (< 1%) [May occur in less than 9 patients in 1000]  
• adrenal insufficiency (decreased function of adrenal glands that normally help maintain 
blood pressure, balance minerals and fluid in your body)  
• cardiac failure (heart failure, the heart is unable to supply enough blood flow to meet the 
body's needs.) 
• arrhythmia (changes in the rhythm of the heart) 
• abnormal ECG with QT prolongation (an abnormal finding on the ECG) 
•  bone density decreased (loss of strength of bones)  
• myopathy (muscle weakness and/or muscle pain) 
 
Unknown (frequency isn’t determined since data was derived from post-marketing experience 
and there was no report from clinical studies) 
• allergic alveolitis (swelling and irritation of the lung) 


 
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• failure of the liver to function (called acute liver failure). 
• Rhabdomyolysis (breakdown of muscle tissue)  
• Torsades de Pointes (rapid or irregular heart rate associated with feeling faint or 
lightheaded) 
 
Possible adverse effects associated with the use of prednisone are: fluid and electrolyte 
disturbances, congestive heart failure in susceptible persons, hypertension, euphoria, 
personality changes, insomnia, mood swings, depression, exacerbation of infection (e.g., 
tuberculosis), exacerbation or symptoms of diabetes, psychosis, muscle weakness, 
osteoporosis, vertebral compression fractures, pancreatitis, esophagitis, peptic ulcer 
disease, dermatologic disturbances, convulsions, vertigo and headache, endocrine 
abnormalities, ophthalmic changes, and metabolic changes. Some patients have 
experienced itching and other allergic, anaphylactic or other hypersensitivity reactions. 
Withdrawal from prolonged therapy may result in symptoms of adrenal insufficiency 
including fever, myalgia and arthralgia. 
 
Reproductive risks:  You should not father a baby while on this study and for at least 1 
week after you stop taking abiraterone acetate. Based on animal studies, abiraterone 
acetate may harm the unborn child.  Male patients who are receiving abiraterone acetate 
and who have a partner of childbearing potential are advised to use a method of birth 
control with adequate barrier protection (e.g. condoms) as determined to be acceptable by 
your study doctor. Check with your study doctor about what kind of birth control methods 
to use and how long to use them.  Some methods might not be approved for use in this 
study.  
 
Handling abiraterone acetate tablets: 
 
This medicine may cause harm to the unborn child if given to women who are pregnant.  It 
should not be taken by women who are breast feeding.  Women who are pregnant or who 
may be pregnant should wear gloves if they need to touch abiraterone acetate tablets.  You 
should notify any caregivers of this information to ensure that appropriate precautions are 
taken.   
 
For more information about risks and side effects, ask your study doctor. 
 
Are there benefits to taking part in the study? 
 
Taking part in this study may or may not make your health better.  While doctors hope 
abiraterone acetate will be more useful against cancer compared to the usual treatment, there is 
no proof of this yet. We do know that the information from this study will help doctors learn 
more about abiraterone acetate as a treatment for prostate cancer.  This information could help 
future cancer patients. 


 
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What other choices do I have if I do not take part in this study? 
 
Your other choices may include: 
• Getting treatment or care for your cancer without being in a study 
• Taking part in another study 
• Getting no treatment 
 
Talk to your doctor about your choices before you decide if you will take part in this study. 
Will my medical information be kept private?  
 
We will do our best to make sure that the personal information in your medical record will be 
kept private.  However, we cannot guarantee total privacy.  Your personal information may be 
given out if required by law.  If information from this study is published or presented at scientific 
meetings, your name and other personal information will not be used.  
 
Organizations that may look at and/or copy your medical records for research, quality assurance, 
and data analysis include: 
• The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), involved in keeping research safe for people 
• SWOG 
• A qualified representative of the manufacturer of abiraterone acetate, Janssen Scientific 
Affairs, LLC. 
 
A description of this study will be available on http://www.clinicaltrials.gov, as required by U.S. 
Law.  This website will not include information that can identify you.  At most, the web site will 
include a summary of the results of the study.  You can search this website at any time. 
 
[Note to Local Investigators: The NCI has recommended that HIPAA regulations be addressed 
by the local institution.  The regulations may or may not be included in the informed consent 
form depending on local institutional policy.] 
 
What are the costs of taking part in this study? 
 
You and/or your health plan/ insurance company will need to pay for some or all of the costs of 
treating your cancer in this study.  Some health plans will not pay these costs for people taking 
part in studies.  Check with your health plan or insurance company to find out what they will pay 
for.  Taking part in this study may or may not cost your insurance company more than the cost of 
getting regular cancer treatment.  
 
Janssen Scientific Affairs, LLC will supply the abiraterone acetate at no charge while you take 
part in this study.  Janssen Scientific Affairs, LLC will also provide funding for distribution of 
drug to the participating treatment sites.  Janssen Scientific Affairs, LLC does not cover the cost 


 
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of getting the abiraterone acetate ready and giving it to you, so you or your insurance company 
may have to pay for this. 
 
Even though it probably won’t happen, it is possible that the manufacturer may not continue to 
provide abiraterone acetate for some reason.  If this would occur, other possible options are:   
• Abiraterone acetate is not currently approved by the FDA for sale in the United States for 
your type of prostate cancer.  If the FDA approves the sale of this drug for your type of 
prostate cancer and if the manufacturer chooses to discontinue supplying the drug free of 
charge for this study, you might be able to get the abiraterone acetate directly from the 
manufacturer or your pharmacy but you or your insurance company may have to pay for 
it. 
• If there is no abiraterone acetate available at all, no one will be able to get more and the 
study would close. 
 
If a problem with getting abiraterone acetate occurs, your study doctor will talk to you about 
these options. 
 
Prednisone, goserelin acetate, leuprolide acetate, and Degarelix are commercially available and 
will not be provided free of charge. 
 
You will not be paid for taking part in this study. 
 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute’s Web site at http://cancer.gov/clinicaltrials/understanding/insurance-coverage.  You 
can print a copy of the "Clinical Trials and Insurance Coverage" information from this Web site. 
 
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and ask them 
to send you a free copy. 
 
What happens if I am injured because I took part in this study? 
 
It is important that you tell your study doctor, __________________ [investigator’s name(s)], if 
you feel that you have been injured because of taking part in this study.  You can tell the doctor 
in person or call him/her at __________________ [telephone number]. 
 
You will get medical treatment if you are injured as a result of taking part in this study.  You 
and/or your health plan will be charged for this treatment.   The study will not pay for medical 
treatment.   
What are my rights if I take part in this study? 
 
Taking part in this study is your choice.  You may choose either to take part or not to take part in 
the study.  If you decide to take part in this study, you may leave the study at any time.   No 
matter what decision you make, there will be no penalty to you and you will not lose any of your 


 
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regular benefits.  Leaving the study will not affect your medical care.  You can still get your 
medical care from our institution.    
 
We will tell you about new information or changes in the study that may affect your health or 
your willingness to continue in the study. 
 
In the case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form.   
 
Who can answer my questions about the study? 
 
You can talk to your study doctor about any questions or concerns you have about this study.  
Contact your study doctor __________________ [name(s)] at __________________ [telephone 
number]. 
 
For questions about your rights while taking part in this study, call the 
________________________ [name of center] Institutional Review Board (a group of people 
who review the research to protect your rights) at __________________ (telephone number).  
[Note to Local Investigator: Contact information for patient representatives or other individuals 
in a local institution who are not on the IRB or research team but take calls regarding clinical 
trial questions can be listed here.]   
 
Please note:  This section of the informed consent form is about additional research 
studies that are being done with people who are taking part in the main study.   
You may take part in these additional studies if you want to.  You can still be a part 
of the main study even if you say 'no' to taking part in any of these additional 
studies. 
 
You can say "yes" or "no" to the following study.  Please mark your choice.   
 
1. 
Future Contact 
I agree to allow my study doctor, or someone approved by my study doctor, to 
contact me regarding future research involving my participation in this study.  
Yes 
No 
 
Where can I get more information? 
 
You may call the National Cancer Institute's Cancer Information Service at:  
 
1-800-4-CANCER (1-800-422-6237) or TTY: 1-800-332-8615 


 
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You may also visit the NCI Web site at http://cancer.gov/ 
 
• For NCI’s clinical trials information, go to: http://cancer.gov/clinicaltrials/ 
 
• For NCI’s general information about cancer, go to http://cancer.gov/cancerinfo/ 
 
You will get a copy of this form.    If you want more information about this study, ask your study 
doctor. 
 
 
Signature 
 
I have been given a copy of all _____ [insert total of number of pages] pages of this form.  I 
have read it or it has been read to me.  I understand the information and have had my questions 
answered.  I agree to take part in this study. 
 
Participant ________________________________ 
 
Date _____________________________________ 

Prot_SAP_002.pdf: 
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PRIVILEGED COMMUNICATION 
FOR INVESTIGATIONAL USE ONLY 
SWOG 
TITLE 
ABIRATERONE ACETATE TREATMENT FOR PROSTATE CANCER PATIENTS WITH A PSA OF 
MORE THAN FOUR FOLLOWING INITIAL ANDROGEN DEPRIVATION THERAPY  
PHASE II 
NCT01309672 
STUDY COORDINATORS: 
AGENTS: 
Thomas W. Flaig, M.D. (Medical Oncology) 
SWOG-held IND Agents: 
University of Colorado Denver 
Abiraterone Acetate (NSC-748121) (IND-111552) 
Medical Oncology/MS 8117 
12801 E. 17th Avenue, Room 8117 
IND-Exempt Agents: 
Aurora CO 80045 
Prednisone (NSC-10023) 
Phone:  303/724-3808 
FAX:  303/724-3889 
E-mail:  thomas.flaig@ucdenver.edu 
BIOSTATISTICIANS: 
Maha H.A. Hussain, M.D. (Medical Oncology) 
Cathy M. Tangen, Dr.P.H. (Biostatistics) 
University of Michigan CCC 
Melissa Plets, M.S. 
Division of Hematology/Oncology 
SWOG Statistical Center 
1500 E. Medical Center Drive 
Fred Hutchinson Cancer Research Center 
7314 CCGC 
1100 Fairview Avenue North, M3-C102 
Ann Arbor, MI  48109-0946 
P.O. Box 19024 
Phone:  734/936-8906 
Seattle, WA  98109-1024 
FAX:  734/615-2719 
Phone:  206/667-4623 
E-mail:  mahahuss@med.umich.edu 
FAX:  206/667-4408 
E-mail:  ctangen@fhcrc.org 
E-mail:  mplets@fhcrc.org  
PARTICIPANTS 
SWOG/SWOG 


 
 
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TABLE OF CONTENTS 
TITLE  ......................................................................................................................................................... 1 
PARTICIPANTS ............................................................................................................................................ 1 
TABLE OF CONTENTS ............................................................................................................................... 2 
1.0 
OBJECTIVES .................................................................................................................................. 4 
1.1 
Primary Objective ............................................................................................................................. 4 
1.2 
Secondary Objectives ...................................................................................................................... 4 
2.0 
BACKGROUND ............................................................................................................................... 4 
3.0 
DRUG INFORMATION .................................................................................................................... 7 
3.1 
Abiraterone Acetate (CB7630) (NSC #748121) (IND-111552) ........................................................ 7 
3.2 
Prednisone (NSC-10023) ............................................................................................................... 15 
4.0 
STAGING CRITERIA ..................................................................................................................... 16 
5.0 
ELIGIBILITY CRITERIA ................................................................................................................ 16 
5.1 
Disease Related Criteria ................................................................................................................ 16 
5.2 
Prior/Concurrent Therapy Criteria .................................................................................................. 17 
5.3 
Clinical/Laboratory Criteria ............................................................................................................. 17 
5.4 
Regulatory Criteria ......................................................................................................................... 18 
6.0 
STRATIFICATION FACTORS ....................................................................................................... 18 
7.0 
TREATMENT PLAN ...................................................................................................................... 19 
7.1 
Good Medical Practice ................................................................................................................... 19 
7.2 
Treatment Schedule ....................................................................................................................... 19 
7.3 
Prior Anti-Androgen Use ................................................................................................................ 20 
7.4 
Intake Calendar .............................................................................................................................. 20 
7.5 
Concomitant Medications ............................................................................................................... 20 
7.6 
Criteria for Removal from Protocol Treatment ............................................................................... 21 
7.7 
Discontinuation of Treatment ......................................................................................................... 21 
7.8 
Follow Up Period ............................................................................................................................ 21 
8.0 
DOSAGE MODIFICATIONS .......................................................................................................... 21 
8.1 
NCI Common Terminology Criteria for Adverse Events ................................................................ 21 
8.2 
Dose Levels of Study Drugs .......................................................................................................... 21 
8.3 
Abiraterone Acetate Dose Modifications ........................................................................................ 22 
8.4 
Prednisone Dose Modifications ..................................................................................................... 22 
8.5 
Dose Modification Contacts ........................................................................................................... 22 
8.6 
Adverse Event Reporting ............................................................................................................... 22 
9.0 
STUDY CALENDAR ...................................................................................................................... 23 
9.1 
Calendar ......................................................................................................................................... 23 
10.0 
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITIONS................................................. 25 
10.1 
Progression Criteria ....................................................................................................................... 25 
10.2 
Symptomatic Deterioration ............................................................................................................. 25 
10.3 
Performance Status ....................................................................................................................... 25 
10.4 
Time to Treatment Failure .............................................................................................................. 26 
10.5 
Time to Death ................................................................................................................................. 26 
10.6 
Undetectable PSA .......................................................................................................................... 26 
10.7 
PSA Partial Response.................................................................................................................... 26 
11.0 
STATISTICAL CONSIDERATIONS .............................................................................................. 26 
11.1 
Accrual Rate ................................................................................................................................... 26 
11.2 
Analysis of Primary Endpoint ......................................................................................................... 26 
11.3 
Analysis of Secondary Endpoints .................................................................................................. 27 
11.4 
Data and Safety Monitoring Committee Oversight ........................................................................ 27 
12.0 
DISCIPLINE REVIEW .................................................................................................................... 27 
13.0 
REGISTRATION GUIDELINES ..................................................................................................... 27 
13.1 
Registration Timing ........................................................................................................................ 27 
13.2 
OPEN Registration Requirements ................................................................................................. 27 
13.3 
Registration procedures ................................................................................................................. 28 
13.4 
Exceptions to SWOG registration policies will not be permitted. ................................................... 29 
14.0 
DATA SUBMISSION SCHEDULE ................................................................................................ 29 
14.1 
Data Submission Requirement ...................................................................................................... 29 


 
 
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14.2 
Master Forms ................................................................................................................................. 29 
14.3 
Data Submission Procedures ........................................................................................................ 29 
14.4 
Data Submission Overview and Timepoints .................................................................................. 30 
15.0 
SPECIAL INSTRUCTIONS............................................................................................................ 31 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS ................................................................... 31 
16.1 
Adverse Event Reporting Requirements........................................................................................ 32 
17.0 
BIBLIOGRAPHY ............................................................................................................................ 36 
18.0 
APPENDIX ..................................................................................................................................... 38 
18.1 
Determination of Expedited Adverse Event Reporting Requirements ........................................... 39 
18.2 
Intake Calendar .............................................................................................................................. 41 
18.3 
Potential Drug Interaction with Abiraterone Acetate ...................................................................... 42 
18.4 
Child-Pugh Classification (CPC) of Liver Dysfunction ................................................................... 43 
 


 
 
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1.0 
OBJECTIVES 
 
1.1 
Primary Objective 
 
To assess the rate of achieving a PSA of ≤ 0.2 ng/ml with abiraterone acetate therapy in 
men with metastatic prostate cancer with a suboptimal response to androgen deprivation 
therapy (ADT).  The undetectable level of PSA will be confirmed by a second 
measurement with a PSA ≤ 0.2 ng/ml at least 4 weeks later, without any evidence for 
progression.  Subjects who fail to reach and confirm a PSA of ≤ 0.2 ng/ml by 12 months 
will be considered a non-responder with regard to the primary endpoint. 
 
1.2 
Secondary Objectives 
 
a. 
To assess the overall survival and objective progression-free survival in this 
group of patients. 
 
b. 
To assess PSA partial response. 
 
c. 
To evaluate the qualitative and quantitative toxicity of abiraterone acetate. 
 
 
2.0 
BACKGROUND 
 
The cornerstone of medical management of metastatic prostate cancer is androgen deprivation 
therapy (ADT).  The clinical utility of ADT was championed by Charles Huggins who reported the 
dramatic effect of ADT in prostate cancer in the 1940’s, in work that led to the Nobel Prize in 
1966.  (1)  ADT was initially achieved through bilateral surgical castration although most men in 
the current era prefer ADT medically via gonadotropin releasing hormone agonist therapy 
(GNRH). 
 
