Clinical trial NCT03533946
Conditions: Prostate Cancer
Sponsor: University of Utah
Start date: 2019-05-20; Completion date: 2023-01-12
Enrollment: 7 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a single arm, open label, phase II trial to assess efficacy of rucaparib.

Detailed description:

Arms: arm 1: Single Arm study, all participants will get rucaparib
Interventions: intervention 1: Rucaparib
Intervention descriptions: intervention 1: Treatment with rucaparib will begin on Cycle 1 Day 1 and continue at 600 mg twice daily. Therapy continues until Prostate Specific Antigen (PSA) progression or intolerable toxicities.

Protocol documents:
ICF_002.pdf: 
Benjamin Maughan, MD PharmD 
 
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Consent and Authorization Document 
A Phase II Study of Rucaparib Monotherapy in Nonmetastatic, Hormone-Sensitive Prostate 
Cancer Demonstrating “BRCAness” Genotype (ROAR) 
 
This document may contain words and information that you do not understand. Please ask your study 
doctor or study staff to explain anything that is not clear to you. You are being asked to take part in a 
research study. Before you decide, it is important for you to understand why the research is being done 
and what it will involve. Please take time to read the following information carefully and discuss it with 
friends and relatives if you wish. Ask the research doctor or staff if there is anything that is not clear or if 
you would like more information. Take time to decide whether or not to volunteer to take part in this 
research study. 
 
 
Once you know about the study, you will make a decision about whether to take part. If you decide to 
take part, you’ll be asked to sign this form. Your decision to take part in this study is voluntary which 
means you are free to decide to join this study or not to join this study.   
 
BACKGROUND 
You are being asked to take part in this study because you have been diagnosed with prostate cancer that 
has a specific type of genetic mutation. The main reason for the study is to see if the drug rucaparib has 
an effect on your prostate-specific antigen (PSA) levels, which can be used to see how effective this 
treatment is on your cancer.  
 
The standard approach to treating your disease is to either begin hormone therapy called androgen 
depravation therapy (ADT) or to carefully monitor and watch your disease. 
 
Rucaparib (Rubraca®) has not been approved by the U.S Food and Drug Administration (FDA) for prostate 
cancer so it is being considered “investigational” for use in this study. An investigational drug is a drug 
that is being tested and is not approved for sale in the United States by the U.S. Food and Drug 
Administration (FDA).  
 
Rucaparib has been approved by the FDA for the treatment of ovarian cancer and is available to be 
prescribed for patients with that disease. 
 
The study is being conducted by Dr. Benjamin Maughan at Huntsman Cancer Institute of the University of 
Utah. 
 
NUMBER OF PARTICIPANTS 
Approximately 15 patients are expected to be enrolled in this study from the Huntsman Cancer 
Institute/University of Utah. 
 
 
 


Benjamin Maughan, MD PharmD 
 
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STUDY PROCEDURES 
If you decide you will take part in the study and you sign this informed consent form, you will have some 
screening tests and procedures done to make sure you are eligible to enroll.  
 
Screening Period 
• 
Medical history will be collected as well as details about what medications and vitamins you are 
currently taking. 
• 
You will have a physical exam and a measure of your vital signs. 
• 
An evaluation of your ability to perform everyday activities will be done. 
• 
If your doctor feels it is necessary, you will have an electrocardiogram (ECG) done. An ECG 
measures the electrical activity of your heart, including the rate and rhythm of your heartbeat. 
• 
You will have a CT (Computerized Tomography) scan as well as a nuclear medicine bone scan. 
These are considered standard of care and would be done even if you were not participating in 
this study.  
• 
You will have your blood drawn and a urine sample taken for standard lab testing to ensure you 
are healthy enough to take part. You will also have blood, urine and any available tissue samples 
taken to check different components of your cancer and blood, including genetics, which will be 
compared to samples that will be collected later.  
• 
If samples are available from a tumor biopsy or cancer surgery in the past, your study doctor will 
request the original tumor samples (this is known as an archived tumor sample) from the medical 
facility where it was performed. They will be looking at genetic components to see if you qualify 
for this study, if this testing has not previously been done.  
 
Treatment Period 
Once it is decided that you are able to enroll into this study, you will begin study treatment. The study 
drug, rucaparib will be given to you in segments of time called “cycles”. For this study, a cycle will be 28 
days. You will take 600 mg orally, twice a day. You should take the tablets with 8 oz. of room temperature 
water, with or without food. These should be taken as close to 12 hours apart as possible, preferably at 
the same times every day. Your doctor and study team will give you more information about your 
treatment plan.  
 
You will come to the clinic on Day 1 of each cycle for various procedures. Some of the procedures are 
being done as part of your routine cancer care. Some are being done because you are participating in this 
study. You will continue on the study treatment until your disease gets worse, you have intolerable side 
effects, you decide to stop, or if your doctor decides it would be in your best interest to stop or the study 
ends.  
 
Study Procedures during the Treatment Period: 
• 
You will have physical exams and measures of your vital signs during your clinic visits, some of 
those will involve a prostate exam. You will also be asked about any changes in medications that 
you are taking and changes in how you are feeling to check for potential side effects. 
• 
Evaluations of your ability to perform everyday activities will be done. 


Benjamin Maughan, MD PharmD 
 
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• 
You will have blood collected for standard lab testing for safety and to test how your cancer is 
responding to treatment. Researchers will also be looking at components of the samples, 
including genetic information, to help them learn about your cancer and how it may change after 
treatment. 
 
 
PSA Progression Confirmation Visit 
If you have confirmed PSA progression at one of your regularly scheduled visits, you may be asked to 
provide Informed Consent for treatment beyond PSA progression. The following tests and procedures 
will be done at this visit. 
 
• 
You will have a physical exam that includes a prostate exam and measures of your vital sign. You 
will also be asked about any changes in medications that you are taking and changes in how you 
are feeling to check for potential side effects. 
• 
An evaluation of your ability to perform everyday activities will be done. 
• 
You will have your blood drawn for safety testing. You will also have blood and urine samples 
taken to check different components, including genetics.  
• 
You will have a CT (Computerized Tomography) scan as well as a nuclear medicine bone scan. 
These are considered standard of care and would be done even if you were not participating in 
this study.  
• 
Optional tissue collection –,If you have disease progression, you may be asked to have an optional 
biopsy for additional tissue collection. Researchers will be looking at components of the samples, 
including genetic information, to help them learn about your cancer and how it may change after 
treatment. This additional biopsy is optional. Please see the end of this form to make your choice 
about participation. 
 
 
End of Treatment 
• 
You will have a physical exam that includes a prostate exam and measures of your vital signs. You 
will also be asked about any changes in medications that you are taking and changes in how you 
are feeling to check for potential side effects. 
• 
An evaluation of your ability to perform everyday activities will be done. 
• 
You will have blood collected for standard lab testing for safety. 
• 
You will have your blood drawn for safety testing. You will also have blood and urine samples 
taken to check different components, including genetics.  
 
Follow-up 
Once you complete your end of treatment visit, you will continue to be followed about every 3 months 
for 2 years. These visits may be conducted via phone call. At these visits, you may have PSA testing 
completed. 
 
 


Benjamin Maughan, MD PharmD 
 
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RISKS 
Rucaparib 
You may have side effects from taking rucaparib or from the procedures used in this study.  Side effects 
may vary from person to person, and can range from mild to very serious.  If you have any side effects as 
a result of taking part in this study, tell your study doctor right away, even if you don’t think they are due 
to the study drug. 
 
Rucaparib (marketed name: Rubraca) is an experimental drug that may have side effects that cannot be 
predicted at this time.  Rare or unknown side effects could possibly occur, including life-threatening events 
or death. If you experience certain side effects, the study doctor may decide to stop or lower your dose 
of study drug until you recover from the side effects. 
 