Using data from a SWOG Phase III trial examining the efficacy of continuous versus intermittent 
ADT in men with metastatic disease in SWOG-9346, Hussain and colleagues reported on the 
prognostic value of the PSA nadir after the initial hormone induction portion of the trial.  At the 
end of the 7 month induction period, those patients with a PSA of ≤ 0.2 ng/ml had a median 
survival of 75 months, those with a PSA of 0.2 - 4 ng/ml a survival of 44 months and for those 
patients with a PSA of > 4.0 ng/ml, the median survival was only 13 months.  (2)  This report 
included both non-responders and partial responders.  An additional analysis found that subjects 
who failed to achieve a PSA of < 4 ng/ml and did not exhibit a rising PSA at 7 months had a 
median overall survival of approximately 21 months from this assessment timepoint. 
 
Abiraterone Acetate: Rationale and Background 
 
Developing data suggests that the low levels of androgen that persist despite ADT may play an 
important role in the development of castrate resistant prostate cancer (CRPC).  In both the testis 
and the adrenal glands, cytochrome P 17 (CYP17) catalyzes two key reactions involving the 
enzymes 17α-hydroxylase and C17,20-lyase, converting steroid precursors into androgens.  By 
this mechanism, low levels of circulating testosterone persist despite surgical orchiectomy or 
GNRH agonist/antagonist therapy.  In castrate men, up to 10% of the normal levels of 
testosterone may be observed by this mechanism.  (3)  
 
Alterations and mutations in prostate cancer cells have also been identified as a cause of the 
development of CRPC.  Increased gene expression of CYP17, the enzyme targeted by 
abiraterone acetate, has been correlated with higher stage and Gleason grade in prostate cancer, 
suggesting the possibility of autonomous steroidogenesis in prostate cancer cells.  (4)  Gene 
expression analysis of androgen-sensitive prostate cancer and CRPC reveal increased 
expression of genes capable of converting adrenal androgens into testosterone.  (5)  Surprisingly, 
recent investigations have observed similar levels of testosterone in recurrent prostate cancer 


 
 
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tissue as compared to androgen-stimulated benign prostate tissue.  (6)  It is also known that in 
response to the low levels of testosterone after ADT, the androgen receptor (AR) has increased 
expression with genetic amplification, potentially allowing AR signaling even with low levels of 
testosterone.  (7,8,9)  Taken together, these data argue that the lowest possible level of 
androgen should be the therapeutic objective in men with CRPC. 
 
Abiraterone acetate and its metabolite abiraterone are selective steroidal inhibitors of CYP17 and 
its associated enzymatic activity.  (10)  The clinical importance of the low androgen levels 
observed despite GNRH agonist therapy is clear from the regular use and benefit of secondary 
hormonal therapies.  For example, ketoconazole does have activity in prostate cancer patients 
with PSA progression despite ADT.  (11,12,13,14)  In this setting, ketoconazole acts as a non-
specific inhibitor of several adrenal enzymes including 17α hydroxylase/C17,20-lyase, with its 
non-specific mechanism requiring the use of glucocorticoids to prevent adrenal insufficiency.  
One analysis correlated the level of adrenal androgens to PSA responses, finding that patients 
with unmeasurable or very low adrenal androgens were less likely to respond to ketoconazole 
than those with higher levels.  (15)  In contrast to the non-specific effects of ketoconazole, 
abiraterone acetate is a targeted CYP 17 inhibitor, with the potential to minimize the adverse 
events seen with ketoconazole. 
 
Over 420 subjects have been exposed to abiraterone acetate in Cougar-sponsored Phase I and II 
open label studies in the United States and the United Kingdom.  In the two Phase III studies, 
COU-AA-301 and COU-AA-302, subjects have been exposed to abiraterone acetate and placebo 
in a 2:1 ratio, and 1:1 ratio, respectively. (16) Overall, abiraterone acetate has been very well 
tolerated with no dose limiting toxicity observed in several trials treating patients with up to 2,000 
mg daily.  Some evidence of secondary mineralocorticoid excess (hypertension, hypokalemia and 
edema) has been observed in the initial studies; it is now recommended that abiraterone acetate 
be given with a low dose of glucocorticoid such as prednisone 5 mg po twice daily to abrogate 
these symptoms, while others have advocated the use of a mineralocorticoid receptor antagonist.  
(17)  Based on the PK profile and the overall toxicity pattern, the recommended Phase II testing 
dose of abiraterone acetate is 1,000 mg daily and this regimen in combination with prednisone of 
5 mg twice a day in the Phase III trials. 
 
Abiraterone Acetate Efficacy Data 
 
The initial human trials of abiraterone acetate were recently reported.  (18)  The main objective of 
these studies was to determine the effect of abiraterone acetate on testosterone levels in both 
normal and medically castrate men.  In single-dose testing, 10 to 800 mg of abiraterone acetate 
was administered.  A repeated-dose cohort of castrated men was also treated with abiraterone 
acetate of 500 or 800 mg by mouth on a daily basis.  Overall, these studies showed that 
testosterone could be suppressed without any significant change in cortisol levels in both castrate 
and non-castrate men.  In castrate men, a single 500 mg dose was able to suppress the 
testosterone to less than 0.14 nmol/L in four of six participants.  Repeated treatment of non-
castrate men with 800 mg daily of abiraterone acetate did achieve testosterone suppression to 
castrate levels, although this wasn’t sustained likely due to compensatory luteinizing hormone 
(LH) hypersecretion. 
 
Ryan et al. have reported on the use of abiraterone acetate in a Phase I trial of men with CRPC.  
(19)  Dose escalation was performed with a daily dose range of 250 to 1,000 mg.  Of 33 treated 
men, 18 (55%) achieved a PSA reduction of > 50% to constitute a PSA response.  At the 
recommended Phase II testing dose of 1,000 mg daily, six (50%) of 12 patients experienced a 
PSA response.  Prior ketoconazole was allowed; of the 19 patients previously treated with 
ketoconazole, 10 (53%) had a PSA response.  These results show promising activity, regardless 
of previous treatment with ketoconazole, and suggest that despite an overlapping mechanism of 
action, abiraterone may be effective when ketoconazole is not. Danila, et al. have described the 
use of abiraterone acetate in men with CRPC who have failed docetaxel chemotherapy. (20)  
Thirty-eight patients were treated with a median baseline PSA of 86 ng/ml, 45% had previously 
received ketoconazole, 32% had one previous line of chemotherapy and 68% had two previous 
lines of chemotherapy.  Thirty-five patients were evaluable at the time of this analysis; at three 


 
 
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months, 14 (40%) of 35 had a PSA response with a reduction of > 50% from their baseline value.  
There was no a clear difference in PSA responses based on prior exposure to ketoconazole. 
 
To better determine the effect of abiraterone on castrate men with prostate cancer, Riggs et al. 
followed the testosterone levels in 12 men receiving abiraterone acetate.  (21)  Using liquid 
chromatography and tandem mass spectrometry detections, ultrasensitive assessments of 
testosterone were obtained.  All men were being treated with GNRH agonists and had a mean 
testosterone of 3.86 ng/dl prior to starting abiraterone acetate.  Ultrasensitive testosterone testing 
revealed that 11 of the 12 patients achieved testosterone levels of < 1 ng/dl over four weekly 
measurements, confirming the ability of abiraterone to quantitatively reduce testosterone in men 
already receiving GNRH agonist therapy. 
 
Investigators at the Royal Marsden Hospital reported on 21 chemotherapy naïve men with CRPC 
who were treated with abiraterone acetate at doses of 250 to 2,000 mg daily.  A PSA reduction of 
> 50% that was maintained for at least three months was observed in 12 (57%) of 21 patients.  Of 
the eight patients with measurable disease, five (62%) achieved a confirmed partial response 
using RECIST criteria.  In addition, eight of 11 patients who required analgesia at baseline for 
pain had a reduction or complete resolution of their pain with abiraterone acetate therapy.  (22) 
 
In summary, abiraterone acetate is a potent and specific inhibitor of testosterone production and 
represents a new generation of ADT.  It has clear activity in men with CRPC as documented in 
several human trials.  An analysis of the data from SWOG-9346 indicates that prostate cancer 
patients who fail to achieve a stable PSA of less than or equal to 4 ng/ml have a poor prognosis.  
The use of abiraterone acetate in this high-risk patient population is rational and compelling.  
While the men eligible for the current study are not necessarily castrate resistant by the traditional 
definition, they are only partially responsive to ADT.  Due to practical considerations, the eligibility 
criteria for the current study are modified slightly from the SWOG-9346 criteria, since the goal of 
the current study is to determine the activity of abiraterone acetate in this population and 
generate data for larger, future trials.  The early use of abiraterone acetate in these men may 
potentiate ADT, prolonging the progression-free survival and postponing the need for more toxic 
chemotherapy. 
 
At the time of S1014 activation, the results of COU-301 had been published.  In a 2:1 ratio, 1,195 
men with castration-resistant prostate cancer and previous docetaxel chemotherapy were treated 
with abiraterone acetate and prednisone versus placebo and prednisone.  There was a 
statistically significant improvement in median overall survival (14.8 versus 10.9 months) favoring 
the abiraterone arm (p<0.001).  There was also improvement in the time to PSA progression, 
progression-free survival and PSA response rate in the abiraterone acetate treatment arm.  (23)  
Abiraterone acetate with prednisone was approved by the FDA in April 2011 for use in metastatic 
castration-resistant prostate cancer following docetaxel. 


 
 
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Inclusion of Minorities: 
 
This study was designed to include minorities, but was not designed to measure differences of 
intervention effects.  The anticipated accrual in the ethnicity/race and sex categories is shown in 
the table below. 
 
Ethnic Category 
Females 
Males 
Total 
Hispanic or Latino 
0 
4 
 
4 
Not Hispanic or Latino 
0 
 
34 
34 
Total Ethnic 
0 
38 
38 
Racial Category 
American Indian or Alaskan Native 
0 
0 
0 
Asian 
0 
1 
1 
Black or African American 
0 
7 
7 
Native Hawaiian or other Pacific Islander 
0 
0 
0 
White 
0 
30 
30 
Racial Category: Total of all Subjects 
0 
38 
38 
 
 
3.0 
DRUG INFORMATION 
 
Investigator’s Brochure 
 
For information regarding Investigator’s Brochures, please refer to SWOG Policy 15. 
 
For this study, abiraterone acetate is investigational and is being provided under an IND held by 
SWOG.  For IND’s filed by SWOG, the protocol serves as the Investigator Brochure for the 
performance of the protocol.  In such instances submission of the protocol to the IRB should 
suffice for providing the IRB with information about the drug.  However, in cases where the IRB 
insists on having the official Investigator Brochure from the company, further information may be 
requested by contacting the SWOG Operations Office at 210/614-8808. 
 
For this study, prednisone is commercially available; therefore, an Investigator Brochure is not 
applicable to this drug.  Information about commercial drugs is publicly available in the 
Physician's Desk Reference (PDR), prescribing information and other resources. 
 
3.1 
Abiraterone Acetate (CB7630) (NSC #748121) (IND-111552) 
 
a. 
PHARMACOLOGY 
 
Abiraterone acetate is converted in vivo to abiraterone, an androgen biosynthesis 
inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase (CYP17). This enzyme is 
expressed in testicular, adrenal and prostatic tumor tissues and is required for 
androgen biosynthesis.  CYP17 catalyzes two sequential reactions: 1) the 
conversion of pregnenolone and progesterone to their 17α-hydroxy derivatives by 
17α-hydroxylase 
activity 
and 
2) 
the 
subsequent 
formation 
of 


 
 
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dehydroepiandrosterone (DHEA) and androstenedione, respectively, by C17, 20 
lyase activity. DHEA and androstenedione are androgens and are precursors of 
testosterone. Inhibition of CYP17 by abiraterone can also result in increased 
mineralocorticoid production by the adrenals. 
  
b. 
PHARMACOKINETICS 
 
Following administration of abiraterone acetate, the pharmacokinetics of 
abiraterone and abiraterone acetate have been studied in healthy subjects and in 
patients with metastatic castrate resistant prostate cancer (CRPC). In vivo, 
abiraterone acetate is converted to abiraterone. In clinical studies, abiraterone 
acetate plasma concentrations were below detectable levels (< 0.2 ng/mL) in > 
99% of the analyzed samples. 
 
1. 
Absorption: Following oral administration of abiraterone acetate to 
patients with metastatic CRPC, the median time to reach maximum 
plasma abiraterone concentrations is 2 hours. Abiraterone accumulation 
is observed at steady-state, with a 2-fold higher exposure (steady-state 
AUC) compared to a single 1,000 mg dose of abiraterone acetate.  At the 
dose of 1,000 mg daily in patients with metastatic CRPC, steady-state 
values (mean ± SD) of Cmax were 226 ± 178 ng/mL and of AUC were 
1173 ± 690 ng.hr/mL.  No major deviation from dose proportionality was 
observed in the dose range of 250 mg to 1,000 mg. 
 
Systemic exposure of abiraterone is increased when abiraterone acetate 
is administered with food. Abiraterone Cmax and AUC0-∞ were 
approximately 7-and 5-fold higher, respectively, when abiraterone 
acetate was administered with a low-fat meal (7% fat, 300 calories) and 
approximately 17- and 10-fold higher, respectively, when abiraterone 
acetate was administered with a high-fat (57% fat, 825 calories) meal. 
Given the normal variation in the content and composition of meals, 
taking abiraterone acetate with meals has the potential to result in 
increased and highly variable exposures. Therefore, no food should be 
consumed for at least two hours before the dose of abiraterone acetate 
is taken and for at least one hour after the dose of abiraterone acetate is 
taken. The tablets should be swallowed whole with water. 
 
2. 
Distribution: Abiraterone is highly bound (>99%) to the human plasma 
proteins, albumin and alpha-1 acid glycoprotein. The apparent steady-
state volume of distribution (mean ± SD) is 19,669 ± 13,358 L. In vitro 
studies show that at clinically relevant concentrations, abiraterone 
acetate and abiraterone are not substrates of P-glycoprotein (P-gp) and 
that abiraterone acetate is an inhibitor of P-gp. No studies have been 
conducted with other transporter proteins. 
 
3. 
Metabolism: Following oral administration of 14C-abiraterone acetate 
as capsules, abiraterone acetate is hydrolyzed to abiraterone (active 
metabolite). The conversion is likely through esterase activity (the 
esterases have not been identified) and is not CYP mediated. The two 
main circulating metabolites of abiraterone in human plasma are 
abiraterone sulphate (inactive) and N-oxide abiraterone sulphate 
(inactive), which account for about 43% of exposure each. CYP3A4 and 
SULT2A1 are the enzymes involved in the formation of N-oxide 
abiraterone sulphate and SULT2A1 is involved in the formation of 
abiraterone sulphate. 
 


 
 
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4. 
Excretion: In patients with metastatic CRPC, the mean terminal half-
life of abiraterone in plasma (mean ± SD) is 12 ± 5 hours. Following oral 
administration of 14C-abiraterone acetate, approximately 88% of the 
radioactive dose is recovered in feces and approximately 5% in urine 
 
The major compounds present in feces are unchanged abiraterone 
acetate and abiraterone (approximately 55% and 22% of the 
administered dose, respectively). 
 
c. 
ADVERSE EFFECTS  
 
1. 
Refer to the package insert or manufacturer's website for the most 
complete and up to date information on contraindications, warnings and 
precautions, and adverse reactions.   
 
Adverse Events with Possible Relationship to Abiraterone Acetate 
 
Likely (>20%) 
Less Likely (≤20%) 
Rare but 
Serious (<3%) 
CARDIAC DISORDERS 
 
Hypertension 
Cardiac failure 
 
Arrhythmias 
 
 
Chest pain or discomfort 
 
GASTROINTESTINAL DISORDERS 
 
Diarrhea 
 
 
Dyspepsia 
 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
Edema 
 
 
Peripheral edema 
 
 
Pitting edema 
 
 
Generalized edema 
 
 
INFECTIONS AND INFESTATIONS 
 
Urinary tract infection 
Urosepsis 
 
Upper respiratory tract 
infection 
 
INVESTIGATIONS 
 
Hypokalemia 
 
 
Hypophosphatemia 
 
 
Increased ALT 
 
 
Increased AST 
 
 
Increased triglycerides 
 
 
Increased total bilirubin 
 
MUSCULOSKELETAL AND CONNECTIVE TISSURE DISORDERS 
Arthritis 
Fractures 
 
Arthralgia 
 
 
Joint swelling 
 
 
Joint stiffness 
 
 
Muscle spasms 
 
 
Musculoskeletal pain 
 
 
Myalgia 
 
 
Musculoskeletal discomfort 
 
 
Musculoskeletal stiffness 
 
 
RENAL AND URINARY DISORDERS 
 
Urinary frequency 
 
 
Nocturia 
 


 
 
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Adverse Events with Possible Relationship to Abiraterone Acetate 
 
Likely (>20%) 
Less Likely (≤20%) 
Rare but 
Serious (<3%) 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
 
Cough 
Non-infectious 
pneumonitis  
VASCULAR DISORDERS 
 
 Hot flash 
 
 
2. 
Warnings and Precautions 
 
Hypertension, Hypokalemia and Fluid Retention Due to Mineralocorticoid 
Excess: Use abiraterone acetate with caution in patients with a history of 
cardiovascular disease.  Abiraterone acetate may cause hypertension, 
hypokalemia, and fluid retention as a consequence of increased 
mineralocorticoid 
levels 
resulting 
from 
CYP17 
inhibition. 
Co-
administration of a corticosteroid suppresses adrenocorticotropic 
hormone (ACTH) drive, resulting in a reduction in the incidence and 
severity of these adverse reactions. Use caution when treating patients 
whose underlying medical conditions might be compromised by 
increases in blood pressure, hypokalemia or fluid retention, e.g., those 
with heart failure, recent myocardial infarction or ventricular arrhythmia. 
The safety of abiraterone acetate in patients with left ventricular ejection 
fraction <50% or NYHA Class III or IV heart failure has not been 
established because these patients were excluded from the randomized 
clinical trial. Monitor patients for hypertension, hypokalemia, and fluid 
retention at least once a month.  
 
Adrenocortical Insufficiency: Adrenocortical insufficiency has been 
reported in clinical trials in patients receiving abiraterone acetate in 
combination with prednisone, following interruption of daily steroids 
and/or with concurrent infection or stress. Use caution and monitor for 
symptoms and signs of adrenocortical insufficiency, particularly if 
patients are withdrawn from prednisone, have prednisone dose 
reductions, or experience unusual stress. Symptoms and signs of 
adrenocortical insufficiency may be masked by adverse reactions 
associated with mineralocorticoid excess seen in patients treated with 
abiraterone acetate. If clinically indicated, perform appropriate tests to 
confirm the diagnosis of adrenocortical insufficiency. Increased dosage 
of corticosteroids may be indicated before, during and after stressful 
situations. 
 
Cardiovascular Adverse Reactions: The majority of arrhythmias were 
Grade 1 or 2. Grade 3-4 arrhythmias occurred at similar rates in the two 
arms. There was one death associated with arrhythmia and one patient 
with sudden death in the abiraterone acetate arm. No patients had 
sudden death or arrhythmia associated with death in the placebo arm. 
Cardiac ischemia or myocardial infarction led to death in 2 patients in the 
placebo arm and 1 death in the abiraterone acetate arm. Cardiac failure 
resulting in death occurred in 1 patient on both arms. 
 
Hepatotoxicity: Drug-associated hepatotoxicity with elevated ALT, AST, 
and total bilirubin has been reported in patients treated with abiraterone 
acetate. Across all clinical trials, liver function test elevations (ALT or 
AST increases of > 5X ULN) were reported in 2.3% of patients who 
received abiraterone acetate, typically during the first 3 months after 
starting treatment. In the Phase III trial, patients whose baseline ALT or 


 
 
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AST were elevated were more likely to experience liver function test 
elevations than those beginning with normal values. When elevations of 
either ALT or AST > 5X ULN, or elevations in bilirubin > 3X ULN were 
observed, abiraterone acetate was withheld or discontinued. In two 
instances marked increases in liver function tests occurred.  These two 
patients with normal baseline hepatic function, experienced ALT or AST 
elevations 15 to 40X ULN and bilirubin elevations 2 to 6 X ULN. Upon 
discontinuation of abiraterone acetate, both patients had normalization of 
their liver function tests and one patient was re-treated with abiraterone 
acetate without recurrence of the elevations. 
 
3. 
Pregnancy and Lactation: Pregnancy Category X. Abiraterone acetate 
is contraindicated in women who are or may become pregnant while 
receiving the drug. If this drug is used during pregnancy, or if the patient 
becomes pregnant while taking this drug, the patient should be apprised 
of the potential hazard to the fetus and the potential risk for pregnancy 
loss. Women of childbearing potential should be advised to avoid 
becoming pregnant during treatment with abiraterone acetate.  It is not 
known if abiraterone acetate is excreted in human milk. Because many 
drugs are excreted in human milk, and because of the potential for 
serious adverse reactions in nursing infants from abiraterone acetate, a 
decision should be made to either discontinue nursing, or discontinue the 
drug taking into account the importance of the drug to the mother. 
 
4. 
Drug Interactions: In vitro studies with human hepatic microsomes 
showed that abiraterone is a strong inhibitor of CYP1A2 and CYP2D6 
and a moderate inhibitor of CYP2C9, CYP2C19 and CYP3A4/5.  In an in 
vivo drug-drug interaction trial, the Cmax and AUC of dextromethorphan 
(CYP2D6 substrate) were increased 2.8- and 2.9-fold, respectively when 
dextromethorphan 30 mg was given with abiraterone acetate 1,000 mg 
daily (plus prednisone 5 mg twice daily). The AUC for dextrorphan, the 
active metabolite of dextromethorphan, increased approximately 1.3 fold.  
For this reason, co-administration of abiraterone acetate with substrates 
of CYP2D6 with a narrow therapeutic index (e.g., thioridazine) should be 
avoided.    
 
Based on in vitro data, abiraterone acetate is a substrate of CYP3A4. 
The 
effects 
of 
strong 
CYP3A4 
inhibitors 
(e.g., 
ketoconazole, 
itraconazole, 
clarithromycin, 
atazanavir, 
nefazodone, 
saquinavir, 
telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) or inducers 
(e.g., 
phenytoin, 
carbamazepine, 
rifampin, 
rifabutin, 
rifapentine, 
phenobarbital) on the pharmacokinetics of abiraterone have not been 
evaluated, in vivo. Avoid or use with caution, strong inhibitors and 
inducers of CYP3A4 during abiraterone acetate. 
 
In a CYP2C8 drug-drug interaction trial in healthy subjects, the AUC of 
pioglitazone (CYP2C8 substrate) was increased by 46% when 
pioglitazone was given together with a single dose of 1,000 mg of 
abiraterone acetate. Therefore, patients should be monitored closely for 
signs of toxicity related to a CYP2C8 substrate with a narrow therapeutic 
index if used concomitantly with abiraterone acetate. 
 
d. 
DOSING & ADMINISTRATION 
 
1. 
Dosing – See Treatment Plan Section 7.0 
 


 
 
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2. 
Abiraterone acetate must be taken on an empty stomach. No food 
should be consumed for at least two hours before the dose of 
abiraterone acetate is taken and for at least one hour after the dose of 
abiraterone acetate is taken. The tablets should be swallowed whole with 
water. Exposure of abiraterone increases up to 10 fold when abiraterone 
acetate is taken with meals. 
 
a. 
STORAGE & STABILITY 
 
Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 
15°C to 30°C (59°F to 86°F) [see USP controlled room 
temperature]. Based on its mechanism of action, abiraterone 
acetate may harm a developing fetus. Therefore, women who 
are pregnant or women who may be pregnant should not handle 
abiraterone acetate without protection, e.g., gloves. 
 
b. 
HOW SUPPLIED  
 
1. 
Abiraterone acetate is supplied as a tablet in 250 mg 
strength.  The tablets are oval, and white to off-white. 
 
2. 
Abiraterone acetate is investigational for this study and 
will be supplied free of charge to patients by Janssen 
Scientific Affairs, LLC for distribution by Biologics.   
 
3. 
Drug Ordering:  Abiraterone acetate may be requested 
by the Principal Investigator (or their authorized 
designee) at each participating institution by completing 
and faxing the Biologics Drug Request for S1014 (see 
S1014 abstract page on the SWOG website) once 
patient has been registered.  Allow 7 business days 
for shipment of drug from receipt of the Biologics 
Drug Request Form.  Form should be faxed to the 
number on the form.  Orders received before 2 p.m. 
EST Monday through Friday will be processed and 
shipped for next business day delivery.  Orders received 
after 2 p.m. EST Monday through Friday will be 
processed and shipped the next business morning.  
Shipments will be sent via Federal Express for Priority 
Overnight delivery.  Biologics will be closed the following 
holidays:  New Years Eve, New Years Day, Memorial 
Day, Independence Day, Labor Day, Thanksgiving, 
Thanksgiving Friday, Christmas Eve and Christmas Day.  
The abiraterone acetate to be supplied for this protocol 
is intended for clinical trial use only. 
 
Initial Shipments: Once a patient is registered, the site 
will fax a completed Drug Request Form to Biologics at 
919-256-0794. Upon receipt of completed and faxed 
Drug Request Form, Biologics Inc. will: 
 
• 
Place a call or email to the site confirming the Drug 
Request Form was received, while providing the 
estimated day and time of arrival for the study drug.  
At this time, Biologics will confirm the patient’s dose 
for the first three - 28 day cycles and confirm the 
Drug Request Form is completed. 
 
• 
Prepare an initial shipment supply for the patient’s 
first three - 28 day cycles (based on a dose provided 


 
 
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by the registration/site [1,000 mg]). Shipments will 
include 3 bottles of study drug to complete the 28 
day cycle at a dose of 1,000 mg PO QD x 28 
days. Drug supply will be dispensed in a bottle with 
patient specific labeling. Each bottle will contain 120 
tablets of study drug. 
 
Follow up Calendar. Biologics will contact the site 
approximately 14 days prior to the next cycle start date 
to arrange the next shipment. 
 
Subsequent Shipments: Biologics will contact the site 
approximately 14 days prior to the next cycle due date to 
request a completed Drug Request Form and the next 
cycle start date to arrange the next shipment. 
 
Upon receipt of completed and faxed Drug Request 
Form, Biologics Inc. will 
 
• 
Place a call or email to the site confirming the Drug 
Request Form was received, while providing the 
estimated day and time of arrival for the study drug.  
At this time, Biologics will confirm the patient’s dose 
and number of cycles requested.  
 
• 
Prepare the subsequent shipment supply for the 
patient for the number of cycles requested, based on 
the dose provided by the site.  Shipments will 
include 3 bottles of study drug to cover the next 3 
cycles.  Drug supply for each cycle will be dispensed 
in a bottle with patient specific labeling.  Each bottle 
will contain 120 tablets of study drug based on the 
patient’s current dose. Date of next shipment is 
entered into a Follow up Calendar.  Biologics will 
contact the site approximately 14 days prior to the 
next cycle start date to arrange the next shipment. 
• 
Process and ship authorized and completed orders 
“same day” of order receipt if received before 2:00 
p.m. E.T Monday through Friday. Authorized and 
completed orders received after 2:00 pm E.T. 
Monday through Friday will be processed and 
shipped the next business morning.  
 
All drug orders are shipped via FedEx for Priority 
Overnight delivery. Study Drug is shipped in a 
Biologics, Inc. branded box with appropriate ice to 
maintain temperature stability.  Each shipment will 
include a temperature monitoring device with 
instructions for interpretation by recipient.  This will 
ensure that the temperature was maintained during 
transit.  Enclosed will be a packing slip that includes 
the quantity of drug provided with a section to be 
completed once received by the site coordinator. 
This section includes confirmation of drug receipt, 
verification of package contents, and instruction to 
fax the completed packing slip to Biologics. 
 
• 
Each shipment includes a patient label on the Ziploc 
bags with the following information: 
o 
Study number and Date Dispensed 


 
 
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o 
IND Caution statement and/or local regulatory 
statements ‘Investigational Drug’ 
o 
Drug Identification, Lot number, Expiration 
o 
Subject ID number 
o 
Subject Initials 
o 
Storage conditions 
o 
Dosing Instructions 
 
Packages are tracked by Biologics, Inc. until 
confirmed delivered and delivery exceptions are 
managed with the highest level of urgency to ensure 
therapy start date adherence.  Packing slips with the 
shipment tracking number included will be faxed to 
the designated site coordinator for all shipments. 
 
Once study drug is received at the clinical trial site: 
 
• 
The 
designated 
site 
coordinator 
validates 
contents 
of 
package 
matches 
information 
provided on packing slip, signs off on the 
packing slip, and faxes completed form to 
Biologics 
to 
validate 
shipment 
has 
been 
received and is accurate.  
 
The order transaction is completed by Biologics, 
Inc. by entering the receipt confirmation into the 
CTS database and placing the signed packing 
slip in the study file. 
 
Year 1 Example of Biologics Follow up Calendar 
and Shipment Schedule (to continue for 3 years) 
 
Cycle(s) 
Months 
1-3 
Months 
4-6 
Months 
7-9 
Months 
10-12 
Follow up 
Date by 
Biologics 
(call site) 
n/a 
14 Days 
prior to 
Start of 
Cycle 4 
(Day 
70) 
14 Days 
prior to 
Start of 
Cycle 7 
(Day 
182) 
14 Days 
prior to 
Start of 
Cycle 10 
(Day 
266) 
Next 
Shipment 
Due Date 
n/a 
Month 6 
Month 9 
Month 12 
 
4. 
Drug Handling and Accountability  
 
a. 
The 
investigator, 
or 
a 
responsible 
party 
designated by the investigator, must maintain a 
careful record of the receipt, disposition, and 
return or disposal of all drug received from the 
supplier using the NCI Drug Accountability 
Record 
Form 
(DARF) 
available 
at 
http://ctep.cancer.gov. 
 
b. 
Electronic logs are allowed as long as a print 
version of the log process is the exact same 
appearance as the current NCI DARF.  
 


 
 
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5. 
Drug Returns: Unused drug supplies should NOT be 
returned.  Unused drug should be disposed of per local 
institutional guidelines. 
 
6. 
Questions about drug orders, transfers, returns, or 
accountability should be addressed to Karl Buer at 
Biologics, 
Inc. 
(800/693-4906 
or 
kbuer@biologicstoday.com). 
 
3.2 
Prednisone (NSC-10023) 
 
a. 
DESCRIPTION 
 
Prednisone is a glucocorticoid which is rapidly absorbed from the GI tract. 
 
b. 
TOXICOLOGY 
 
Human Toxicology:  Possible adverse effects associated with the use of 
prednisone are:  fluid and electrolyte disturbances, congestive heart failure in 
susceptible persons, hypertension, euphoria, personality changes, insomnia, 
mood swings, depression, exacerbation of infection (e.g., tuberculosis), 
exacerbation or symptoms of diabetes, psychosis, muscle weakness, 
osteoporosis, vertebral compression fractures, pancreatitis, esophagitis, peptic 
ulcer disease, dermatologic disturbances, convulsions, vertigo and headache, 
endocrine abnormalities, ophthalmic changes, and metabolic changes.  Some 
patients have experienced itching and other allergic, anaphylactic or other 
hypersensitivity reactions.  Withdrawal from prolonged therapy may result in 
symptoms of adrenal insufficiency including fever, myalgia and arthralgia.  
Phenytoin, phenobarbitol, and ephedrine enhance metabolic clearance of 
corticosteroids. 
 
Corticosteroids should be used cautiously in patients with hypothyroidism, 
cirrhosis, ocular herpes simplex, existing emotional instability or psychotic 
tendencies, 
nonspecific 
ulcerative 
colitis, 
diverticulitis, 
fresh 
intestinal 
anastomoses, 
peptic 
ulcer 
disease, 
renal 
insufficiency, 
hypertension, 
osteoporosis and myasthenia gravis.  Immunization procedures (especially 
smallpox vaccination) should not be undertaken in patients on corticosteroids. 
 
c. 
PHARMACOLOGY 
 
Pharmacokinetics:  Natural and synthetic glucocorticoids are readily and 
completely absorbed from the GI tract.  Prednisone is slightly soluble in water.  
Glucocorticoids have salt-retaining properties.  The anti-inflammatory property of 
this drug is due to a down-regulation of the body's immune system and as a 
consequence it can suppress the body's response to viral as well as bacterial 
infections. 
 
Formulation:  Prednisone is available in 2.5 mg, 5 mg, 10 mg, 20 mg and 50 mg 
tablets. 
 
Storage and Stability:  Prednisone should be stored at room temperature. 
 
Administration:  Prednisone is administered orally. 
 