The following is a list of reported side effects as well as other notable side effects as reported by physicians 
about their patients who are taking rucaparib alone: 
 
Very common (Occurring in ≥ 10% of patients) 
• 
Nausea  
• 
Feeling tired (known as fatigue or lethargy) 
• 
Low blood counts (red blood cells, white blood cells, and platelets).  Sometimes fever occurs 
with low blood counts. These low blood count effects may be more likely to occur after 
multiple cycles of treatment. 
o A low red blood cells count may make you feel tired or dizzy.  If you feel dizzy while 
taking rucaparib, you should avoid potentially hazardous tasks such as driving or 
operating machinery. 
o A low white blood cell count puts you at higher risk for bacterial or viral infections.  
Having a high temperature or fever while your white blood cell count is low is a 
medical emergency and you must proceed to the nearest emergency room as soon 
as possible. 
o A low platelet count affects the ability of your blood to clot and could lead to 
bleeding events. Symptoms include but are not limited to easy bruising, prolonged 
bleeding from cuts, blood in stools or urine, or nose bleeding. 
• 
A low phosphate level in your blood.  Usually there are no symptoms but if the levels are 
critically low, you may notice trouble breathing, confusion, muscle weakness, and/or 
irritability. 
• 
Increase in cholesterol.  If your cholesterol increases significantly, your doctor may prescribe 
a medicine to lower your cholesterol level. 
• 
Changes in kidney and liver function blood tests.  These changes will be evaluated by your 
study doctor along with any other side effects that you are experiencing as well as other test 
results.  
• 
Changes in your sense of taste. 
• 
Stomach-related effects such as constipation, vomiting, diarrhea, decreased appetite, 
stomach pain (epigastric pain), and indigestion.  


Benjamin Maughan, MD PharmD 
 
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• 
Difficulty breathing (dyspnea) 
• 
Dizziness 
• 
Photosensitivity reaction 
o It is possible that rucaparib may make your skin and eyes more sensitive to sunlight. 
You should take all of the usual sun protection precautions when going outside. It is 
advised that you avoid excessive sun exposure, wear protective clothing (including 
wearing a hat and sunglasses), and use sunscreens regularly (sun protection factor 
50 or greater).   
• 
Difficulty sleeping  
 
 
 
Common (Occurring in ≥1 to <10% of patients)  
 
• 
Upper Airway Infection (like the common cold)  
o You may experience infections involving the nose, pharynx, larynx, and sinuses. 
Symptoms include a blocked (congested) nose, a runny nose, and sneezing.  You 
may also have clear discharge (mucus) from the nose.  You may feel generally 
unwell and may also be associated with fever.  Treatment is usually supportive but if 
symptoms persist please inform your doctor. 
 
Uncommon (Occurring in ≥0.1 to < 1% of patients) 
• 
Myelodysplastic syndrome (MDS)a and acute myeloid leukemia (AML)a  
o Effects possibly related to rucaparib, but whose casual link has not yet been formally 
established, have been reported in a very small number of patients treated with 
rucaparib during the safety period (while on treatment with rucaparib and 28 days after 
last dose).  MDS is a pre-cancerous condition where the bone marrow is not as good at 
producing blood cells (red and/or white blood cells and/or platelets).  People with MDS 
need transfusions (red blood cells and/or platelets) and/or other treatments.  In some 
cases, MDS can progress to AML, which is a cancer of the bone marrow where more 
abnormal and immature white blood cells (also called blasts) are made than normal 
white blood cells.  People with AML need treatment with chemotherapy and/or a bone 
marrow transplant.  Patients may develop AML without first being diagnosed with MDS. 
o Events of MDS and AML have also been reported with PARP inhibitors similar to 
rucaparib.  At this time it is not known whether rucaparib or other PARP inhibitors cause 
MDS or AML, or if these developed as a result of previous chemotherapy these patients 
received.  Your study doctor will closely monitor your blood cell levels during treatment.  
If he/she has any concerns about your blood counts you may be asked to have a biopsy 
of your bone marrow. 


Benjamin Maughan, MD PharmD 
 
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Allergic Reactions 
As with any drug, it is possible that you could have allergic reactions to study drug, such as itching, skin 
rash, facial swelling, and/or a severe or sudden drop in blood pressure.  A sudden drop in blood pressure 
could lead to shock with loss of consciousness and/or possible seizures, including the possibility of 
death.  If you have any of the above symptoms, seek medical attention right away. 
 
REPRODUCTIVE RISKS 
It is unknown if rucaparib has an effect on semen. Because of this, you must practice abstinence or use a 
condom to avoid passing rucaparib to your partner with all sexual activity. You should not father a baby 
or donate sperm while you are in this study and for at least 6 months after you are off treatment. If your 
partner is of childbearing potential, you must use (or have her use) an effective contraceptive while on 
the study and for 6 months after the last dose. Examples of medically acceptable birth control include 
medically prescribed IUDs, oral pill, skin patch, vaginal ring or injectable hormonal contraceptives. Please 
ask the study team for more information about these options.   
If you think that you have fathered a baby while receiving treatment or within 6 months of completing 
treatment in this study, you should inform your doctor immediately.    
 
Other Risks and Inconveniences including Genetic Risks 
There are also non-physical risks associated with taking part in this study, such as the risks associated with 
a breach of privacy or confidentiality.  For example, if your identity as a participant in genetic research or 
your identifiable genetic or health information were disclosed to unauthorized persons, there is the 
possible risk of discrimination by employers or insurance providers. The risks of such improper disclosure 
are very small because Huntsman Cancer Institute has adopted strict privacy and confidentiality 
procedures for this research.  
 
Blood draws or IV: Risks associated with drawing blood or putting a needle in your vein might include pain 
from the puncture, bruising, bleeding, infection, or fainting. Every effort will be made to minimize 
discomfort. 
 
Risk of Biopsy: Tumor biopsies may cause pain, bruising, bleeding, redness, low blood pressure, swelling, 
and/or infection at the site of the biopsies.  An allergic reaction to the anesthetic may occur.  A scar may 
form at the biopsy site. 
 
UNFORESEEABLE RISKS 
Problems or side effects that are not known could also occur. Most side effects are expected to go away 
after treatment is stopped or interrupted; however in some cases the side effects may be serious, long-
lasting, permanent or lead eventually to death.  
 
 
What are the Uses for my Samples Collected During the Study  
Your participation in genetic testing is a mandatory part of this study. It will be performed in order to 
learn more about factors which may predict response to the study treatments.  


Benjamin Maughan, MD PharmD 
 
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Segments of the DNA called genes are responsible for passing particular traits such as eye color from 
parents to children.   
 
In the United States, the Genetic Information Nondiscrimination Act of 2008 (GINA) prohibits 
discrimination in health coverage and employment based on genetic information. GINA, together with the 
Health Insurance Portability and Accountability Act (HIPAA), generally prohibits health insurers or health 
plan administrators from requesting or requiring genetic information of an individual or the individual’s 
family members, or using it for decisions regarding coverage, rates, or preexisting conditions. The law also 
prohibits most employers from using genetic information for hiring, firing, or promotion decisions, and 
for any decisions regarding terms of employment. Utah State Law also offers protection against 
discrimination in health coverage and employment.  
 
You will not receive any of your genetic information that comes from the testing in this study, nor will it 
become a part of your medical record. The results will be kept on password-protected computers and 
results will be accessible only to the investigator and other authorized people. 
 
BENEFITS 
There may not be any benefit to you from your being in the study. The information gained in this study 
will aid in the understanding of cancer and help in the development of new approaches to its treatment 
in the future. 
 
ALTERNATIVE PROCEDURES 
You do not have to be in this study to get help for the type of cancer you have.  The study doctor will talk 
to you about other things you can do for this type of cancer, including the important risks and benefits.   
 
Some other things you might do are: 
• 
Use other approved chemotherapy regimens. 
• 
Use other investigational treatments. 
• 
Get supportive care.  
• 
Choose to have no further treatment.  
 
PERSON TO CONTACT 
If you have questions, complaints or concerns about this study, you can contact Dr. Benjamin Maughan at 
801-585-0255. If you think you may have been injured from being in this study, please call Dr. Maughan 
at 801-585-0255. The University Hospital Operator can be reached at this number: 801-581-2121 available 
24-hours a day.  Please ask for the oncologist on call.  
 
Institutional Review Board: Contact the Institutional Review Board (IRB) if you have questions regarding 
your rights as a research participant. Also, contact the IRB if you have questions, complaints or concerns 
which you do not feel you can discuss with the investigator. The University of Utah IRB may be reached 
by phone at (801) 581-3655 or by e-mail at irb@hsc.utah.edu.   