Supplier:  Prednisone is commercially available and should be purchased by third 
party.  Prednisone will not be supplied by the NCI. 
 
Please refer to the Physician Desk Reference and package insert for complete 
information. 


 
 
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4.0 
STAGING CRITERIA 
 
Distant metastasis (M) 
 
M1: 
Distant metastasis  
 
NOTE:  Regional lymph node metastasis by itself is insufficient for the classification of M1 
disease. 
 
5.0 
ELIGIBILITY CRITERIA 
 
Each of the criteria in the following section must be met in order for a patient to be considered eligible for 
registration.  Use the spaces provided to confirm a patient's eligibility.  For each criterion requiring test 
results and dates, please record this information on the S1014 Prestudy Form and submit to the Data 
Operations Center in Seattle (see Section 14.0).  Any potential eligibility issues should be addressed to 
the Data Operations Center in Seattle at 206/652-2267 prior to registration. 
 
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 2 weeks later would be 
considered Day 14.  This allows for efficient patient scheduling without exceeding the guidelines.  
If Day 14, 28, 42, or 56 falls on a weekend or holiday, the limit may be extended to the next working 
day. 
 
5.1 
Disease Related Criteria 
 
a. 
All patients must have a histologically or cytologically proven diagnosis of 
adenocarcinoma of the prostate.  Small cell or neuroendocrine prostate cancer is 
not allowed.  All patients must have had metastatic (M1) (see Section 4.0) 
disease as evidenced by soft tissue and/or bony metastases at the time of 
initiation of androgen deprivation therapy (ADT).  Patients must have at least one 
of the following at the time they started androgen deprivation therapy: 
 
(1) 
Visceral disease (liver, lung, other viscera),   
(2) 
Bone metastases to sites in either the axial (spine, pelvis, ribs, skull) 
and/or the appendicular (clavicle, humerus, femur) skeleton, 
(3) 
Distant lymph node disease (e.g. above the aortic bifurcation, etc.). 
 
b. 
Patients must have a Zubrod performance status of 0 - 2 (see Section 10.3). 
 
c. 
All patients must be receiving androgen deprivation therapy (e.g., GNRH agonist 
with or without antiandrogen) prior to entering this study.  Degarelix, a FDA-
approved GNRH antagonist, is an acceptable form of androgen deprivation 
therapy. Bilateral surgical orchiectomy is also acceptable. 
 
d. 
Only patients with a suboptimal response to initial androgen deprivation therapy 
(ADT) induction, with a PSA of > 4 ng/ml between 6-12 months from starting ADT 
for metastatic disease, will be eligible.   Documentation of failure to achieve this 
PSA of ≤ 4 ng/ml must be within 28 days of registration. The PSA must be 
obtained after any applicable antiandrogen washout period.  
 
If the PSA is declining or stable (defined as a PSA rise ≤ 0.1 ng/ml from nadir) 
and the patient is on an antiandrogen, they must remain on the antiandrogen 
(see Section 7.3).  Patients with stable or declining PSA who have had previous 
antiandrogen exposure, but are not taking an antiandrogen at the time of 
registration, must wait at least 6 weeks from the last antiandrogen dose before 


 
 
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registration and still demonstrate a stable or falling PSA which is > 4 ng/ml by 
month 12, in order to be eligible. 
 
If the PSA is rising and they are on an antiandrogen, formal antiandrogen 
washout must be performed (4 weeks for flutamide and 6 weeks for bicalutamide 
and nilutamide with no evidence of a falling PSA after washout).  
 
e. 
Patients who have any measurable disease must have it assessed by an 
abdominal/pelvic CT within 28 days prior to registration. All non-measurable 
disease must be assessed by a bone scan within 42 days prior to registration.  
All disease must be assessed and documented on the Baseline Tumor 
Assessment Form. 
 
f. 
Patients with a history of prior neoadjuvant or adjuvant GNRH agonist/antagonist 
therapy (related to previous surgery or radiation) are eligible provided they 
finished this therapy at least two years prior to registration.  Prior use of 
finasteride or dutasteride is allowed as long as it is discontinued at least 6 weeks 
prior to registration.  Prior enrollment to S0925 (either arm) is not exclusionary.   
 
g. 
Patients with a history of brain metastases or who currently have treated or 
untreated brain metastases are not eligible. Patients with clinical evidence of 
brain metastases must have a brain CT or MRI negative for metastatic disease 
within 56 days prior to registration 
 
h. 
Patients must not have received any prior cytotoxic chemotherapy or 
radiopharmaceuticals for prostate cancer. Previous ketoconazole therapy for the 
treatment of prostate cancer is not allowed.  Patients requiring more than 10 mg 
a day of prednisone for another medical indication are not eligible. Patients must 
not have received any prior Provenge. 
 
5.2 
Prior/Concurrent Therapy Criteria 
 
a. 
Patients must not have received any prior cytotoxic chemotherapy or 
radiopharmaceuticals for prostate cancer. Previous ketoconazole therapy for the 
treatment of prostate cancer is not allowed.  Patients requiring more than 10 mg 
a day of prednisone for another medical indication are not eligible. Patients must 
not have received any prior Provenge. 
 
b. 
Patients may have received prior radiation therapy or surgery.  However, at least 
28 days must have elapsed since completion of radiation therapy or surgery and 
patient must have recovered from all side effects. 
 
c. 
Patients must not be planning to receive any concurrent cytotoxic chemotherapy, 
surgery, or radiation therapy during protocol treatment.  Hormonal-acting agents 
(including diethylstilbestrol/DES, aldosterone, PC-SPES, and spironolactone) are 
forbidden during the trial and must be stopped prior to registration.  No washout 
period will be required for any of these agents.  However, any investigational 
products must be stopped at least 28 days (4 week washout) prior to registration. 
 
5.3 
Clinical/Laboratory Criteria 
 
a. 
Patient must have a testosterone value of < 50 ng/dl obtained within 28 days 
prior to registration. 
 
b. 
Patients must have absolute neutrophil count (ANC) ≥ 1,500/mcL, platelet count 
≥ 100,000/mcL and hemoglobin ≥ 10 g/dl obtained within 28 days prior to 
registration. 
 


 
 
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c. 
Patients must have serum creatinine ≤ 1.5 x the institutional upper limit of normal 
(ULN) or a calculated creatinine clearance of ≥ 60 ml/min obtained within 28 days 
prior to registration. 
 
Calculated creatinine clearance = (140 - age) x wt (kg) 
72 x creatinine (mg/dl) 
 
d. 
Patients must have a bilirubin ≤ 1.5 x ULN (unless documented Gilbert's 
disease), SGOT (AST) and SGPT (ALT) < 1.5 x ULN obtained within 28 days 
prior to registration. 
 
e. 
Patients must have potassium ≥ 3.5 mmol/L obtained within 28 days prior to 
registration. 
 
f. 
Patients must be able to take oral medication without crushing, dissolving or 
chewing tablets.  Patients must not have a history of gastrointestinal disorders 
(medical disorders or extensive surgery) that may interfere with the absorption of 
abiraterone acetate. 
 
g. 
Patients with active or symptomatic viral hepatitis or chronic liver disease are not 
eligible.  Patients must not have moderate (Child-Pugh B) or severe (Child-Pugh 
C) hepatic impairment (see Appendix 18.5). 
 
h. 
Patients must have well controlled blood pressure defined as a systolic blood 
pressure < 160 mmHg and diastolic blood pressure < 95 mmHg at the time of the 
screening visit.  Patients with a history of hypertension are eligible provided blood 
pressure is controlled within these parameters with anti-hypertensive treatment. 
 
i. 
Patients with a history of New York Heart Association Class III and IV heart 
failure (see Appendix 18.2) or a known left ventricular ejection fraction (LVEF) of 
< 50% are not eligible. 
 
j. 
Patients must not have known allergies, hypersensitivity, or intolerance to 
abiraterone acetate, prednisone or their excipients. 
 
k. 
No other prior malignancy is allowed except for the following: adequately treated 
basal cell or squamous cell skin cancer, adequately treated Stage I or II cancer 
from which the patient is currently in complete remission, or any other cancer 
from which the patient has been disease-free for 5 years. 
 
l. 
Patients who have partners of child-bearing potential must be willing to use a 
method of birth control with adequate barrier protection during the study and for 
one week after the last study drug administration. 
 
5.4 
Regulatory Criteria 
 
a. 
All patients must be informed of the investigational nature of this study and must 
sign and give written informed consent in accordance with institutional and 
federal guidelines. 
 
b. 
As a part of the OPEN registration process (see Section 13.3 for OPEN access 
instructions) the treating institution's identity is provided in order to ensure that 
the current (within 365 days) date of institutional review board approval for this 
study has been entered in the system. 
 
 
6.0 
STRATIFICATION FACTORS 
 
There are no stratification factors for this study. 
 


 
 
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7.0 
TREATMENT PLAN 
 
For treatment or dose modification related questions, please contact Dr. Thomas Flaig at 
303/724-3808 or Dr. Maha Hussain at 734/936-8906.  For dosing principles or questions, please 
consult the SWOG Policy #38 "Dosing Principles for Patients on Clinical Trials" at http://swog.org 
(then click on "Policies and Manuals" under the "Visitors" menu and choose Policy #38). 
 
7.1 
Good Medical Practice 
 
The following tests (and/or assessments) are recommended within 28 days prior to 
registration in accordance with Good Medical Practice.  Results of these tests do not 
determine eligibility and minor deviations from normal limits would be acceptable if they 
do not affect patient safety in the clinical judgment of the treating physician.  If there are 
significant deviations in these tests/assessments that could impact on patient safety, it is 
highly recommended that the registering investigator discuss the patient with the Study 
Coordinator prior to patient registration.   
 
Pre-study tests for good medical practice include the following: 
 
a. 
Alkaline phosphatase obtained, 
 
Patients must have recovered from major infections.  In the opinion of the 
investigator the patient must not have any significant active concurrent medical 
conditions which would exclude protocol treatment. 
 
b. 
Patients must not have a history of pituitary or adrenal dysfunction. 
 
c. 
Patients should not have any medical condition, which in the opinion of the 
investigator places the patient at undue risk of potentially serious complications 
while on therapy. These would include: untreated diabetes mellitus, infection, or 
concurrent medications that alter cardiac conduction. 
 
7.2 
Treatment Schedule 
 
 
AGENT 
DOSE 
ROUTE 
DAYS 
DURATION 
 
Abiraterone 
1,000 mg 
PO 
Daily (On an 
Until disease 
acetate 
(4 tablets) 
 
 
empty at least 
progression 
 
 
 
 
 
2 hours after 
 
 
 
 
 
 
and 1 hour 
 
 
 
 
 
before eating.) 
 
Prednisone 
5 mg 
 
PO 
 
5 mg twice 
Until disease 
 
 
 
 
 
daily 
progression 
 
 
Abiraterone acetate:  Four 250 mg tablets (1,000 mg) must be taken orally on an empty 
stomach at least 2 hours after and 1 hour before a meal any time up to 10:00 p.m. every 
day.  Abiraterone acetate may be taken with prednisone.  A cycle of treatment for this 
study is 28 days.   
 
Patients will continue treatment until disease progression or other reason for 
discontinuation of protocol treatment (see Section 7.5). 


 
 
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7.3 
Prior Anti-Androgen Use 
 
 
Patients will have received androgen blockade with GNRH agonist (goserelin 
acetate or leuprolide acetate) or a GNRH antagonist (Degarelix) per the treating 
physician and this will be given continuously throughout protocol treatment.  
Bilateral surgical orchiectomy is also acceptable. 
 
Since stopping an antiandrogen may impact the primary endpoint of the study, there are 
specific instructions about the use of antiandrogens for patients registered with a stable 
or declining PSA (≤ 0.1 ng/ml rise over nadir) and taking antiandrogen therapy (e.g. 
flutamide, bicalutamide, nilutamide) at the time of registration.  These patients must be 
willing to continue on this therapy without washout for the duration of protocol treatment.  
 
7.4 
Intake Calendar 
 
Abiraterone acetate and prednisone compliance will be recorded by patients on the 
Intake Calendar (see Appendix 18.3).  Institutional CRAs will review and ascertain patient 
adherence with protocol therapy at the end of treatment for each cycle.  Calendar should 
be kept in the patient's clinic chart.  Note that the Intake Calendar is provided only as a 
tool for tracking compliance.  Sites may utilize institutional pill diaries or other source 
documentation in place of the Intake Calendar at the discretion of the treating physician. 
 
7.5 
Concomitant Medications 
 
The use of supportive care medications is allowed according to institutional standards.  
GNRH agonist (e.g. goserelin acetate or leuprolide) or antagonist (Degarelix) must be 
continued throughout the study and are considered a standard of care treatment for this 
patient population. 
 
Several medications are specifically allowed.  Conventional multi-vitamins are allowed.  
Additional glucocorticoid use, beyond prednisone 5 mg twice daily, is allowed as deemed 
medically necessary. Bisphosphonates and denosumab are allowed, provided this 
therapy was started prior to registration.  Transfusions and hematologic growth factors 
are allowed in accordance with institutional guidelines.  Antiandrogens (e.g. flutamide, 
bicalutamide, and nilutamide) are to be continued in certain circumstances (see Section 
5.1d for details).  Since the cessation of an antiandrogen may impact PSA, antiandrogens 
are not to be stopped while on protocol.  If the antiandrogen needs to be stopped for 
safety or other reasons, patient must be taken off protocol treatment. 
 
Several medications are specifically disallowed.  Five-alpha reductase inhibitors 
(e.g. finasteride and dutasteride) are not permitted.  Other excluded therapies 
include ketoconazole, diethylstilbestrol/DES, aldosterone, spironolactone, and PC-
SPES.  Other excluded treatments include chemotherapy, immunotherapy, and 
radiopharmaceuticals or any other therapy intended to treat prostate cancer. In 
vitro studies with human hepatic microsomes showed that abiraterone is a strong 
inhibitor of CYP1A2 and CYP2D6 and a moderate inhibitor of CYP2C9, CYP2C19 
and CYP3A4/5.  Avoid co-administration of abiraterone acetate with substrates of 
CYP2D6 with a narrow therapeutic index (e.g., thioridazine). If alternative 
treatments cannot be used, exercise caution and consider a dose reduction of the 
concomitant CYP2D6 substrate drug.  Based on in vitro data, abiraterone acetate is 
a substrate of CYP3A4. The effects of strong CYP3A4 inhibitors (e.g., 
ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, 
telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) or inducers (e.g., 
phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital) on the 
pharmacokinetics of abiraterone have not been evaluated, in vivo. Avoid or use 
with caution, strong inhibitors and inducers of CYP3A4 during abiraterone acetate 
treatment. 


 
 
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Please also see Appendix 18.4 for more details regarding specific drugs that may interact 
with abiraterone acetate in reference to these guidelines. 
 
7.6 
Criteria for Removal from Protocol Treatment 
 
 
a. 
Progression of disease or symptomatic deterioration (as defined in Sections 
10.1-10.2). 
 
b. 
Unacceptable toxicity. 
 
c. 
The patient may withdraw from the study at any time for any reason. 
 
d. 
Delay of greater than four weeks beyond the planned abiraterone acetate 
treatment date or the requirement of more than two dose reductions of 
abiraterone acetate. 
 
e. 
For the subset of patients taking an antiandrogen at baseline and continuing it 
during protocol treatment (see Section 5.1d), these patients must be taken off 
protocol treatment if they stop taking the antiandrogen. 
 
NOTE:  Patients are not to be removed from protocol treatment for PSA progression only.  
In order to be considered a "responder" with regard to the primary endpoint, a patient will 
need to achieve a confirmed PSA of < 0.2 ng/ml by 12 months.  However, a non-
responding patient who is judged to have a clinical benefit from the protocol treatment 
may continue to receive treatment until one of the specific criteria above are reached.  In 
addition, for the subset of patients taking an antiandrogen at registration and continuing 
this treatment (see Section 5.1d), the antiandrogen cannot be discontinued while on the 
protocol, as this may affect the PSA kinetics. 
 
7.7 
Discontinuation of Treatment 
 
All reasons for discontinuation of treatment must be documented in the study forms. 
 
7.8 
Follow Up Period 
 
 
8.0 
DOSAGE MODIFICATIONS 
 
8.1 
NCI Common Terminology Criteria for Adverse Events 
 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) 
Version 4.0 for toxicity and Serious Adverse Event reporting.  A copy of the CTCAE 
Version 4.0 can be downloaded from the CTEP home page (http://ctep.cancer.gov).  All 
appropriate treatment areas should have access to a copy of the CTCAE Version 4.0. 
 