Benjamin Maughan, MD PharmD 
 
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Research Participant Advocate:  You may also contact the Research Participant Advocate (RPA) by 
phone at (801) 581-3803 or by email at participant.advocate@hsc.utah.edu.  
 
RESEARCH-RELATED INJURY 
If you are injured from being in this study, medical care is available to you at the University of Utah, as it 
is to all sick or injured people. The University of Utah has not set aside any money to pay the costs for 
such care. The University will work with you to address costs from injuries. Costs would be charged to 
you or your insurance company (if you have insurance), to the study sponsor or other third party (if 
applicable), to the extent those parties are responsible for paying for medical care you receive. Since 
this is a research study, some health insurance plans may not pay for the costs. By signing this consent 
form you are not giving up your right to pursue legal action against any parties involved with this 
research. 
The University of Utah is a part of the government. If you are injured in this study, and want to sue the 
University or the doctors, nurses, students, or other people who work for the University, special laws 
may apply. The Governmental Immunity Act of Utah is a law that controls when a person needs to bring 
a claim against the government, and limits the amount of money a person may recover. See sections 
63G -7-101 to -904 of the Utah Code. 
 
VOLUNTARY PARTICIPATION 
Taking part in this research study is voluntary.  You may decide not to take part or you may leave the study 
at any time.  Refusal to take part or the decision to withdraw from this study will involve no penalty or 
loss of benefits to which you are otherwise entitled.  
 
Tell the study doctor if you are thinking about stopping or decide to stop, as it may be necessary to do 
certain tests in order to ensure your safety.  If you choose not to return for an assessment, we may ask 
for medical records from your current general practitioner in order to continue to monitor your health.   
 
If you decide not to continue in the study at any time, your study doctor will arrange for you to receive 
alternative treatment and any necessary assessments or procedures according to standard of care.   
 
RIGHT OF INVESTIGATOR TO WITHDRAW 
Your study doctor may decide to take you off this study at any time without your consent for any of the 
following reasons: 
• 
if your disease becomes worse and is not responding to the study drug, 
• 
if he or she believes it is in your best interest, 
• 
if you do not follow the study rules, 
• 
if you miss study visits and/or procedures, 
• 
if you have serious side effects, 
• 
if you become pregnant, 
• 
you do not later consent to any future changes that may be made in the study plan; or any other 
reason. 


Benjamin Maughan, MD PharmD 
 
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There is also the possibility that the investigator, may close the study before your participation is complete 
and without prior warning.  If any of these events were to happen, your study doctor would assist with 
arrangements for your continued care as appropriate. 
 
COSTS AND COMPENSATION TO PARTICIPANTS 
Some of the procedures and treatments you’ll have while you are on the study are considered “standard 
of care” for your type of illness. Even though you will be a part of the study, these types of   procedures 
and treatments will be billed to you and/or your insurance company just like regular medical care. Some 
procedures and treatments you’ll have while you are on the study are considered “study related” and are 
not billed to you and your insurance company. You should ask your study coordinator and treating 
physician for details about the specific procedures you or your insurance company will be financially 
responsible for. 
Clovis, the manufacturer of rucaparib, will be supplying the study drug to you free of charge in this study.  
 
You may be eligible for assistance with costs associated with travel for purposes of research participation. 
Please speak with your study coordinator or physician for details.  If eligible, you may be asked to provide 
receipts in order to receive reimbursement. It will be necessary for us to collect your Social Security 
Number for your reimbursement.  You will need to provide this information on a Federal W-9 Form that 
is filed with our accounts payable department.  No other information (e.g. the name of this study) will be 
provided to that office.  This amount will not be reported to the Internal Revenue Service (IRS). 
 
NEW INFORMATION 
You will be given any new information about the study drugs that may affect your willingness to start or 
continue in the study as it becomes available. You will not receive any results from the genetic testing 
performed in this study. The results will also not be included as part of your medical records.  
 
AUTHORIZATION FOR USE OF YOUR PROTECTED HEALTH INFORMATION  
Signing this document means you allow us, the researchers in this study, and others working with us to 
use some information about your health for this research study. 
 
This is the information we will use and include in our research records: 
• 
Demographic and identifying information like your name, address, telephone number, and email 
address. 
• 
Related medical information about you like family medical history, allergies, current and past 
medications or therapies, information from physical examinations such as blood pressure 
readings, heart rate, temperature, and lab results.  
• 
All tests and procedures that will be done in the study. 
 
 
 
 
How we will protect and share your information: 


Benjamin Maughan, MD PharmD 
 
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We will do everything we can to keep you information private, but we cannot guarantee this. The research 
records will be kept in a secured manner and computer records will be password protected. We may need 
to disclose information about you as required by law. 
Study information may be stored with other information in your medical record. Other doctors, nurses, 
and third parties (like insurance companies) may be able to see this information as part of the regular 
treatment, payment, and health care operations of the hospital.  
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law.  This Web site will not include information that can identify you.  At most, the Web site will include 
a summary of the results.  You can search this Web site at any time. 
 
In order to conduct this study and make sure it is conducted as described in this form, the research records 
may be used and reviewed by others who are working with us on this research: 
• 
Members of the research team and University of Utah Health Sciences Center 
• 
The University of Utah Institutional Review Board (IRB), who reviews research involving people to 
make sure the study protects your rights; 
• 
Clovis, the manufacturer of rucaparib, and their affiliates 
• 
Government agencies responsible to confirm research accuracy such as the United States Food 
and Drug Administration (FDA), and the National Cancer Institute (NCI) which is a part of the 
National Institute of Health (NIH)  
• 
Governmental agencies in other countries where the study drug may be considered for approval.  
 
If we share your identifying information with groups outside of the University of Utah Health Sciences 
Center, the groups may not be required to follow the same federal privacy laws that we follow. They may 
also share your information again with others not described in this form.  
 
What if I decide not to take part after I sign the Consent and Authorization Form? 
You can tell us anytime that you do not want to be in this study and do not want us to use your health 
information. You can also tell us in writing. If you change your mind, we will not be able to collect new 
information about you, and you will be withdrawn from the research study. However, we can continue to 
use information we have already started to use in our research, as needed to maintain the integrity of the 
research. 
 
This authorization does not have an expiration date. 
 
You have a right to information used to make decisions about your health care. However, your information 
from this study will not be available during the study; it will be available after the study is finished. 
 
 
 
 
 
Optional Biopsy for Research 


Benjamin Maughan, MD PharmD 
 
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Researchers would like for you to have an optional tumor biopsy to collect tissue if you experience disease 
progression while on study treatment. You do not have to participate in this optional study component. 
If you choose to participate in the optional tumor biopsy and tissue collection, you will have a tumor 
biopsy taken at the time of disease progression. This tumor tissue will be used for research related to this 
study only. If you choose not to participate in the biopsy sample part of the study, your decision will not 
exclude you from the main study. Please initial and date the corresponding line below to let us know if 
you would like to participate: 
 
________ 
I do want to participate in the optional tumor tissue collection. 
 
 
________ 
I do not want to participate in the optional tumor tissue collection.   
 
FUTURE USE OF SAMPLES 
If you agree, the study team would like to save any leftover samples to bank it for future unspecified 
cancer related research (tissue banking). This testing may include genetic testing. The tissue bank will be 
managed here at HCI by the Biorepository and Molecular Pathology (BMP) department and will be kept 
by them. Participation in tissue banking is completely optional. Your samples will be stored with the 
following information: type of specimen, diagnosis, sex, age, treatment, and treatment response. Only 
the study doctor and the study staff, including those who manage the tissue bank at the BMP, will have 
access to those identifiers. Any lab that does testing outside of HCI will not receive these identifiers. You 
do not have the option to have your samples de-identified. If this is not acceptable to you, you should 
not participate in the optional specimen banking portion of the study. All information obtained from 
your samples will be kept confidential as stated in the AUTHORIZATION FOR USE OF YOUR PROTECTED 
HEALTH INFORMATION section of this form.  
 
At any time, you may ask that your samples not be used for future research and that they be destroyed 
by contacting the study doctor and/or study team. If you ask for this, study tests will be done, but 
samples will not be used for future research testing. However, any information collected from your 
samples before your request to destroy them will be kept by HCI.   
 