8.2 
Dose Levels of Study Drugs  
 
Dose levels are defined below: 
 
 Dose Level 
Abiraterone acetate 
Prednisone 
 0      
1,000 mg daily 
5 mg twice daily  
-1 
750 mg daily 
5 mg twice daily 
-2 
500 mg daily  
5 mg twice daily 
 


 
 
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8.3 
Abiraterone Acetate Dose Modifications 
 
An adverse event, using the common terminology definition, is any unfavorable and 
unintended sign (including an abnormal laboratory finding), symptom, or disease 
temporally associated with the use of a medical treatment that may or may not be related 
to that treatment.  A dose reduction will be pursued for any serious adverse event, 
defined as any Grade 4 toxicity and also for any Grade 3 toxicity that is believed to 
potentially impact the safety of the participant.  The dose of abiraterone will not be re-
escalated once a dose reduction has occurred.  Abiraterone will be held and the subjects 
followed until resolution of any Grade 3 or 4 adverse event to ≤ Grade 1.  Asymptomatic 
laboratory abnormalities would not be considered a serious adverse event unless the 
investigator believes it may potentially impact the participant’s safety or unless it is 
specifically addressed separately in the protocol (e.g. hypokalemia and liver test 
abnormalities). 
 
Due to the known side effect of hypokalemia, oral replacement of potassium is to be 
started with grade 1 hypokalemia.  With Grade 3 or 4 hypokalemia, abiraterone acetate is 
to be held until it resolves to ≤ Grade 1 and IV potassium replacement is to be given with 
appropriate monitoring.  
 
For patients who develop hepatotoxicity during treatment with abiraterone acetate (ALT 
and/or AST greater than 5X ULN or total bilirubin greater than 3X ULN), interrupt 
treatment with abiraterone acetate.  Treatment may be restarted at a reduced dose of 
750 mg once daily (dose level -1) following return of liver function tests to the patient’s 
baseline or to AST and ALT less than or equal to 2.5X ULN and total bilirubin less than or 
equal to 1.5X ULN. For patients who resume treatment, monitor serum transaminases 
and bilirubin at a minimum of every two weeks for three months and monthly thereafter.  
If hepatotoxicity recurs at the dose of 750 mg once daily, re-treatment may be restarted 
at a reduced dose of 500 mg once daily (dose level -2) following return of liver function 
tests to the patient’s baseline or to AST and ALT less than or equal to 2.5X ULN and total 
bilirubin less than or equal to 1.5X ULN. 
 
If hepatotoxicity recurs at the reduced dose of 500 mg once daily, discontinue treatment 
with abiraterone acetate. The safety of abiraterone acetate re-treatment of patients who 
develop AST or ALT greater than or equal to 20X ULN and/or bilirubin greater than or 
equal to 10X ULN is unknown and patients who develop liver function test abnormalities 
to this degree will be removed from the study.  
 
8.4 
Prednisone Dose Modifications 
 
Prednisone is included in this regimen primarily as a safety medication to reduce the 
potential incidence of mineralocorticoid excess from abiraterone acetate.  For this reason, 
the prednisone cannot be dose reduced or held without holding the abiraterone acetate.  
If Grade 3 or 4 toxicity develops which is known to be related to prednisone (e.g. 
hyperglycemia) and this is believed to potentially impact the safety of participation, both 
prednisone. 
 
8.5 
Dose Modification Contacts 
 
For treatment or dose modification related questions, please contact Dr. Thomas Flaig at 
303/724-3808 or Dr. Maha Hussain at 734/936-8906. 
 
8.6 
Adverse Event Reporting 
 
Toxicities (including suspected reactions) that meet the expedited reporting criteria as 
outlined in Section 16.0 of the protocol must be reported to the Operations Office, Study 
Coordinator, the NCI via CTEP-AERS, and to the IRB per local IRB requirements. 


 
 
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9.0 
STUDY CALENDAR 
 
9.1 
Calendar 
¶ 
Ω 
Σ 
£ 
  
  
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
F/U 
F/U 
REQUIRED 
STUDIES 
PRE 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Prior 
to 
After 
  
STUDY 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
Prog 
Prog 
PHYSICAL 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
History & 
Physical Exam 
X 
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
X 
Weight and 
Performance 
Status 
X 
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
  
X 
Blood Pressure  
X 
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
  
Disease 
Assessment ≠ 
X 
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
  
  
  
  
Toxicity Notation   
π 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
  
  
  
X 
Adverse Event 
Assessment  π 
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
LABORATORY 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Serum PSA  * 
X* 
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
X 
Serum 
Testosterone 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
CBC/Differential/
Platelets/Hemogl
obin  
X 
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
  
X 
Creatinine  
X 
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
  
X 
Potassium  
X 
X 
  
  
  
X 
  
  
  
X 
  
  
  
X 
  
  
  
  
X 
Bilirubin  
X 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
  
  
  
X 
Albumin 
X 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
  
  
  
X 
SGOT and SGPT  
X 
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
X 
  
  
  
  
X 
Alkaline 
Phosphatase β 
 X 
 X 
  
 X 
  
 X 
  
 X 
  
 X 
  
 X 
  
 X 
  
  
  
  
 X 
Calendar continued on next page.  Click here for footnotes. 


 
 
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¶ 
Ω 
Σ 
£ 
  
  
Cycle 1 
Cycle 2 
Cycle 3 
Cycle 4 
F/U 
F/U 
REQUIRED 
STUDIES 
PRE 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Wk 
Prior 
to 
After 
  
STUDY 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
15 
16 
Prog 
Prog 
X-RAYS AND 
SCANS 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
CT or MRI of 
Brain § 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
CT of Abdomen 
& Pelvis    ≠  
X 
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
  
  
X 
  
Bone Scan  ≠  
X 
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
  
  
X 
  
TREATMENT 
(see Section 
7.0) 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Abiraterone 
acetate  ¥ 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
Prednisone ¥ 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
  
NOTE:  Forms are found on the protocol abstract page of the SWOG website (www.swog.org).  Forms submission guidelines 
are found in Section 14.0. 
Footnotes: 
≠ Radiographic assessment will be done every 12 weeks by the same method used to document metastatic disease at baseline and as clinically indicated.  
REMEMBER, PSA RESPONSE SHOULD BE CONFIRMED BY A SECOND PSA DETERMINATION AT LEAST 4 WEEKS AFTER A PSA RESPONSE 
HAS BEEN NOTED. 
§ Only if clinically indicated (see Section 5.2g). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
¥ Treatment will be given daily and will continue until disease progression or other reason for discontinuation of protocol treatment see Section 7.5). 
¶ Laboratory assessments and exam do not need to be repeated on Day 1, Week 1 if the prestudy laboratory assessments and exam was done within 7 days. 
Ω Protocol treatment and assessment parameters will continue at these intervals (monthly exam and laboratory assessment and radiographic assessment 
every 6 months) until off protocol treatment (see Section 7.5). Scans may be performed more frequently than every 6 months at the investigator’s discretion 
or with any signs or symptoms of progression. 
Σ Once off protocol treatment and prior to progression, physical exams, x-rays, scans and PSA for disease assessment should be performed at least every 6 
months or earlier as clinically indicated to assess patient for progression for up to 3 years from registration. 
£ After disease progression, follow-up will occur at the discretion of the treating investigator.  Survival status will be assessed for up to 3 years from 
registration. 
* See Section 5.1d 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
π A toxicity notation is required whenever a laboratory assessment is done (every 2 weeks for the first 3 months, then monthly) and at the last study visit.  An 
adverse event assessment with a physical examination must be done monthly.  Patients who experience adverse events of ≥ Grade 3 severity must be 
followed until resolution or stabilization of the adverse event. 
β Result of this test does not determine eligibility, but is recommended prior to registration in accordance with Good Medical Practice (see Section 7.1). 
 


 
 
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10.0 
CRITERIA FOR EVALUATION AND ENDPOINT DEFINITIONS 
 
10.1 
Progression Criteria 
 
PSA assessments will not be used to determine progression.  One or more of the 
following must occur:  Unequivocal progression of disease in the opinion of the treating 
physician (an explanation must be provided).  Progressive disease as defined by RECIST 
1.1 or the prostate cancer working group bone scan progression criteria as described 
below.  Death due to disease without documented progression and without symptomatic 
deterioration (see Section 10.2) will be considered progression. 
 
When bone scan progression is the only indicator of progression, at least 2 new bone 
scan lesions must be observed, compared to study entry exam.  When progression on 
bone scan is observed at the first scheduled exam (at 12 weeks of protocol treatment), 
without clear soft tissue or symptomatic progression, this finding should be confirmed at 
least 6 weeks later with the development of additional new lesions, to exclude flare 
phenomenon (for a total of 4 or more lesions on the confirmatory bone scan).  When 
progression occurs on bone scans beyond the first assessment point (at 12 weeks of 
protocol treatment), the appearance of 2 or more new lesions compared to baseline is 
still required.  A confirmatory bone scan should generally be done in this situation at least 
6 weeks later, unless there is the appearance of multiple new lesions in which case 
confirmation is not required, based on investigator assessment.  If a confirmatory scan is 
not planned, the SWOG Study Coordinator should be contacted to discuss. (23)  An 
increase in size or intensity of a known lesion is not sufficient for progression criteria.  
Subjects will also be deemed to have progressed if they require surgery to the bone, 
radiation therapy to the bone, or any other local bone-directed treatment.  Progression 
will be calculated from the time of the first bone scan with a new metastatic lesion, not the 
confirmatory scan. 
 
10.2 
Symptomatic Deterioration 
 
Global deterioration of health status requiring discontinuation of treatment without 
objective evidence of progression.  
 
Notes:  (1) In cases for which initial flare reaction is possible (hypercalcemia, increased 
bone pain, erythema of skin lesions), either symptoms must persist beyond 4 weeks or 
there must be additional evidence of progression.  (2)  Lesions that appear to increase in 
size due to presence of necrotic tissue will not be considered to have progressed. (3)  For 
bone disease documented on bone scan only, increased uptake does not constitute 
unequivocal progression.  (4)  Appearance or worsening of pleural effusions does not 
constitute unequivocal progression unless cytologically proven of neoplastic origin. 
 
10.3 
Performance Status 
 
Patients will be graded according to the Zubrod Performance Status Scale. 
 
POINT 
DESCRIPTION 
 
0 
Fully active, able to carry on all pre-disease performance without 
restriction. 
 
1 
Restricted in physically strenuous activity but ambulatory and 
able to carry out work of a light or sedentary nature, e.g., light 
housework, office work.   
 
2 
Ambulatory and capable of self-care but unable to carry out any 
work activities; up and about more than 50% of waking hours. 
 
 


 
 
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3 
Capable of limited self-care, confined to bed or chair more than 
50% of waking hours.   
 
4 
Completely disabled; cannot carry on any self-care; totally 
confined to bed or chair.   
 
10.4 
Time to Treatment Failure   
 
From date of registration to date of first documentation of progression or symptomatic 
deterioration (as defined above), early discontinuation of treatment, or death due to any 
cause.  Patients last known not to have failed treatment are censored at the date of last 
contact.   
 
10.5 
Time to Death   
 
From date of registration to date of death due to any cause.  Patients last known to be 
alive are censored at date of last contact. 
 
10.6 
Undetectable PSA 
 
Undetectable PSA is the primary endpoint and defined as a PSA level of ≤ 0.2 ng/ml, 
confirmed by a second measurement with a PSA ≤ 0.2 ng/ml at least 4 weeks later, 
without any evidence for progression.  The primary endpoint will be assessed on an 
ongoing basis for the first year on study.  Patients not responding within the first year on 
study will be classified as non-responders for the primary endpoint.  The PSA response 
rate stratified by those taking an antiandrogen and those who are not will also be 
reported. 
 
10.7 
PSA Partial Response 
 
A PSA partial response (PSA PR) is a secondary endpoint and defined as a ≥ 50% 
decrease in the PSA from the baseline assessment (after any antiandrogen washout 
period just prior to registration for patients registered with a rising PSA), confirmed by a 
second PSA measurement at least 4 weeks later.  We will also compare the number of 
subjects who obtain a confirmed PSA reduction of 90% or more compared to their 
baseline, a confirmed PSA reduction of 1.0 ng/ml or more from their baseline, and the 
number who achieve a PSA of < 4 ng/ml.   
 
11.0 
STATISTICAL CONSIDERATIONS 
 
11.1 
Accrual Rate 
 
The accrual rate is anticipated to be 30 patients per year, based on recent accrual of a 
subset of patients from SWOG-9346. 
 
 
11.2 
Analysis of Primary Endpoint 
 
The main objective of this study is to test whether this regimen has promise in terms of 
rates of undetectable PSA.  If the proportion of men with undetectable PSA is 20% or 
greater, the regimen would be of further interest, whereas further testing would not be 
pursued if the proportion of men with undetectable PSA is 5% or less.  Six or more 
subjects with undetectable PSA out of the total 38 eligible patients would indicate that 
further study of this regimen is warranted.  The design has a significance level 
(chance of falsely determining further study is warranted of a treatment with < 5% 
response rate) of 5.0% and a power (probability of correctly identifying the agent 
as warranting further study for a likely response rate of > 20%) of 90%. 


 
 
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11.3 
Analysis of Secondary Endpoints 
 
Thirty-eight eligible patients will be sufficient to estimate the PSA undetectable and 
normalization rate, the progression-free survival and the overall survival at a specified 
time point, and the probability of a particular adverse event to within +/- 16% (95% 
confidence interval). Any toxicity occurring with at least a 5% probability is likely to be 
seen at least once (83%).  
 
The 20% alternative hypothesis is based on the observation that approximately 20% of 
castrate-resistant prostate cancer (CRPC) patients treated with abiraterone acetate and 
prednisone were observed to have a > 90% PSA reduction, indicating that dramatic PSA 
responses may be expected in 20% of traditional CRPC patients treated.  (22) 
 
11.4 
Data and Safety Monitoring Committee Oversight 
 
There is no formal data and safety monitoring committee for single arm Phase II studies.  
Toxicity and accrual monitoring are done routinely by the Study Coordinator, study 
Statistician and the Disease Committee Chair.  Endpoint monitoring is done by the study 
Statistician and Study Coordinator.  Accrual reports are generated weekly and formal 
toxicity reports are generated every 6 months.  In addition, the Statistical Center, Adverse 
Event Coordinator at the Operations Office, SAE Physician Reviewer, and Study 
Coordinator monitor toxicities on an ongoing basis. 
 
 
12.0 
DISCIPLINE REVIEW 
 
There will be no formal discipline review done in conjunction with this study. 
 
 
13.0 
REGISTRATION GUIDELINES 
 
13.1 
Registration Timing 
 
Patients must be registered prior to initiation of treatment (no more than ten working days 
prior to planned start of treatment). 
 
13.2 
OPEN Registration Requirements 
 
The individual registering the patient must have completed the appropriate SWOG 
Registration Worksheet.  The completed form must be referred to during the registration 
but should not be submitted as part of the patient data. 
 
OPEN will also ask additional questions that are not present on the SWOG Registration 
Worksheet.  The individual registering the patient must be prepared to provide answers to 
the following questions: 
 
a. 
Institution CTEP ID 
 
b. 
Protocol Number 
 
c. 
Registration Step 
 
d. 
Treating Investigator 
 
e. 
Credit Investigator 
 
f. 
Patient Initials 


 
 
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g. 
Patient’s Date of Birth 
 
h. 
Patient SSN (SSN is desired, but optional.  Do not enter invalid numbers.) 
 
i. 
Country of Residence 
 
j. 
ZIP Code 
 
k. 
Gender (select one): 
• 
Female Gender 
• 
Male Gender 
 
l. 
Ethnicity (select one): 
• 
Hispanic or Latino 
• 
Not Hispanic or Latino 
• 
Unknown 
 
m. 
Method of Payment (select one): 
• 
Private Insurance 
• 
Medicare 
• 
Medicare and Private Insurance 
• 
Medicaid 
• 
Medicaid and Medicare 
• 
Military or Veterans Sponsored NOS 
• 
Military Sponsored (Including Champus & Tricare) 
• 
Veterans Sponsored 
• 
Self Pay (No Insurance) 
• 
No Means of Payment (No Insurance) 
• 
Other 
• 
Unknown 
 
n. 
Race (select all that apply): 
• 
American Indian or Alaska Native 
• 
Asian 
• 
Black or African American 
• 
Native Hawaiian or other Pacific Islander 
• 
White 
• 
Unknown 
 
13.3 
Registration procedures 
 
a. 
All site staff will use OPEN to enroll patients to this study.  OPEN is a web-based 
application and 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, or from the 
OPEN Patient Registration link on the SWOG CRA Workbench.  
 
 
b. 
Prior to accessing OPEN site staff should verify the following: 
 
• 
All eligibility criteria have been met within the protocol stated 
timeframes. Site staff should refer to Section 5.0 to verify eligibility. 
 
• 
All patients have signed an appropriate consent form and HIPAA 
authorization form (if applicable).  


 
 
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c. 
Access requirements for OPEN: 
 
• 
Site staff will need to be registered with CTEP and have a valid and 
active CTEP-IAM account. This is the same account (user ID and 
password) used for the CTSU members' web site.  
 
• 
To perform registrations on SWOG protocols you must have an 
equivalent 'Registrar' role on the SWOG roster.  Role assignments are 
handled through SWOG.  
 
Note:  The OPEN system will provide the site with a printable confirmation of 
registration and treatment information.   Please print this confirmation for your 
records.   
 
d. 
Further instructional information is provided on the OPEN tab on the CTSU 
members’ side of the 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. 
 
13.4 
Exceptions to SWOG registration policies will not be permitted. 
 
a. 
Patients must meet all eligibility requirements. 
 
b. 
Institutions must be identified as approved for registration 
 
c. 
Registrations may not be cancelled. 
 
d. 
Late registrations (after initiation of treatment) will not be accepted. 
 
 
14.0 
DATA SUBMISSION SCHEDULE 
 
14.1 
Data Submission Requirement 
 
Data must be submitted according to the protocol requirements for ALL patients 
registered, whether or not assigned treatment is administered, including patients deemed 
to be ineligible.  Patients for whom documentation is inadequate to determine eligibility 
will generally be deemed ineligible. 
 
14.2 
Master Forms 
 
Master Forms can be found on the protocol abstract page (www.swog.org) and (with the 
exception of the consent form and the Registration Worksheet) must be submitted online 
via the web; see Section 14.3a for details. 
 
14.3 
Data Submission Procedures 
 
a. 
SWOG institutions must submit data electronically via the Web by using the 
SWOG CRA Workbench.  To access the CRA Workbench, go to the SWOG Web 
site (http://swog.org) and logon to the Members Area.  After you have logged on, 
click on the CRA Workbench link to access the home page for CRA Workbench 
website.  Next, click on the Data Submission link and follow the instructions.  For 
new users, the link to a "Starter Kit" of help files may be found by clicking on the 
Starter Kit link at the Members’ logon page. 


 
 
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To submit data via the web the following must be done (in order): 
 
1. 
You are entered into the SWOG Roster and issued a SWOG Roster ID 
Number, 
2. 
You are associated as an investigator or CRA/RN at the institution where 
the patient is being treated or followed, and 
3. 
Your Web User Administrator has added you as a web user and has 
given you the appropriate system permissions to submit data for that 
institution. 
 
For assistance with points 1 and 2 call the Operations Office at 210/614-8808.  
For point 3, contact your local Web User Administrator (refer to the "Who is my 
Web User Administrator?" function on the swog.org Members logon page).  For 
other 
difficulties 
with 
the 
CRA 
Workbench, 
please 
email 
technicalquestion@crab.org.   
 
b. 
If you need to submit data that are not available for online data submission, the 
only alternative is via facsimile.  Should the need for this occur, institutions may 
submit data via facsimile to 800/892-4007 or 206/342-1680 locally.  Please do 
not use cover sheet for faxed data.  Please make sure that each page of all faxed 
data include the SWOG patient number, study ID and patient initials. 
 
14.4 
Data Submission Overview and Timepoints  
 
a. 
WITHIN 7 DAYS OF REGISTRATION: 
 
Submit copies of the following: 
 
S1014 Prestudy Form  
 
Baseline Tumor Assessment Form  
 
S1014 Prostatic Specific Antigen Reporting Form  
 
Pathology Report 
 
Radiology Reports from all scans performed to assess disease at baseline 
 
b. 
EVERY 
TWELVE 
WEEKS 
UNTIL 
PROGRESSION; 
AT 
TIME 
OF 
PROGRESSION; AND AT CONFIRMATION OF PSA RESPONSE: 
 
S1014 Prostate Specific Antigen Reporting Form 
 
c. 
WITHIN 7 DAYS OF COMPLETION OF EACH CYCLE WHILE ON PROTOCOL 
TREATMENT: 
 
S1014 Treatment Form 
 
S1014 Adverse Event Form 


 
 
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d. 
EVERY TWELVE WEEKS UNTIL PROGRESSION WHILE ON PROTOCOL 
TREATMENT (AT TIME OF DISEASE ASSESSMENT): 
 
Follow-Up Tumor Assessment Form  
 
Radiologic Assessment Reports 
 
e. 
WITHIN 14 DAYS OF DISCONTINUATION OF ALL PROTOCOL TREATMENT: 
 
Off Treatment Notice   
 
Final S1014 Treatment Form   
 
Final S1014 Adverse Event Form  
 
S1014 Prostatic Specific Antigen Reporting Form 
 
f. 
AFTER OFF ALL PROTOCOL TREATMENT, EVERY SIX MONTHS FOR 
THREE YEARS OR UNTIL DEATH: 
 
Follow Up Form 
 
g. 
WITHIN 14 DAYS OF PROGRESSION/RELAPSE: 
 
S1014 Treatment Form and S1014 Adverse Event Form(if the patient was still on 
protocol treatment); OR Follow-Up Form (if the patient was off protocol 
treatment) 
documenting 
date, 
site 
and 
method 
for 
determining 
progression/relapse; S1014  Prostate Specific Antigen Reporting Form; Off 
Treatment Notice (if the patient was still on protocol treatment), and Follow-Up 
Tumor Assessment Form. 
 
h. 
WITHIN 4 WEEKS OF KNOWLEDGE OF DEATH: 
 
Notice of Death and a final S1014 Treatment Form and S1014 Adverse Event 
Form (if the patient was still on protocol treatment) or Follow-Up Form (if the 
patient was off protocol treatment) documenting death information. 
 
 
15.0 
SPECIAL INSTRUCTIONS 
 
There are no special instructions for this study. 
 
 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS 
 
The following must be observed to comply with Food and Drug Administration regulations for the 
conduct and monitoring of clinical investigations; they also represent sound research practice: 
 
Informed Consent 
 
The principles of informed consent are described by Federal Regulatory Guidelines (Federal 
Register Vol. 46, No. 17, January 27, 1981, part 50) and the Office for Protection from Research 
Risks Reports:  Protection of Human Subjects (Code of Federal Regulations 45 CFR 46).  They 
must be followed to comply with FDA regulations for the conduct and monitoring of clinical 
investigations. 


 
 
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Institutional Review 
 
This study must be approved by an appropriate institutional review committee as defined by 
Federal Regulatory Guidelines (Ref. Federal Register Vol. 46, No. 17, January 27, 1981, part 56) 
and the Office for Protection from Research Risks Reports:  Protection of Human Subjects (Code 
of Federal Regulations 45 CFR 46). 
 
Drug Accountability 
 
An investigator is required to maintain adequate records of the disposition of investigational drugs 
according to procedures and requirements governing the use of investigational new drugs as 
described in the Code of Federal Regulations 21 CFR 312. 
 
Monitoring 
 
This study will be monitored by the Clinical Data Update System (CDUS) Version 3.0.  
Cumulative CDUS data will be submitted quarterly to CTEP by electronic means.  Reports are 
due January 31, April 30, July 31 and October 31. 
 
16.1 
Adverse Event Reporting Requirements 
 
a. 
Purpose 
 
Adverse event data collection and reporting, which are required as part of every 
clinical trial, are done to ensure the safety of patients enrolled in the studies as 
well as those who will enroll in future studies using similar agents. Adverse events 
are reported in a routine manner at scheduled times during a trial. (Directions for 
routine reporting are provided in Section 14.0.) Additionally, certain adverse 
events must be reported in an expedited manner to allow for more timely 
monitoring of patient safety and care. The following guidelines prescribe 
expedited adverse event reporting for this protocol. See also Appendix 18.1 for 
general and background information about expedited reporting. 
 
b. 
Reporting method 
 
This study requires that expedited adverse events be reported using the Cancer 
Therapy Evaluation Program Adverse Event Reporting System (CTEP-AERS).  
CTEP's guidelines for CTEP-AERS can be found at http://ctep.cancer.gov. A 
CTEP-AERS report must be submitted to the SWOG Operations Office 
electronically via the CTEP-AERS Web-based application located at: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/adverse_events.htm. 
 
c. 
When to report an event in an expedited manner 
 
Some adverse events require 24-hour notification (refer to Table 16.1) via CTEP-
AERS. When Internet connectivity is disrupted, a 24-hour notification is to be 
made to the SWOG Operations Office by telephone at 210-614-8808 or by email 
at adr@swog.org. Once Internet connectivity is restored, a 24-hour notification 
that was made by phone or using adr@swog.org must be entered electronically 
into CTEP-AERS by the original submitter at the site. 
 
When the adverse event requires expedited reporting, submit the report within 
the number of calendar days of learning of the event specified in Table 16.1.  
 
d. 
Other recipients of adverse event reports 
 
The SWOG Operations Office will forward reports and documentation to the 
appropriate regulatory agencies and drug companies as required. 
 


 
 
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Adverse events determined to be reportable to the Institutional Review Board 
responsible for oversight of the patient must be reported according to local policy 
and procedures. 
 
e. 
Expedited reporting for investigational agents 
 
Expedited reporting is required if the patient has received at least one dose of the 
investigational agent as part of the trial. Reporting requirements are provided in 
Table 16.1. The investigational agent used in this study is abiraterone acetate.  If 
there is any question about the reportability of an adverse event or if on-line 
CTEP-AERS cannot be used, please telephone or email the SAE Specialist at 
the Operations Office, 210/614-8808 or adr@swog.org, before preparing the 
report. 


 
 
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Table 16.1: 
 
Late Phase 2 and Phase 3 Studies:  Expedited Reporting Requirements for Adverse Events that 
Occur on Studies under a Non-CTEP IND within 30 Days of the Last Administration of the 
Investigational Agent/Intervention1 Abiraterone Acetate. 
 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE:  Investigators MUST immediately report to the sponsor (NCI) ANY Serious Adverse Events, whether or 
not they are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
 
 An adverse event is considered serious if it results in ANY of the following outcomes:   
1) 
Death 
2) 
A life-threatening adverse event  
3) 
An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for 
≥ 24 hours  
4) 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions  
5) 
A congenital anomaly/birth defect.  
6) 
Important Medical Events (IME) that may not result in death, be life threatening, or require 
hospitalization may be considered serious when, based upon medical judgment, they may jeopardize 
the patient or subject and may require medical or surgical intervention to prevent one of the outcomes 
listed in this definition. (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the NCI via 
CTEP-AERS within the timeframes detailed in the table below. 
Hospitalization 
Grade 1 
Timeframes 
Grade 2 
Timeframes 
Grade 3 
Timeframes 
Grade 4 & 5 
Timeframes 
Resulting in 
Hospitalization ≥ 24 hrs 
10 Calendar Days 
24-Hour 5 
Calendar 
Days 
Not resulting in 
Hospitalization  
≥ 24 hrs 
Not required 
10 Calendar Days 
NOTE:  Protocol specific exceptions to expedited reporting of serious adverse events are found in the 
Specific Protocol Exceptions to Expedited Reporting (SPEER) portion of the CAEPR or [Section 
16.1f.]  
Expedited AE reporting timelines are defined as: 
o “24-Hour; 5 Calendar Days” - The AE must initially be reported via CTEP-AERS within 24 hours of 
learning of the AE, followed by a complete expedited report within 5 calendar days of the initial 
24-hour report. 
 
o “10 Calendar Days” - A complete expedited report on the AE must be submitted within 10 calendar 
days of learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows:  
 
Expedited 24-hour notification followed by complete report within 5 calendar days for: 
• All Grade 4, and Grade 5 AEs 
Expedited 10 calendar day reports for: 
• Grade 2 adverse events resulting in hospitalization or prolongation of hospitalization  
• Grade 3 adverse events 
May 5, 2011 
 


 
 
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f. 
Additional Instructions or Exceptions to CTEP-AERS Expedited Reporting 
Requirements for Late Phase 2 and Phase 3 Studies Utilizing an Agent 
under a Non-CTEP IND: 
 
1. 
Group-specific instructions. 
 
Supporting Documentation Submission - Within 5 calendar days 
submit the following to the SWOG Operations Office by fax to 210-
614-0006 or mail to the address below: 
• 
Printed copy of the first page of the CTEP-AERS report 
• 
Copies of clinical source documentation of the event 
• 
If applicable, and they have not yet been submitted to the 
SWOG Data Operations Center, copies of Off Treatment 
Notice and/or Notice of Death. 
 
2. 
The adverse event listed below does not require expedited reporting via 
CTEP-AERS: 
• 
Grade 4 myelosuppression 
 
g. 
Reporting Secondary Malignancy, including AML/ALL/MDS 
 
1. 
A secondary malignancy is a cancer caused by treatment for a previous 
malignancy (e.g., treatment with investigational agent/intervention, 
radiation or chemotherapy).  A secondary malignancy is not considered a 
metastasis of the initial neoplasm. 
 
 
SWOG requires all secondary malignancies that occur following 
treatment with an agent under a non-NCI IND to be reported via 
CTEP-AERS.  Three options are available to describe the event. 
 
• 
Leukemia secondary to oncology chemotherapy (e.g., 
Acute Myelocytic Leukemia [AML]) 
 
• 
Myelodysplastic syndrome (MDS) 
 
• 
Treatment-related secondary malignancy 
 
 
Any malignancy possibly related to cancer treatment (including 
AML/MDS) should also be reported via the routine reporting 
mechanisms outlined in each protocol. 
 
Second Malignancy: A second malignancy is one unrelated to the 
treatment of a prior malignancy (and is NOT a metastasis from the 
initial malignancy).  Second malignancies require ONLY routine 
reporting via CDUS unless otherwise specified. 
 
For more information see: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/d
ocs/aeguidelines.pdf  
 
2. 
Supporting documentation should be submitted to CTEP in accordance 
with instructions provided by the CTEP-AERS system.  A copy of the 
report and the following supporting documentation must also be 
submitted to the SWOG Operations Office within 30 days: 
 


 
 
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• 
a copy of the pathology report confirming the AML/ALL 
/MDS diagnosis 
• 
(if available) a copy of the cytogenetics report 
 
SWOG 
ATTN: SAE Program 
4201 Medical Drive, Suite 250 
San Antonio, Texas 78229 
 
NOTE: If a patient has been enrolled in more than one NCI-sponsored study, the 
report must be submitted for the most recent trial. 
 
17.0 
BIBLIOGRAPHY 
 
1  
Huggins C, Hodges CV.  Studies on prostatic cancer: I. The effect of castration, of estrogen and 
of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. 1941. J 
Urol 168:9-12, 2002. 
 
2  
Hussain M, Tangen CM, Higano C, et al.  Absolute prostate-specific antigen value after androgen 
deprivation is a strong independent predictor of survival in new metastatic prostate cancer: data 
from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol 24:3984-90, 2006. 
 
3  
Hellerstedt BA, Pienta KJ.  The current state of hormonal therapy for prostate cancer. CA Cancer 
J Clin 52:154-79, 2002. 
 
4  
Stigliano A, Gandini O, Cerquetti L, et al.  Increased metastatic lymph node 64 and CYP17 
expression are associated with high stage prostate cancer. J Endocrinol 194:55-61, 2007. 
 
5  
Stanbrough M, Bubley GJ, Ross K, et al.  Increased expression of genes converting adrenal 
androgens to testosterone in androgen-independent prostate cancer. Cancer Res 66:2815-25, 
2006. 
 
6  
Titus MA, Schell MJ, Lih FB, et al.  Testosterone and dihydrotestosterone tissue levels in 
recurrent prostate cancer. Clin Cancer Res 11:4653-7, 2005. 
 
7  
Stanbrough M, Bubley GJ, Ross K, et al.  Increased expression of genes converting adrenal 
androgens to testosterone in androgen-independent prostate cancer. Cancer Res 66:2815-25, 
2006. 
 
8  
Edwards J, Krishna NS, Grigor KM, et al.  Androgen receptor gene amplification and protein 
expression in hormone refractory prostate cancer. Br J Cancer 89:552-6, 2003. 
 
9  
Chen CD, Welsbie DS, Tran C, et al.  Molecular determinants of resistance to antiandrogen 
therapy. Nat Med 10:33-9, 2004. 
 