If you decide to stop taking part in the study, but do not request that your samples be destroyed, HCI 
and its authorized representatives may continue to use your samples for future research and genetic 
testing. 
 
Because the results from future research will not directly affect your health care, we will not share the 
results from future studies with you or your doctors.  
 
Samples obtained from you in this research may help in the development of a commercial product by 
the investigator or the benefactor or its research partners. There are no plans to provide financial 
compensation to you should this occur. 
Banking for Future Use 


Benjamin Maughan, MD PharmD 
 
Page 12 of 14 
IRB# 111833 IIT ROAR 
Consent Version: 09JUL2021 
Previous Version: 26MAR2021 
 
FOOTER FOR IRB USE ONLY 
Version: K1315 
 
 
University of Utah 
Institutional Review Board 
Approved 8/25/2021 
Expires 4/14/2022 
IRB_00111833 
 
 
Researchers would like to save any of your left over samples for future unspecified cancer research as 
described above. If you choose not to participate in the tissue banking part of the study, your decision 
will not exclude you from the main study. Please initial and date the corresponding line below to let us 
know if you would like to participate: 
 
initial______   /date___________ I do want to participate in the optional tissue banking. 
 
initial______   /date____________ I do not want to participate in the optional tissue banking. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Benjamin Maughan, MD PharmD 
 
Page 13 of 14 
IRB# 111833 IIT ROAR 
Consent Version: 09JUL2021 
Previous Version: 26MAR2021 
 
FOOTER FOR IRB USE ONLY 
Version: K1315 
 
 
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Institutional Review Board 
Approved 8/25/2021 
Expires 4/14/2022 
IRB_00111833 
 
 
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questions. I will be given a signed copy of the consent and authorization form to keep. 
 
I agree to take part in this research study and authorize you to use and disclose health information 
about me for this study, as you have explained in this document. 
 
 
_________________________________________ 
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and complete interpretation of the exchange between the research staff member named above and the 
patient named above, to the best of my ability. 
 
                     
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Benjamin Maughan, MD PharmD 
 
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IRB# 111833 IIT ROAR 
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Prot_SAP_000.pdf: 
Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
Principal Investigator: Benjamin Maughan, MD, PharmD 
A Phase II Study of Rucaparib Monotherapy in Nonmetastatic, 
Hormone-Sensitive Prostate Cancer Demonstrating 
“BRCAness” Genotype (ROAR) 
CTO ID # HCI-17-GU-24 – Lead Trial ID # HCI111833 – NCT03533946 
Coordinating Center 
Huntsman Cancer Institute 
Principal Investigator 
Benjamin Maughan, MD, PharmD 
Huntsman Cancer Institute - University of Utah 
2000 Circle of Hope 
Salt Lake City, UT 84112 
Phone 801-213-6147 
Email: Benjamin.Maughan@hci.utah.edu 
Statistician 
Kenneth M. Boucher, PhD  
Statistician 
Research Associate Professor, Internal Medicine 
Huntsman Cancer Institute - University of Utah 
2000 Circle of Hope Room 1710 
Email: Kenneth.Boucher@hci.utah.edu 
Medical Monitor 
Andrew Harris 
Huntsman Cancer Institute - University of Utah 
2000 Circle of Hope 
Salt Lake City, UT 84112 
Phone 801-213-6147 
Email: Andrew.Harris@hsc.utah.edu 
Cordinating Center Site Contact 
Please contact your assigned Clinical Site Monitor 
and the Clinical Trials Compliance Office 
2000 Circle of Hope 
Salt Lake City, UT 84112 
HCI-RCO@utah.edu 
Drug Manufacturer  
Clovis Oncology Inc.  
Contact: Kate Ryan, PhD,  
Medical Science Liaison Clovis Oncology 
Phone: 541-280-8311, 
Email: kryan@clovisoncology.com 
NCT Number (CT.gov) 
NCT03533946 


Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
Page 2 of 52 
Drug Manufacturer Protocol ID 
338-IIT-086 
Investigational agent 
Rucaparib 
IND Number 
Exempt 
 
 
Historical Protocol Versions 
Version 1: 28JUN2018 
Version 2: 12SEP2018 
Version 3: 19MAR2019 
Version 4: 29JAN2020 
Version 5: 26MAR2021 
Version 6: 09JUL2021 
 
 


Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
Page 3 of 52 
TABLE OF CONTENTS 
Page 
TABLE OF CONTENTS ................................................................................................................ 3 
LIST OF ABBREVIATIONS ......................................................................................................... 5 
PROTOCOL SIGNATURE ............................................................................................................ 8 
STUDY SUMMARY...................................................................................................................... 9 
1 
OBJECTIVES ....................................................................................................................... 11 
1.1 
Primary Objective and Endpoint ................................................................................ 11 
1.2 
Secondary Objectives and Endpoint ........................................................................... 11 
1.3 
Exploratory Objectives and Endpoint ......................................................................... 11 
2 
BACKGROUND .................................................................................................................. 11 
3 
DRUG INFORMATION ...................................................................................................... 13 
3.1 
Rucaparib .................................................................................................................... 13 
4 
STUDY DESIGN.................................................................................................................. 19 
4.1 
Description.................................................................................................................. 19 
4.2 
Number of Patients ..................................................................................................... 19 
4.3 
Number of Study Centers ........................................................................................... 20 
4.4 
Study Duration ............................................................................................................ 20 
5 
ELIGIBILITY CRITERIA .................................................................................................... 21 
5.1 
Inclusion Criteria ........................................................................................................ 21 
5.2 
Exclusion Criteria ....................................................................................................... 22 
6 
TREATMENT PLAN ........................................................................................................... 24 
6.1 
Administration Schedule ............................................................................................ 24 
6.2 
Rucaparib Treatment .................................................................................................. 24 
6.3 
Concomitant Medications ........................................................................................... 25 
6.4 
Duration of Therapy ................................................................................................... 26 
7 
TOXICITIES AND DOSAGE MODIFICATION ............................................................... 28 
7.1 
Dose Modifications..................................................................................................... 28 
7.2 
Contraception.............................................................................................................. 30 
7.3 
Supportive Care .......................................................................................................... 31 
8 
STUDY CALENDAR .......................................................................................................... 32 
9 
STUDY PROCEDURES ...................................................................................................... 35 
9.1 
Screening .................................................................................................................... 35 
9.2 
On-Treatment Evaluations (Day 1 of each cycle) ...................................................... 35 
9.3 
PSA Progression Confirmation Visit .......................................................................... 36 
9.4 
End of Treatment ........................................................................................................ 36 
9.5 
Follow-up Evaluations Q 90 days (± 14 days) ........................................................... 37 
10 CRITERIA FOR EVALUATION AND ENDPOINT .......................................................... 37 
10.1 
Efficacy ....................................................................................................................... 37 
10.2 
Safety .......................................................................................................................... 37 
10.3 
Stopping Rules ............................................................................................................ 38 
11 STATISTICAL CONSIDERATIONS.................................................................................. 38 
11.1 
Primary Objective ....................................................................................................... 38 
11.2 
Secondary Objectives ................................................................................................. 38 
11.3 
Exploratory Objectives ............................................................................................... 38 


Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
Page 4 of 52 
12 REGISTRATION GUIDELINES ......................................................................................... 39 
13 DATA SUBMISSION SCHEDULE .................................................................................... 39 
14 SPECIAL INSTRUCTIONS ................................................................................................ 39 
14.1 
Correlative Studies ..................................................................................................... 39 
15 ETHICAL AND REGULATORY CONSIDERATIONS .................................................... 41 
15.1 
Informed consent ........................................................................................................ 41 
15.2 
Human Subjects Protections ....................................................................................... 41 
15.3 
Institutional Review .................................................................................................... 41 
15.4 
Adverse Events / Serious Adverse Events .................................................................. 42 
15.5 
SAE Reporting Requirements .................................................................................... 44 
15.6 
Reporting of Pregnancy .............................................................................................. 45 
15.7 
Protocol Amendments ................................................................................................ 45 
15.8 
Protocol Deviations .................................................................................................... 45 
15.9 
FDA Annual Reporting .............................................................................................. 45 
15.10 
Clinical Trials Data Bank ........................................................................................... 46 
15.11 
Record Keeping .......................................................................................................... 46 
16 BIBLIOGRAPHY ................................................................................................................. 47 
Appendix A — Rucaparib Dosing Diary ...................................................................................... 49 
Appendix b – Prostate Cancer Clinical Trials Working Group 3 (PCWG3) ................................ 51 
 
 
 


Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
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LIST OF ABBREVIATIONS 
Abbreviation or Term1 
Definition/Explanation 
AE 
Adverse event 
AESI 
Adverse events of special interest 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
APTT 
Activated partial thromboplastin time 
AST 
Aspartate aminotransferase 
AV 
Atrioventricular 
β-HCG 
Beta-human chorionic gonadotropin 
BID 
Twice daily 
BLQ 
Below limit of quantification 
BMI 
Body mass index 
BP 
Blood pressure 
BUN 
Blood urea nitrogen 
Ca++ 
Calcium 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
CHF 
Congestive heart failure 
CI 
Confidence interval 
Cl- 
Chloride 
CLcr 
Creatinine clearance 
Cmax 
Maximum observed concentration 
Cmin 
Trough observed concentration 
CNS 
Central nervous system 
CR 
Complete response 
CRF 
Case report form 
CT 
Computed tomography 
CTCAE 
Common Toxicity Criteria for Adverse Events 
CV 
Coefficient of variation 
CYP 
Cytochrome P450 
D/C 
Discontinue 
ECOG 
Eastern Cooperative Oncology Group 


Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
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Abbreviation or Term1 
Definition/Explanation 
eCRF 
Electronic case report form 
DLT 
Dose Limiting Toxicity 
ECG 
Electrocardiogram 
Eg 
Exempli gratia (for example) 
FACS 
Fluorescence Activated Cell Sorting  
FDA 
Food and Drug Administration 
FDG-PET 
Fluorodeoxyglucose (FDG)-positron emission tomography 
(PET) 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GGT 
Gamma glutamyl transferase 
GLP 
Good laboratory practice  
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCO3- 
Bicarbonate 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
HR 
Heart rate 
hr 
Hour or hours 
IC50 
Half maximal inhibitory concentration 
i.e. 
Id est (that is) 
IEC 
Independent ethics committee 
INR 
International normalized ratio 
IRB 
Institutional review board 
IU 
International unit 
IV 
Intravenous, intravenously 
LDH 
Lactate dehydrogenase 
LLQ 
Lower limit of quantitation 
MedRA 
Medical Dictionary for Drug Regulatory Activities 
MRI 
Magnetic resonance imaging 
MRSD 
Maximum recommended starting dose 
MTD 
Maximum tolerated dose  
NOAEL 
No-observed-adverse-effect level 
NOEL 
No-observed-effect-level 


Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
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Abbreviation or Term1 
Definition/Explanation 
PD 
Pharmacodynamic(s) 
PFS 
Progression Free Survival 
PK 
Pharmacokinetic(s) 
PO 
Per os (administered by mouth) 
PR 
Partial response 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
QC 
Quality control 
RBC 
Red blood cell 
QD 
Once daily 
QTc 
QT interval corrected  
QTcF 
QT interval corrected using Fredericia equation 
SAE 
Serious adverse event 
SD 
Standard deviation or stable disease 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
T1/2 
Terminal elimination half-life 
T3 
Triiodothyronine 
T4 
Thyroxine 
Tmax 
Time of maximum observed concentration 
TID 
Three times daily 
TSH 
Thyroid-stimulating hormone 
ULN 
Upper limit of normal 
ULQ 
Upper limit of quantitation 
UV 
Ultraviolet 
WBC 
White blood cell 
WOCBP 
Women of childbearing potential 
WONCBP 
Women of nonchildbearing potential 
1 All of these abbreviations may or may not be used in protocol.  
 
 


Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
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PROTOCOL SIGNATURE 
I confirm that I have read this protocol, and I will conduct the study as outlined herein and 
according to the ethical principles stated in the latest version of the Declaration of Helsinki, the 
applicable ICH guidelines for good clinical practice, and the applicable laws and regulations of the 
federal government. I will promptly submit the protocol to the IRB for review and approval. Once 
the protocol has been approved by the IRB, I understand that any modifications made during the 
course of the study must first be approved by the IRB prior to implementation except when such 
modification is made to remove an immediate hazard to the subject. 
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure that they 
are fully informed regarding the study treatment, the conduct of the study, and the obligations of 
confidentiality. 
Note: This document is signed electronically through submission and approval by the Principal 
Investigator in the University of Utah IRB Electronic Research Integrity and Compliance 
Administration (ERICA) system. 
 
 


Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
Page 9 of 52 
STUDY SUMMARY 
Title 
A Phase II Study of Rucaparib Monotherapy in Nonmetastatic, 
Hormone-Sensitive Prostate Cancer Demonstrating “BRCAness” 
Genotype. 
Short Title 
Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Protocol Number 
IRB# 111833 
IND 
Exempt 
Phase 
Phase II 
Design 
This is a single arm, open label, phase II trial to assess efficacy of 
rucaparib. 
Study Duration 
Expected enrollment duration is 12 months, patients will remain 
on study treatment until PSA progression defined by PCWG322. 
We estimate 2-3 years for total study duration. 
Study Center(s) 
This study will be conducted at the Huntsman Cancer Institute. 
Objectives 
Primary Objective:  
To assess PSA progression free survival (PSA-PFS) . Patients 
will have PSA values measured every month.  
Secondary Objectives  
1. To assess the safety of rucaparib. 
2. To assess the proportion of patients with a 50% reduction in 
PSA levels (PSA50) compared to the baseline value 
3. To assess the proportion of patients with an undetectable PSA 
after initiation of PARP therapy. 
Number of Subjects 
15 evaluable subjects will be enrolled 
Diagnosis and Main 
Eligibility Criteria 
1. Histologically proven adenocarcinoma of the prostate with 
BRCAness (defined as an alteration in one or more of the 
following genes: BARD1, BRCA1, BRCA2, BRIP1, CHEK1, 
CHEK2, FANCA, NBN,  PALB2, RAD51C, RAD51D,  
RAD51, RAD51B based on soft tissue or liquid biopsy. 
2. Rising PSA without radiographic evidence of metastatic 
disease and with PSA doubling time of ≤10 months. 
3. ECOG/Zubrod score of 0-2. 
4. Subject must not have received any prior systemic therapy for 
prostate cancer unless used in the context of definitive 
treatment for prostate cancer. Patients may have not received 
ADT treatment for longer than 24 months. 
Study Product, Dose, 
Route, Regimen 
Rucaparib 600mg orally twice daily 
No patients will be on ADT therapy either by surgical castration 
or with GnRH agonist or antagonist or on androgen synthesis 
blocker or androgen receptor antagonists during the study period. 
Duration of administration Subjects will remain on study treatment until unacceptable 
toxicity, PSA progressive disease (unless they meet the criteria 
for continued treatment post-progression as defined by section 
6.4.1), or patient withdrawal. 


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Version Date: 09JUL2021 
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Reference therapy 
None 
Statistical Methodology 
Primary Objective: The total sample size is 15 patients. The null 
hypothesis is that median PSA-PFS is 3 months.  With an 
alternative hypothesis that median PSA-PFS is 12 months, a 
sample size of 15 provides 90% power at one-sided alpha = 0.05. 
The proportion of subjects who achieve PSA50 will be reported 
along with a 95% exact binomial confidence interval. 
Descriptive analysis methods will be used to analyze tabulated 
safety characteristics. Kaplan-Meier methods will be used to 
assess the proportion of patients with an undetectable PSA after 
initiation of PARP therapy. 
 