10  
Haidar S, Ehmer PB, Barassin S, et al.  Effects of novel 17alpha-hydroxylase/C17, 20-lyase 
(P450 17, CYP 17) inhibitors on androgen biosynthesis in vitro and in vivo. J Steroid Biochem Mol 
Biol 84:555-62, 2003. 
 
11  
Small EJ, Halabi S, Dawson NA, et al.  Antiandrogen withdrawal alone or in combination with 
ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). 
J Clin Oncol 22:1025-33, 2004. 
 
12  
Harris KA, Weinberg V, Bok RA, et al.  Low dose ketoconazole with replacement doses of 
hydrocortisone in patients with progressive androgen independent prostate cancer. J Urol 
168:542-5, 2002. 
 


 
 
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13  
Small EJ, Baron AD, Fippin L, et al.  Ketoconazole retains activity in advanced prostate cancer 
patients with progression despite flutamide withdrawal. J Urol 157:1204-7, 1997. 
 
14  
Small EJ, Baron A, Bok R. Simultaneous antiandrogen withdrawal and treatment with 
ketoconazole and hydrocortisone in patients with advanced prostate carcinoma. Cancer 80:1755-
9, 1997. 
 
15  
Ryan CJ, Halabi S, Ou SS, et al. Adrenal androgen levels as predictors of outcome in prostate 
cancer patients treated with ketoconazole plus antiandrogen withdrawal: results from a cancer 
and leukemia group B study. Clin Cancer Res 13:2030-7, 2007. 
 
16  
Attard G, Reid AH, Yap TA, et al.  Phase I clinical trial of a selective inhibitor of CYP17, 
abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains 
hormone driven. J Clin Oncol, 2008. 
 
17  
Attard G, Reid AH, Yap TA, et al.  Phase I clinical trial of a selective inhibitor of CYP17, 
abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains 
hormone driven. J Clin Oncol, 2008. 
 
 
18  
O'Donnell A, Judson I, Dowsett M, et al.  Hormonal impact of the 17alpha-hydroxylase/C(17,20)-
lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer 
90:2317-25, 2004. 
 
19  
Ryan C, Smith MR, Rosenberg J, et al.  Impact of prior ketoconazole therapy on response 
proportion to abiraterone acetate, a 17 alpha hydroxylase c17,20-lyase inhibitor in castration 
resistant prostate cancer. (abstract 157). J Clin Oncol 26 (May 20 suppl; abstract 5018), 2008. 
 
20  
Danila DC, Rathkopf D, Morris M, et al.  Abiraterone acetate and prednisone in patients with 
progressive metastatic castration resistant prostate cancer (CRPC) after failure of docetaxel-
based chemotherapy. J Clin Oncol 26 (May 20 suppl: abstract 5019), 2008. 
 
21  
Riggs SB, Lee G, La Rochelle J, et al.  Development of an ultrasensitive testosterone (UST) 
assay to redefine castration resistant prostate cancer (CRPC): An important tool for future 
research and clinical decisions. Proceedings of the 2008 Genitourinary Cancer Symposium: #68, 
2008. 
 
22  
Attard G, Reid AH, Yap TA, et al.  Phase I clinical trial of a selective inhibitor of CYP17, 
abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains 
hormone driven. J Clin Oncol, 2008. 
 
23  
WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M. Prostate Cancer Clinical 
Trials Working Group. Design and end points of clinical trials for patients with progressive 
prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer 
Clinical Trials Working Group. J Clin Oncol 26(7):1148-59, 2008. 
 


 
 
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18.0 
APPENDIX 
 
18.1 
Determination of Expedited Adverse Event Reporting Requirements 
 
18.2 
Intake Calendar  
 
18.3 
Potential Drug Interaction with Abiraterone Acetate 
 
18.4 
Child-Pugh Classification (CPC) of Liver Dysfunction 


 
 
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18.1 
Determination of Expedited Adverse Event Reporting Requirements 
 
Adverse event data collection and reporting, which are required as part of every clinical 
trial, are done to ensure the safety of patients enrolled in the studies as well as those who 
will enroll in future studies using similar agents. Adverse events are reported in a routine 
manner at scheduled times during a trial. (Directions for routine reporting are provided in 
Section 14.0.) Additionally, certain adverse events must be reported in an expedited 
manner to allow for more timely monitoring of patient safety and care. Expedited adverse 
event reporting principles and general guidelines follow; specific guidelines for expedited 
adverse event reporting on this protocol are found in Section 16.1. 
 
All serious adverse events determined to be reportable to the Institutional Review Board 
responsible for the oversight of the patient must be reported according to local policy and 
procedures.  Documentation of this reporting should be maintained for possible 
inspection during quality assurance audits. 
 
• 
Steps to determine if an adverse event is to be reported in an expedited 
manner (This includes all events that occur while on treatment or within 30 days of 
the last dose of protocol treatment.) 
 
Step 1: Determine whether the patient has received an investigational agent, commercial 
agent, or a combination of investigational and commercial agents. 
 
An investigational agent is a protocol drug administered under an Investigational New 
Drug Submission (IND). In some instances, the investigational agent may be available 
commercially, but is actually being tested for indications not included in the approved 
package label.  
 
Commercial agents are those agents not provided under an IND but obtained instead 
from a commercial source. The NCI, rather than a commercial distributor, may on some 
occasions distribute commercial agents for a trial. 
• 
When a study includes both investigational and commercial agents, the 
following rules apply.   
• 
Concurrent administration: When an investigational agent(s) is used in 
combination with a commercial agent(s), the combination is considered to be 
investigational and expedited reporting of adverse events would follow the 
guidelines for investigational agents. 
• 
Sequential administration:   When a study includes an investigational agent(s) and 
a commercial agent(s) on the same study arm with sequential administration all 
expedited reporting of adverse events should follow the guidelines for the type of 
agent being given.  For example, if the patient begins the study on the investigational 
agent(s), then all expedited reporting of adverse events should follow guidelines for 
the investigational agent(s).  Once the patient begins receiving the commercial 
agent(s) then all expedited reporting of adverse events should follow the guidelines 
for commercial agent(s).   
 
Step 2: Identify the type of event using the NCI Common Terminology Criteria for 
Adverse Events (CTCAE). The CTCAE provides descriptive terminology and a grading 
scale for each adverse event listed. A copy of the CTCAE can be downloaded from the 
CTEP home page (http://ctep.cancer.gov). Additionally, if assistance is needed, the NCI 
has an Index to the CTCAE that provides help for classifying and locating terms.  
 
Step 3:  Grade the event using the NCI CTCAE version specified in the protocol for 
reporting serious adverse events 
 


 
 
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Step 4: Determine if the adverse event is Expected or an Exception to Expedited 
Reporting.  Expected events are those that have been previously identified as resulting 
from administration of the agent and are listed in one of the following:   
 
• 
The current NCI SPEER (Specific Protocol Exceptions to Expedited Reporting) 
for treatments using agents provided under an NCI-held IND, or an equivalent 
listing for treatments using agents provided under a Non-CTEP-held IND; located 
in Section 3.0 of the protocol. 
• 
For treatments using commercial agents, the current CAEPR (Comprehensive 
Adverse Event and Potential Risks), ASAEL (Agent Specific Adverse Event List), 
or other list of expected toxicities located in Section 3.0 of the protocol, or the 
drug package insert.   
• 
Exception to Expedited reporting located in Section 16.1f of the protocol. 
 
An adverse event is considered unexpected, for expedited reporting purposes only, 
when either the type of event or the severity of the event is not listed in one of the areas 
outlined above. 
 
Step 5:  Determine whether the adverse event involved hospitalization or a prolongation of 
hospitalization (≥ 24 hours). 
 
Step 6:  Additionally, for commercial drugs, determine whether the adverse event is related to the 
protocol therapy. Attribution categories are as follows: Unrelated, Unlikely, Possible, 
Probable, and Definite.  Consult the appropriate table for expedited reporting criteria for 
commercial agent(s). 
 
NOTE:  Any event that occurs more than 30 days after the last dose of study agent and is 
attributed (possible, probable, or definite) to the study agent(s) must be reported 
according to the instructions above and as outlined in the appropriate table in Section 
16.1. 
 


 
 
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18.2 
Intake Calendar  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sunday 
Monday 
Tuesday 
Wednesday 
Thursday 
Friday 
Saturday 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Patient Signature: 
 
Instructions for the participant: 
 
This is a monthly calendar on which you are to record the number of tablets/pills/capsules you 
take each day.  Be sure you have enough calendars to last until your next appointment.  If you 
develop any side effects from the tablets/pills/capsules, mark this on the calendar on the day 
you note the effect.  Bring your calendars with you each time you have an appointment. 
 
If you have questions contact: ____________________ Telephone: _____________________ 
 
Your next appointment is: _______________________ 
Special instructions: 
 
Month: 
 
Year: 
 


 
 
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18.3 
Potential Drug Interaction with Abiraterone Acetate 
 
While abiraterone acetate exhibited inhibition of P450 CYPs 2C19, 2D6, and 1A2 in the in 
vitro enzyme interaction studies, these inhibitory effects were an order of magnitude 
weaker than those for classic inhibitors of 1A2 and 2D6, and 5 fold weaker than for 
classic inhibitors of 2C19. 
 
There have been no reports of clinically significant drug-drug interactions involving 
abiraterone.  Table 10 identifies medications that could potentially be affected in subjects 
receiving abiraterone acetate.   
 
Drug Name 
P450 Mechanism 
Possible Effect 
Clopidogrel 
2C19 needed for prodrug  
activation 
Decreased efficacy 
Ticlopidine 
2C19 needed for prodrug  
activation 
Decreased efficacy 
Metoprolol 
Metabolized by 2D6 
Increased drug levels 
Propranolol 
Metabolized by 2C19 
Increased drug levels 
Flecainide 
Metabolized by 2D6 
Increased drug levels 
Propafenone 
Metabolized by 2D6 
Increased drug levels 
Haloperidol 
Metabolized by 2D6 
Increased drug levels 
Fluoxetine 
Metabolized by 2C19 
Increased drug levels 
Paroxetine 
Metabolized by 2C19 
Increased drug levels 
Sertraline 
Metabolized by 2D6 
Increased drug levels 
Amoxapine 
Metabolized by 2C19 
Increased drug levels 
Clomipramine 
Metabolized by 2D6 
Increased drug levels 
Desipramine 
Metabolized by 2D6 
Increased drug levels 
Doxepin 
Metabolized by 2D6 
Increased drug levels 
Imipramine 
Metabolized by 2D6 
Increased drug levels 
Nortriptyline 
Metabolized by 2D6 
Increased drug levels 
Protriptyline 
Metabolized by 2D6  
Increased drug levels 
Oxycodone 
Metabolized by 2D6 
Increased drug levels 
Codeine 
Prodrug activated by 2D6 to  
form Morphine 
Decreased efficacy 
Tamoxifen 
Prodrug activated by 2D6 
Decreased efficacy 
Theophylline 
Metabolized by 1A2 
Increased drug levels 
Cimetidine 
Metabolized by 2C19 
Increased drug levels 


 
 
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18.4 
Child-Pugh Classification (CPC) of Liver Dysfunction 
 
CPC score is calculated from the sum of the points for each CPC criteria: 
CPC Classification 
Level of dysfunction 
Score 
A 
mild 
5-6 
B 
moderate 
7-9 
C 
severe 
≥ 10 
 
 
Points 
CPC Criteria 
1 
2 
3 
Encephalopathy grade 
(see table below) 
0 
1 or 2 
3 or 4 
Ascites 
Absent 
Asymptomatic 
Requiring intervention 
Serum bilirubin, mg/dL 
< 2 
2 to 3 
> 3 
Serum albumin, g/dL 
> 3.5 
2.8 to 3.5 
< 2.8 
Prothrombin time, sec 
prolonged 
< 4 
4 to 6 
> 6 
 
Encephalopathy 
Grade 
Definition 
(EEG required for Gr. 2,3,4) 
0 
Normal consciousness, personality, neurological exam 
1 
Restless, 
sleep 
disturbed, 
irritable/agitated, 
tremor, 
impaired handwriting 
2 
Lethargic, time-disoriented, inappropriate, asterixis, ataxia, 
slow triphasic  
waves on EEG 
3 
Somnolent, 
stuporous, 
place-disoriented, 
hyperactive 
reflexes, rigidity,  
slower waves on EEG 
4 
Unrousable coma, no personality/behavior, decerebrate, 
slow 2-3 cps delta  
activity on EEG 
CPC should be calculated at baseline and prior to each treatment cycle 
 


 
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Informed Consent Model for S1014 
*NOTES FOR LOCAL INSTITUTION INFORMED CONSENT AUTHORS:  
 
This model informed consent form has been reviewed by the DCTD/NCI and is the official 
consent document for this study. Local IRB changes to this document are allowed.  (Institutions 
should attempt to use sections of this document that are in bold type in their entirety.)  Editorial 
changes to these sections may be made as long as they do not change information or intent.  If 
the institutional IRB insists on making deletions or more substantive modifications to the risks or 
alternatives sections, they may be justified in writing by the investigator and approved by the 
IRB.  Under these circumstances, the revised language, justification and a copy of the IRB 
minutes must be forwarded to the SWOG Operations Office for approval before a patient may be 
registered to this study.   
 
Readability Statistics:   
 
Flesch Reading Ease  
60 (targeted above 55) 
Flesch-Kincaid Grade Level 8.5 (targeted below 8.5) 
 
• Instructions and examples for informed consent authors are in [italics].  
• A blank line,  __________, indicates that the local investigator should provide the 
appropriate information before the document is reviewed with the prospective research 
participant.  
• The term "study doctor" has been used throughout the model because the local 
investigator for a cancer treatment trial is a physician.   If this model is used for a trial 
in which the local investigator is not a physician, another appropriate term should be 
used instead of "study doctor".  
• The dates of protocol updates in the header and in the text of the consent is for 
reference to this model only and should not be included in the informed consent form 
given to the prospective research participant.  
• The local informed consent must state which parties may inspect the research records. 
This includes the NCI, the drug manufacturer for investigational studies, any 
companies or grantors that are providing study support (these will be listed in the 
protocol's model informed consent form) and SWOG.  
 
SWOG must be listed as one of the parties that may inspect the research records in all 
protocol consent forms for which patient registration is being credited to SWOG.  This 
includes consent forms for studies where all patients are registered directly through 
SWOG, all intergroup studies for which the registration is being credited to the 
(whether the registration is through the SWOG Data Operations Office or directly 
through the other group), as well as consent forms for studies where patients are 
registered via CTSU and the registration is credited to SWOG. 
• When changes to the protocol require revision of the informed consent document, the 
IRB should have a system that identifies the revised consent document, in order to 
preclude continued use of the older version and to identify file copies.  An appropriate 
method to identify the current version of the consent is for the IRB to stamp the final 


 
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copy of the consent document with the approval date.  The stamped consent document 
is then photocopied for use.  Other systems of identifying the current version of the 
consent such as adding a version or approval date are allowed as long as it is possible 
to determine during an audit that the patient signed the most current version of the 
consent form.  
 
*NOTES FOR LOCAL INVESTIGATORS:  
• The goal of the informed consent process is to provide people with sufficient 
information for making informed choices.   The informed consent form provides a 
summary of the clinical study and the individual's rights as a research participant.  It 
serves as a starting point for the necessary exchange of information between the 
investigator and potential research participant.  This model for the informed consent 
form is only one part of the larger process of informed consent. For more information 
about informed consent, review the "Recommendations for the Development of 
Informed Consent Documents for Cancer Clinical Trials" prepared by the 
Comprehensive Working Group on Informed Consent in Cancer Clinical Trials for the 
National Cancer Institute.  The Web site address for this document is 
http://cancer.gov/clinicaltrials/understanding/simplification-of-informed-consent-docs/ 
• A blank line,  __________, indicates that the local investigator should provide the 
appropriate information before the document is reviewed with the prospective research 
participant.  
• Suggestion for Local Investigators:  An NCI pamphlet explaining clinical trials is 
available for your patients.  The pamphlet is titled: "If You Have Cancer…What You 
Should Know about Clinical Trials".  This pamphlet may be ordered on the NCI Web 
site at https://cissecure.nci.nih.gov/ncipubs or call 1-800-4- CANCER (1-800-422-
6237) to request a free copy.  
• Optional feature for Local Investigators: Reference and attach drug sheets, 
pharmaceutical information for the public, or other material on risks.  Check with your 
local IRB regarding review of additional materials. 
 
*These notes for authors and investigators are instructional and should not be included in the 
informed consent form given to the prospective research participant.  
 