 


Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
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1 OBJECTIVES 
1.1 
Primary Objective and Endpoint 
 To assess PSA progression-free survival (PSA-PFS).  
Endpoint: the levels of PSA will be monitored monthly for comparison to baseline 
levels until the time of PSA progression, as defined by Prostate Cancer Working 
Group 3 (PCWG3)22 criteria (See Appendix B). 
1.2 
Secondary Objectives and Endpoint 
 To assess the safety of rucaparib in patients with biochemically recurrent hormone-
sensitive prostate cancer. 
Endpoint: adverse events will be monitored regularly during patient enrollment and 
follow up to assess the toxicity of rucaparib using validated CTCAE v5.0 criteria. 
 To assess the proportion of patients with a 50% reduction in PSA levels (PSA50) 
compared to the baseline value at the time of study enrollment. 
Endpoint: the levels of PSA will be monitored monthly for comparison to baseline 
levels. 
 To assess the proportion of patients with an undetectable PSA after initiation of 
PARP therapy at 6 and 12 months. 
Endpoint: the levels of PSA will be monitored monthly for comparison to baseline 
levels to determine when PSA becomes undetectable.  
 To evaluate overall survival (OS) in nonmetastatic hormone-sensitive prostrate cancer 
patients treated with rucaparib.  
Endpoint: Subjects will be evaluated for survival using Kaplan-Meier estimation. 
1.3 
Exploratory Objectives and Endpoint 
 To evaluate exploratory biomarkers predictive of response and resistance to treatment 
with rucaparib. 
Endpoint: blood and other tissue will be collected at baseline and during treatment to 
correlate clinical responses with various potentially predictive biomarkers.  
 To evaluate concordance between PSA-PFS and radiographic progression 
Endpoint: levels of PSA will be monitored monthly and compared to the detection of 
any measureable new lesions by radiographic detection.  
2 BACKGROUND 
For decades, hormonal therapy using gonadotropin releasing hormone agonists/antagonists or 
surgical castration have been the first-line treatment in patients with metastatic hormone-
sensitive prostate cancer. Androgen deprivation therapy (ADT) has repeatedly been shown to be 
effective in palliating symptoms and in prolonging survival for patients.1 This is not curative 
therapy, so invariably patients will progress on ADT and develop metastatic castration-resistant 


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Version Date: 09JUL2021 
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prostate cancer. Common practice is to continue with ADT despite progression. All of the 
subsequent treatments including abiraterone,2 enzalutamide,3 chemotherapy4 and radium5 have 
been tested in conjunction with ADT. With improved treatments for metastatic prostate cancer, 
patients are often surviving longer, with a median overall survival of approximately 5 years for 
patients with metastatic disease at diagnosis6 to over 8 years for patients progressing to 
metastatic disease after definitive local treatment.7 The long-term adverse effects of continued 
androgen deprivation therapy are becoming more apparent and clinically important with 
improved disease control. ADT increases the risk for cardiovascular disease, osteoporosis and 
metabolic syndrome.8 Finding treatment strategies that control prostate cancer and delay ADT 
use can further improve the care of patients with prostate cancer by both directly controlling 
metastatic disease progression, and preventing the health complications of long-term ADT use.  
Prostate cancer patients with DNA repair defects are an important population of prostate cancer. 
A common term used for these genomic alterations associated with DNA repair gene defects is 
“BRCAness”.9 The estimated incidence of BRCAness is 12-19% in prostate cancer.10,11 This 
population generally has more aggressive disease and therefore a worse overall prognosis 
compared to men without BRCAness. Men with BRCAness prostate cancer often get diagnosed 
with prostate cancer earlier, and develop metastatic disease earlier compared to those who do not 
harbor BRCAness. Furthermore, BRCAness may portend a poor prognosis, including a poor 
overall survival.12,13 The risk of disease progression to metastatic disease is significant in patients 
with BRCAness prostate cancer. The percentage of BRCAness patients free from metastatic 
disease was 90%, 72%, and 50% at 3, 5, and 10 years, respectively, compared to 97%, 94%, and 
84% at 3, 5 and 10 years for patients with intact DNA repair (p < 0.001).14 
Treatment using PARP inhibitors along with ADT in this population has demonstrated 
significant clinical activity.15 In the seminal study, 50 patients with castration-resistant prostate 
cancer were enrolled regardless of BRCAness status and treated with olaparib, a PARP inhibitor. 
These patients were resistant to many prior therapies including docetaxel, abiraterone, or 
enzalutamide and many had been treated with cabazitaxel as well. 49 patients were evaluable for 
response. Sixteen patients demonstrated a response, including 4 patients with a durable response 
(treatment ≥ 12 months). 16 of the 49 patients were positive for BRCAness. 14 out of the 16 
(88%) biomarker-positive patients had a composite response to olaparib, rather than a RECIST 
evaluable response. Only 2 of 33 (6%) biomarker-negative patients experienced a response. This 
strongly suggests significant clinical activity of PARP therapy in patients with BRCAness.  
Given debilitating physical and psychological side effects of ADT in relatively younger men 
with BRCAness prostate cancer, delaying ADT in these men may be an attractive strategy. Given 
the proven efficacy of PARP inhibitors in the CRPC setting, PARP inhibitor monotherapy has 
the potential to result in PSA responses, and delay onset of metastatic disease. 
We hypothesize that treatment with PARP inhibitor monotherapy in men with high risk 
biochemically recurrent prostate cancer (i.e., PSA only relapse with no radiographic evidence of 
disease with a PSA doubling time of < 9 months) will result in acceptable disease control in 
terms of PSA response, allow delay of androgen deprivation therapy, and delay the onset of 
metastasis. 


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3 DRUG INFORMATION 
3.1 
Rucaparib 
Rucaparib (CO-338) is a small molecule inhibitor of poly (adenosine diphosphate [ADP]-
ribose) polymerase (PARP) being developed for the treatment of cancer associated with 
homologous recombination deficiency (HRD). Rucaparib has been shown to potently inhibit 
PARP-1, PARP-2, and PARP-3 and has demonstrated activity in cells, animal models and 
patients with a breast cancer gene 1 or 2 (BRCA1 and BRCA2) mutations in both clinical and 
nonclinical studies. 
Clovis Oncology, Inc. (Clovis) is developing rucaparib for oral administration in patients 
with advanced ovarian cancer and metastatic castration-resistant prostate cancer (mCRPC) 
associated with HRD, including patients with a deleterious mutations in BRCA1, BRCA2, 
and other HR gene mutations. 
 Summary of Nonclinical Experience with Rucaparib 
An overview of data from nonclinical and clinical studies with rucaparib are summarized 
below. Further detail is provided in the most recent rucaparib Investigator’s Brochure (IB).  
Pharmacological assessment demonstrated that rucaparib is a potent and selective inhibitor of 
PARP-1, PARP-2, and PARP-3 and has robust and durable in vitro and in vivo activity in 
multiple BRCA1/2 mutant cell lines and xenograft models. Rucaparib was also active in a 
BRCA wild-type model, consistent with in vitro data suggesting that rucaparib is active in 
cells with other defects in homologous recombination through synthetic lethality. In vitro 
screens suggested that rucaparib has a limited potential for off-target effects. Safety 
pharmacology studies suggest that when given orally, rucaparib poses a low risk for causing 
neurobehavioral and cardiac effects in patients.  
In pharmacokinetic (PK) studies, rucaparib demonstrated species-dependent oral 
bioavailability, moderate plasma protein binding, and large volumes of distribution in 
nonclinical species. As a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) 
substrate, rucaparib demonstrated minimal penetration of rucaparib-derived radioactivity 
through the blood-brain barrier.  
In vitro data suggested slow metabolism by cytochrome P450 (CYP) enzymes, with CYP2D6 
and to a lesser extent CYP1A2 and CYP3A4 contributing to the metabolism of rucaparib. 
Rucaparib was mainly excreted in feces in rats and dogs. In vitro, rucaparib reversibly 
inhibited CYP1A2, CYP2C19, CYP2C9, and CYP3A, and to a lesser extent CYP2C8, 
CYP2D6, and UDP-glucuronosyltransferase 1A1 (UGT1A1). Rucaparib induced CYP1A2, 
and down-regulated CYP2B6 and CYP3A4 in human hepatocytes at clinically relevant 
exposures. Rucaparib is a potent inhibitor of multidrug and toxin extrusion protein 1 
(MATE1) and MATE2-K, a moderate inhibitor of organic cationic transporter 1 (OCT1), and 
may inhibit P-gp and BCRP in the gut. 
Oral dosing of rucaparib in single and repeat dose toxicity studies in rats and dogs resulted in 
toxicity to the hematopoietic, lymphopoietic, and gastrointestinal systems. These toxicities 
were generally both reversible upon recovery and predictive of toxicities observed in 
patients. Rucaparib was shown to be clastogenic in an in vitro chromosomal aberration assay 
suggesting potential genotoxicity in humans. Reproductive and development toxicity studies 


Short Title: Rucaparib Nonmetastatic prOstAte with BRCAness (ROAR) 
Version Date: 09JUL2021 
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in rat showed that rucaparib caused maternal toxicity and was embryo-toxic. Although no 
rucaparib related effects on sperm total count, density, motility, or morphology were 
identified, based on published studies, PARP inhibitors have the potential to impair 
spermatogenesis and reduce fertility.17-20 
 Summary of Clinical Experience with Rucaparib 
Rucaparib has been evaluated in Phase 1 and 2 clinical studies and is being evaluated in 
ongoing Phase 2 and Phase 3 clinical studies. The early clinical program assessed safety and 
efficacy of rucaparib in patients with malignancies commonly treated with chemotherapeutic 
agents.  
Initially, an intravenous [IV] formulation of rucaparib was administered in combination with 
a variety of chemotherapies; later, the oral formulation of rucaparib was administered in 
combination with chemotherapy and as a monotherapy. The oral formulation as monotherapy 
is the focus of current development efforts. The IV formulation is no longer in use.  
Four studies (A4991002, A4991005, A4991014, CO-338-023 [RUCAPANC]) have been 
completed and 8 studies (CO-338-010, CO-338-014 [ARIEL3], CO-338-017 [ARIEL2], CO-
338-044 [DDI], CO-338-043 [ARIEL4], CO-338-045 [ADME], CO-338-052 [TRITON2], 
and CO-338-063 [TRITON3]) are ongoing.  
Details of all completed, ongoing, and planned studies are described briefly below. 
Additional information is provided in the rucaparib IB.  
Completed Studies  
• A4991002: a Phase 1 open-label, dose-escalation study of IV rucaparib in combination 
with temozolomide (TMZ) in patients with advanced solid tumors (Part 1) or malignant 
melanoma (Part 2).  
• A4991005: a Phase 2, open-label study of IV rucaparib in combination with TMZ in 
patients with metastatic melanoma.  
• A4991014: a Phase 1, open-label, dose-escalation study of IV and oral rucaparib 
administered with different chemotherapeutic agents in patients with an advanced solid 
tumor.  
• CO-338-023 (RUCAPANC): a Phase 2, single-arm, open-label study of monotherapy 
oral rucaparib as treatment for patients with previously treated locally advanced or metastatic 
pancreatic ductal adenocarcinoma and a known deleterious BRCA mutation. 
Ongoing Studies 
• CO-338-010: 3-part, open-label, Phase 1/2 study of monotherapy oral rucaparib. 
o Part 1: a Phase 1 portion evaluating PK and safety of escalating doses of rucaparib in 
patients with solid tumors; this portion identified 600 mg twice daily (BID) as the 
recommended starting dose for future studies (n = 56; completed). 
o Part 2: a Phase 2 portion evaluating the efficacy and safety of rucaparib in patients 
with relapsed, high-grade ovarian cancer associated with a BRCA mutation.  


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 Part 2A enrolled patients with a gBRCA mutation who had received 2 to 4 prior 
treatment regimens (n = 42; enrollment complete).  
 Part 2B enrolled patients with a gBRCA or sBRCA mutation who received at 
least 3 prior chemotherapy regimens (n = 9 as of the 27 June 2016 cut-off date 
[closed to enrollment on 1 July 2016]).  
o Part 3: a Phase 2 portion in patients with a relapsed solid tumor associated with a 
BRCA mutation in order to characterize the PK, food effect, and safety profile of a 
higher dose strength tablet (n = 26; enrollment complete). 
• CO-338-017 (ARIEL2): a 2-part open-label Phase 2 study of monotherapy oral rucaparib 
for treatment of relapsed, high-grade ovarian cancer patients. It is designed to identify tumor 
characteristics that may predict sensitivity to rucaparib. Patients will be classified into 
molecularly-defined subgroups, including tumor BRCA (tBRCA, inclusive of both germline 
and somatic BRCA) and BRCA-like, by a prospectively defined genomic signature.  
o Part 1 enrolled patients with platinum-sensitive, relapsed disease who received ≥ 1 
prior platinum regimen (n = 204; enrollment complete).  
o Part 2 is enrolling patients with relapsed disease who received at least 3 prior 
chemotherapy regimens (n = 262 as of the 27 June 2016 cut-off date [closed to 
enrollment on 29 July 2016]).  
• CO-338-014 (ARIEL3): a Phase 3, randomized, double-blind study of monotherapy oral 
rucaparib versus placebo as switch maintenance treatment in patients with platinum-
sensitive-, relapsed, high-grade ovarian cancer who achieved a response to platinum-based 
chemotherapy (n = 560 as of the 27 June 2016 cut-off date [closed to enrollment on 19 July 
2016]).  
• CO-338-044 (DDI study): a 2-part, Phase 1, open-label, multiple-probe drug-drug 
interaction (DDI) study to determine the effect of rucaparib on PK of caffeine, S-warfarin-, 
omeprazole, midazolam, and digoxin in patients with advanced solid tumors in Part 1, 
followed by optional continued treatment with rucaparib in Part 2 (n = 5; enrollment 
ongoing). 
• CO-338-043 (ARIEL4): a phase 3 study evaluating rucaparib versus chemotherapy as 
treatment for patients with relapsed high-grade ovarian cancer associated with a deleterious 
BRCA1/2 mutation 
• CO-338-045 (ADME): a 2-part open-label Phase 1, single-dose study of the disposition 
of [14C]-radiolabel rucaparib in patients with advanced solid tumors, with the option to 
continue rucaparib therapy. 
• CO-338-052 (TRITON2): a Phase 2 study evaluating rucaparib efficacy in mCRPC 
whose tumors are associated with HRD by enrolling mCRPC patients with mutations in 
BRCA1/2, ATM, or other HR genes. All patients will be required to have progressed on prior 
AR-targeted therapy (abiraterone acetate, enzalutamide, or investigational AR-targeted 
agent) and also have progressed after one prior taxane-based chemotherapy for mCRPC. 
• CO-338-063 (TRITON3): a Phase 3, randomized, 2-arm study evaluating rucaparib vs. 
physician’s choice (abiraterone acetate, enzalutamide or docetaxel) in patients with mCRPC 
associated with a deleterious BRCA1/2 or ATM mutation (n = ~300). 