 
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S1014, "Abiraterone Acetate Treatment for Prostate Cancer Patients 
with a PSA of More Than Four Following Initial Androgen Deprivation 
Therapy, Phase II" 
 
This is a clinical trial, a type of research study.  Your study doctor will explain the clinical trial 
to you.  Clinical trials include only people who choose to take part. Please take your time to 
make your decision about taking part.  You may discuss your decision with your friends and 
family.  You can also discuss it with your health care team.  If you have any questions, you can 
ask your study doctor for more explanation.  
 
You are being asked to take part in this study because you have prostate cancer that is only 
partially responding to hormone therapy.  Abiraterone acetate is a hormonal tablet that has been 
approved by the Food and Drug Administration (FDA) for more advanced prostate cancer 
patients who have received chemotherapy.  It is considered investigational for your type of 
prostate cancer.  We will be looking to see if abiraterone acetate improves the effectiveness of 
standard hormonal shots or injections.  The prostate specific antigen (PSA) is a blood test used in 
prostate cancer screening and also to follow prostate cancer.  In this study, we will follow your 
PSA level to help determine if abiraterone acetate is beneficial.  The main goal of this study is to 
see if abiraterone acetate with prednisone reduces PSA. 
 
Who is doing this study? 
 
SWOG is sponsoring this trial.  SWOG is an adult cancer clinical trials organization. SWOG is 
funded through the National Cancer Institute, and its network consists of about four thousand 
physicians at almost three hundred institutions throughout the United States.  Your study doctor 
has met all requirements to be a member of SWOG and to perform National Cancer Institute-
funded research through this Group. 
 
Why is this study being done? 
The purpose of this study is to find out what effects, good and/or bad, abiraterone acetate 
has on you and your prostate cancer.  The effect of the prostate cancer will be measured by 
a blood test (prostatic specific antigen or PSA). 
 
How many people will take part in the study? 
About 38 people will take part in this study.   
 
What will happen if I take part in this research study?   
 
Before you begin the study …  
 


 
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You will need to have the following exams, tests or procedures to find out if you can be in the 
study.  These exams, tests or procedures are part of regular cancer care and may be done even if 
you do not join the study.  If you have had some of them recently, they may not need to be 
repeated.  This will be up to your study doctor. 
 
• History and physical exam including measuring your blood pressure 
• CT scan of your abdomen and pelvis 
• Bone scan 
• Blood prostate specific antigen (PSA) test 
• Other blood tests including those to assess your blood counts, kidney and liver 
function, and testosterone level. 
• CT or MRI scan of the brain if your doctor feels it's necessary 
 
During the study …  
If the exams, tests and procedures show that you can be in the study, and you choose to take part, 
then you will need the following tests and procedures.  They are part of regular cancer care.  
 
Every 2 weeks for the first 3 months: 
• Blood tests to monitor your liver 
 
Every 4 weeks: 
• History and physical exam including measuring your blood pressure 
• Blood prostate specific antigen (PSA) test 
• Other blood tests including those to assess your blood counts, kidney and liver 
function. 
 
Every 12 weeks: 
• CT scan of your abdomen and pelvis 
• Bone scan 
 
Treatment will consist of taking 4 abiraterone acetate tablets a day.  Abiraterone acetate must be 
taken on an empty stomach.  You should not eat for at least two hours before the dose of 
abiraterone acetate and for at least one hour after abiraterone acetate is taken.  You will also take 
one prednisone tablet twice a day.  Prednisone is a type of drug called a corticosteroid.  It is a 
standard treatment for prostate cancer and may improve your symptoms.  Prednisone also 
reduces some of the potential side effects associated with abiraterone acetate.  Abiraterone 
acetate and prednisone can be taken together.  Every 28 days is called a cycle.  You will continue 
taking abiraterone acetate and prednisone as long as your disease does not get worse and side 
effects do not become too severe.  To help keep track of the number of tablets you take and any 
side effects, you will need to keep a pill diary.  The pill diary is called an Intake Calendar and 
you will need to bring it with you for your follow-up visits.  Although it reflects a month's time, 
you should complete it daily.  You need only complete one Intake Calendar for both drugs.   


 
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When I am finished taking abiraterone acetate… 
After you are done taking the study drug, there will be an end of study visit.  A history and 
physical exam with routine blood tests will be done at that time.  The study personnel will 
continue to follow your progress approximately every 3 months for the first year after you join 
the study and then every 6 months thereafter for up to 3 years.  
How long will I be in the study? 
 
You will be asked to take abiraterone acetate for as long as you tolerate the treatment and it is 
working.  After you are finished taking abiraterone acetate, the study doctor will ask you to visit 
the office for follow-up exams for at least up to 3 years from the time you started the study. 
 
Can I stop being in the study? 
 
Yes.  You can decide to stop at any time.  Tell the study doctor if you are thinking about 
stopping or decide to stop.  He or she will tell you how to stop safely.  
 
It is important to tell the study doctor if you are thinking about stopping so any risks from the 
abiraterone acetate can be evaluated by your doctor.  Another reason to tell your doctor that you 
are thinking about stopping is to discuss what follow-up care and testing could be most helpful 
for you. 
 
The study doctor may stop you from taking part in this study at any time if he/she believes it is in 
your best interest, if you do not follow the study rules, or if the study is stopped. 
 
What side effects or risks can I expect from being in the study?  
 
You may have side effects while on the study.  Everyone taking part in the study will be 
watched carefully for any side effects.  However, doctors don’t know all the side effects that 
may happen.  Side effects may be mild or very serious. Your health care team may give you 
medicines to help lessen side effects. Many side effects go away soon after you stop taking 
the abiraterone acetate. In some cases, side effects can be serious, long lasting, or may 
never go away. There also is a risk of death.  
 
There is a small chance of severe allergic reaction to the study drug which may be life-
threatening. Abiraterone acetate may cause harm to the liver. Fewer than 10% of patients 
who took the study drug have had abnormal blood levels of liver enzymes. Rarely, liver 
failure may occur, which can lead to death. Pausing or ending the treatment helped to 
make liver function normal again in most of these cases. Your liver function will be 
checked closely with blood tests every two weeks for the first 3 months of the study and 
then monthly after. If your liver tests are abnormal, the dose of your study drug will be 
reduced or stopped. Abiraterone acetate should be used carefully in patients with a history 
of heart disease. Before treatment with the study drug, high blood pressure must be 


 
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controlled and low potassium must be corrected.  Potassium is needed for proper function 
of your heart, and other important body systems.  
 
You should talk to your study doctor about any side effects that you have while taking part 
in the study.   
 
Risks and side effects related to the abiraterone acetate include those which are: 
 
Frequent (≥ 20%) [May occur in 20 or more patients in 100]  
• hypokalemia (low blood potassium, a mineral that helps regulate heart rate/function, fluid 
balance in the body and is needed for adequate body function) 
• hypertension (high blood pressure) 
 
Very Common (≥ 10% to <20%) [May occur between 10 and 19 patients in 100] 
• edema peripheral (swelling of the legs as a result of the body keeping too much fluid) 
 
Common (≥ 5% to <10%) [May occur between 5 to 9 patients in 100] 
• dyspepsia (uncomfortable feeling in upper belly, indigestion) 
• hematuria (presence of blood in the urine)  
• Alanine aminotransferase increased and/or aspartate aminotransferase increased 
(enzymes in the blood that measure the function of the liver) 
• urinary tract infection 
• fractures (a break in the bone) 
 
Less Common (≥1% to < 5% [May occur in fewer than 5 patients in 100] 
• hypertriglyceridemia (high levels of fats (triglycerides) in the blood)  
• angina pectoris (chest pain from the heart) 
• atrial fibrillation (a fast and irregular heartbeat) 
• tachycardia (rapid heartbeats) 
 
Uncommon (< 1%) [May occur in less than 9 patients in 1000]  
• adrenal insufficiency (decreased function of adrenal glands that normally help maintain 
blood pressure, balance minerals and fluid in your body)  
• cardiac failure (heart failure, the heart is unable to supply enough blood flow to meet the 
body's needs.) 
• arrhythmia (changes in the rhythm of the heart) 
• abnormal ECG with QT prolongation (an abnormal finding on the ECG) 
•  bone density decreased (loss of strength of bones)  
• myopathy (muscle weakness and/or muscle pain) 
 
Unknown (frequency isn’t determined since data was derived from post-marketing experience 
and there was no report from clinical studies) 
• allergic alveolitis (swelling and irritation of the lung) 


 
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• failure of the liver to function (called acute liver failure). 
• Rhabdomyolysis (breakdown of muscle tissue)  
• Torsades de Pointes (rapid or irregular heart rate associated with feeling faint or 
lightheaded) 
 
Possible adverse effects associated with the use of prednisone are: fluid and electrolyte 
disturbances, congestive heart failure in susceptible persons, hypertension, euphoria, 
personality changes, insomnia, mood swings, depression, exacerbation of infection (e.g., 
tuberculosis), exacerbation or symptoms of diabetes, psychosis, muscle weakness, 
osteoporosis, vertebral compression fractures, pancreatitis, esophagitis, peptic ulcer 
disease, dermatologic disturbances, convulsions, vertigo and headache, endocrine 
abnormalities, ophthalmic changes, and metabolic changes. Some patients have 
experienced itching and other allergic, anaphylactic or other hypersensitivity reactions. 
Withdrawal from prolonged therapy may result in symptoms of adrenal insufficiency 
including fever, myalgia and arthralgia. 
 
Reproductive risks:  You should not father a baby while on this study and for at least 1 
week after you stop taking abiraterone acetate. Based on animal studies, abiraterone 
acetate may harm the unborn child.  Male patients who are receiving abiraterone acetate 
and who have a partner of childbearing potential are advised to use a method of birth 
control with adequate barrier protection (e.g. condoms) as determined to be acceptable by 
your study doctor. Check with your study doctor about what kind of birth control methods 
to use and how long to use them.  Some methods might not be approved for use in this 
study.  
 
Handling abiraterone acetate tablets: 
 
This medicine may cause harm to the unborn child if given to women who are pregnant.  It 
should not be taken by women who are breast feeding.  Women who are pregnant or who 
may be pregnant should wear gloves if they need to touch abiraterone acetate tablets.  You 
should notify any caregivers of this information to ensure that appropriate precautions are 
taken.   
 
For more information about risks and side effects, ask your study doctor. 
 
Are there benefits to taking part in the study? 
 
Taking part in this study may or may not make your health better.  While doctors hope 
abiraterone acetate will be more useful against cancer compared to the usual treatment, there is 
no proof of this yet. We do know that the information from this study will help doctors learn 
more about abiraterone acetate as a treatment for prostate cancer.  This information could help 
future cancer patients. 


 
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What other choices do I have if I do not take part in this study? 
 
Your other choices may include: 
• Getting treatment or care for your cancer without being in a study 
• Taking part in another study 
• Getting no treatment 
 
Talk to your doctor about your choices before you decide if you will take part in this study. 
Will my medical information be kept private?  
 
We will do our best to make sure that the personal information in your medical record will be 
kept private.  However, we cannot guarantee total privacy.  Your personal information may be 
given out if required by law.  If information from this study is published or presented at scientific 
meetings, your name and other personal information will not be used.  
 
Organizations that may look at and/or copy your medical records for research, quality assurance, 
and data analysis include: 
• The National Cancer Institute (NCI) and other government agencies, like the Food and 
Drug Administration (FDA), involved in keeping research safe for people 
• SWOG 
• A qualified representative of the manufacturer of abiraterone acetate, Janssen Scientific 
Affairs, LLC. 
 
A description of this study will be available on http://www.clinicaltrials.gov, as required by U.S. 
Law.  This website will not include information that can identify you.  At most, the web site will 
include a summary of the results of the study.  You can search this website at any time. 
 
[Note to Local Investigators: The NCI has recommended that HIPAA regulations be addressed 
by the local institution.  The regulations may or may not be included in the informed consent 
form depending on local institutional policy.] 
 
What are the costs of taking part in this study? 
 
You and/or your health plan/ insurance company will need to pay for some or all of the costs of 
treating your cancer in this study.  Some health plans will not pay these costs for people taking 
part in studies.  Check with your health plan or insurance company to find out what they will pay 
for.  Taking part in this study may or may not cost your insurance company more than the cost of 
getting regular cancer treatment.  
 
Janssen Scientific Affairs, LLC will supply the abiraterone acetate at no charge while you take 
part in this study.  Janssen Scientific Affairs, LLC will also provide funding for distribution of 
drug to the participating treatment sites.  Janssen Scientific Affairs, LLC does not cover the cost 


 
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of getting the abiraterone acetate ready and giving it to you, so you or your insurance company 
may have to pay for this. 
 
Even though it probably won’t happen, it is possible that the manufacturer may not continue to 
provide abiraterone acetate for some reason.  If this would occur, other possible options are:   
• Abiraterone acetate is not currently approved by the FDA for sale in the United States for 
your type of prostate cancer.  If the FDA approves the sale of this drug for your type of 
prostate cancer and if the manufacturer chooses to discontinue supplying the drug free of 
charge for this study, you might be able to get the abiraterone acetate directly from the 
manufacturer or your pharmacy but you or your insurance company may have to pay for 
it. 
• If there is no abiraterone acetate available at all, no one will be able to get more and the 
study would close. 
 
If a problem with getting abiraterone acetate occurs, your study doctor will talk to you about 
these options. 
 
Prednisone, goserelin acetate, leuprolide acetate, and Degarelix are commercially available and 
will not be provided free of charge. 
 
You will not be paid for taking part in this study. 
 
For more information on clinical trials and insurance coverage, you can visit the National Cancer 
Institute’s Web site at http://cancer.gov/clinicaltrials/understanding/insurance-coverage.  You 
can print a copy of the "Clinical Trials and Insurance Coverage" information from this Web site. 
 
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and ask them 
to send you a free copy. 
 
What happens if I am injured because I took part in this study? 
 
It is important that you tell your study doctor, __________________ [investigator’s name(s)], if 
you feel that you have been injured because of taking part in this study.  You can tell the doctor 
in person or call him/her at __________________ [telephone number]. 
 
You will get medical treatment if you are injured as a result of taking part in this study.  You 
and/or your health plan will be charged for this treatment.   The study will not pay for medical 
treatment.   
What are my rights if I take part in this study? 
 
Taking part in this study is your choice.  You may choose either to take part or not to take part in 
the study.  If you decide to take part in this study, you may leave the study at any time.   No 
matter what decision you make, there will be no penalty to you and you will not lose any of your 


 
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regular benefits.  Leaving the study will not affect your medical care.  You can still get your 
medical care from our institution.    
 
We will tell you about new information or changes in the study that may affect your health or 
your willingness to continue in the study. 
 
In the case of injury resulting from this study, you do not lose any of your legal rights to seek 
payment by signing this form.   
 
Who can answer my questions about the study? 
 
You can talk to your study doctor about any questions or concerns you have about this study.  
Contact your study doctor __________________ [name(s)] at __________________ [telephone 
number]. 
 
For questions about your rights while taking part in this study, call the 
________________________ [name of center] Institutional Review Board (a group of people 
who review the research to protect your rights) at __________________ (telephone number).  
[Note to Local Investigator: Contact information for patient representatives or other individuals 
in a local institution who are not on the IRB or research team but take calls regarding clinical 
trial questions can be listed here.]   
 
Please note:  This section of the informed consent form is about additional research 
studies that are being done with people who are taking part in the main study.   
You may take part in these additional studies if you want to.  You can still be a part 
of the main study even if you say 'no' to taking part in any of these additional 
studies. 
 
You can say "yes" or "no" to the following study.  Please mark your choice.   
 
1. 
Future Contact 
I agree to allow my study doctor, or someone approved by my study doctor, to 
contact me regarding future research involving my participation in this study.  
Yes 
No 
 
Where can I get more information? 
 
You may call the National Cancer Institute's Cancer Information Service at:  
 
1-800-4-CANCER (1-800-422-6237) or TTY: 1-800-332-8615 


 
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You may also visit the NCI Web site at http://cancer.gov/ 
 
• For NCI’s clinical trials information, go to: http://cancer.gov/clinicaltrials/ 
 
• For NCI’s general information about cancer, go to http://cancer.gov/cancerinfo/ 
 
You will get a copy of this form.    If you want more information about this study, ask your study 
doctor. 
 
 
Signature 
 
I have been given a copy of all _____ [insert total of number of pages] pages of this form.  I 
have read it or it has been read to me.  I understand the information and have had my questions 
answered.  I agree to take part in this study. 
 
Participant ________________________________ 
 
Date _____________________________________