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 Overview of Clinical Pharmacokinetics  
Assessment of rucaparib PK in cancer patients showed an approximate dose-proportional 
exposure after once daily (QD) or BID dosing, rapid absorption with maximum plasma 
concentration (Cmax) achieved within 1.5 to 6 hours, and distribution into tissue. The oral 
bioavailability was 36% and terminal half-life (T1/2) ranged from 9.23 to 33.6 hours. 
Rucaparib was moderately bound to human plasma proteins in vitro. 
At a dose of 600 mg BID rucaparib, steady-state was achieved after approximately 1 week. 
At the target clinical dose of 600 mg, a high-fat meal increased the Cmax and area under the 
plasma concentration-time curve from 0 to 24 hours (AUC0-24h) of rucaparib by 20% and 
38%, respectively, and delayed the median time to occurrence of Cmax (Tmax) by 
approximately 2.5 hours as compared with these parameters under fasted conditions. The 
effect of food on rucaparib PK is not considered to be clinically significant, thus rucaparib 
can be taken with or without food. 
In a preliminary assessment of rucaparib metabolism in patients, rucaparib biotransformation 
pathways included hydroxylation or oxidation, N-demethylation, deamination, and phase II 
methylation. A carboxylic acid metabolite (M324) and a phase II N-methylated metabolite of 
M324 (M338) were identified as major metabolites.  
Drug interactions with rucaparib as a substrate were assessed in a population PK analysis. 
CYP2D6 phenotypes (poor metabolizers, intermediate metabolizers, normal metabolizers, 
and ultra-rapid metabolizers) and CYP1A2 phenotypes (normal metabolizers and 
hyperinducers) did not significantly impact the steady-state exposure of rucaparib at 600 mg 
BID. Current smokers had overlapping rucaparib exposures as compared to nonsmokers and 
former smokers. Collectively, the results suggest that CYP1A2 and CYP2D6 play a limited 
role in rucaparib metabolism in vivo, and no rucaparib dose adjustment is needed when 
concomitantly administered with CYP inhibitors. 
Concomitant treatment with proton pump inhibitors (PPIs) showed no clinically significant 
effect on rucaparib PK. No dose modification of rucaparib is required for patients who are 
receiving concomitant treatment with a PPI. 
Results from Study CO-338-044 evaluating potential drug-drug interactions (DDI) with 
rucaparib, indicated that rucaparib, at 600 mg BID, moderately inhibited CYP1A2, weakly 
inhibited CYP2C9, CYP2C19, and CYP3A, and showed no clinically significant effect on P-
gp. Caution should be exercised in the concomitant use of drugs that are substrates of the 
above CYP enzymes with narrow therapeutic windows.  
 Overview of Efficacy 
An overview of data are provided below and described in detail in the rucaparib IB.  
Efficacy analysis was based on pooled efficacy data from 106 patients with BRCA mutant 
ovarian cancer, who received two or more prior chemotherapy regimens, and who initiated 
treatment with rucaparib at 600 mg BID in Part 2A of Study CO-338-010 and Parts 1 and 2 
of Study CO-338-017. The enrollment cut-off date was 1 October 2015 (all 42 patients 
enrolled) and the visit data cut-off date was 30 November 2015 for Study CO-338-010 Part 
2A. The enrollment cut-off was a 1 October 2015 and the visit data cut-off was 29 February 
2016 for Part 1 (24 patients) and Part 2 (40 patients) of Study CO-338-017.  


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Efficacy data indicate that many patients with advanced ovarian cancer associated with a 
BRCA1/2 gene mutation and who had two or more prior therapies achieve RECIST and/or 
GCIG cancer antigen 125 (CA125) responses. The confirmed objective response rate (ORR) 
per RECIST by investigator review was 53.8% (57/106) and the confirmed response by 
RECIST or GCIC CA-125 was 70.8% (75/106). The confirmed ORR per RECIST by 
independent review was 41.5% (44/106). In addition, patients without a BRCA1/2 gene 
mutation in tumor tissue are also deriving benefit, with 43% achieving RECIST and/or GCIG 
CA-125 responses. Three mCRPC patients with a BRCA mutation received rucaparib 
monotherapy in Study CO-338-010 or under named patient access, most of whom 
experienced tumor stabilization, decrease of PSA levels, and symptom improvement. 
 Overview of Safety 
Pooled safety data in the treatment setting are provided as of the 01 September 2017 cut-off 
date for the ongoing Studies CO-338-010 (Parts 2A and 2B) and CO-338-017 (ARIEL2; 
Parts 1 and 2), in which 545 patients with relapsed ovarian cancer received 600 mg BID 
rucaparib. Safety data in the maintenance setting are provided as of the 15 April 2017 cut-off 
date for Study CO-338-014 (ARIEL3), in which a total of 561 patients have been treated 
(372 patients in the rucaparib group and 189 patients in the placebo group). Pooled safety 
data from the treatment setting as well as safety data in the maintenance setting are presented 
in Table 3.1 
Patients with ovarian cancer who received 600 mg BID rucaparib in pooled Studies CO-338-
010 (Parts 2A and 2B) and CO-338-017 (Parts 1 and 2) (treatment setting), as well as in 
Study CO-338-014 (maintenance setting), the most common TEAEs reported were primarily 
mild to moderate (Grade 1-2) in severity and include gastrointestinal disorders (nausea, 
vomiting, diarrhea, constipation, and abdominal pain), asthenia/fatigue, decreased appetite, 
and dysgeusia. The most common TEAE ≥ Grade 3 include anemia/decreased hemoglobin, 
ALT/AST increased, neutropenia/decreased ANC, and asthenia/fatigue.  
Effects on cardiac channel activity in vitro and a comprehensive assessment of the effects of 
rucaparib on ECG parameters in cancer patients demonstrated a low risk of cardiac effects by 
rucaparib 
Table 3.1: Incidence of TEAEs (all causality; all grades and ≥ Grade 3) reported in ≥ 
20% of patients - safety population 
Preferred Term 
Treatment Setting Pooled 
Studies CO-338-010 (Parts 
2A and 2B) and CO-338-017 
(ARIEL2 Parts 1 and 2)a 
Maintenance Setting Study CO-338-014 
(ARIEL3)b 
600 mg BID Rucaparib 
(N = 545)  
n (%) 
600 mg BID Rucaparib 
(N = 372) 
n (%) 
Placebo 
(N = 189)  
n (%) 
All 
Grades 
Grade  
≥ 3 
All 
Grades 
Grade  
≥ 3 
All 
Grades 
Grade  
≥ 3 
Nausea 
428 
(78.5%) 
29 
(5.3%) 
280 
(75.3%) 
14 
(3.8%) 
69 
(36.5%) 
1 
(0.5%) 
Asthenia/fatiguec 
409 
(75.0%) 
64 
(11.7%) 
258 
(69.4%) 
25 
(6.7%) 
83 
(43.9%) 
5 
(2.6%) 


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Vomiting 
250 
(45.9%) 
23 
(4.2%) 
136 
(36.6%) 
15 
(4.0%) 
28 
(14.8%) 
2 
(1.1%) 
Anemia/decreased 
hemoglobin 
240 
(44.0%) 
132 
(24.2%) 
139 
37.4%) 
39 
(10.5%) 
11 
(5.8%) 
1 
(0.5%) 
ALT/AST 
increasedc 
214 
(39.3%) 
59 
(10.8%) 
126 
(33.9%) 
39 
(10.5%) 
7 
(3.7%) 
0 
Decreased appetite 
209 
(38.3%) 
16 
(2.9%) 
87 
(23.4%) 
2 
(0.5%) 
26 
(13.8%) 
0 
Constipation 
205 
(37.6%) 
8 
(1.5%) 
136 
(36.6%) 
7 
(1.9%) 
45 
(23.8%) 
2 
(1.1%) 
Dysgeusia 
200 
(36.7%) 
1 
(0.2%) 
146 
(39.2%) 
0 
13 
(6.9%) 
0 
Abdominal pain 
177 
(32.5%) 
22 
(4.0%) 
111 
(29.8%) 
9 
(2.4%) 
49 
(25.9%) 
1 
(0.5%) 
Diarrhea 
176 
(32.3%) 
11 
(2.0%) 
118 
(31.7%) 
2 
(0.5%) 
41 
(21.7%) 
2 
(1.1%) 
Thrombocytopenia/ 
decreased plateletsc 
128 
(23.5%) 
33 
(6.1%) 
104 
(28.0%) 
19 
(5.1%) 
5 
(2.6%) 
0 
Blood creatinine 
increased 
120 
(22.0%) 
3 
(0.6%) 
57 
(15.3%) 
1 
(0.3%) 
3 
(1.6%) 
0 
Dyspnea 
120 
(22.0%) 
5 
(0.9%) 
50 
(13.4%) 
0 
14 
(7.4%) 
0 
Abbreviations: ALT = alanine aminotransferase; AST = aspartate aminotransferase; MedDRA = Medical 
Dictionary for Regulatory Activities; N or n = number of patients; TEAE = treatment-emergent adverse event. 
a. The treatment setting pooled data presented are from the 01 September 2017 cut-off date for the ongoing 
Studies CO-338-010 (Parts 2A and 2B) and CO-338-017 (ARIEL2; Parts 1 and 2). 
b.  Safety data in the maintenance setting are provided as of the 15 April 2017 cut-off date for Study CO-338-
014 (ARIEL3). 
c. Combined MedDRA preferred terms. 
Note: Data are presented by decreasing frequency for TEAEs of all grades for the treatment setting pooled data. 
The laboratory abnormalities reported in Study CO-338-014 (ARIEL3) were consistent with 
the TEAEs, with decreased hemoglobin, increased ALT, increased AST, and increased serum 
creatinine, most common in patients in the rucaparib group. Decreased platelets, neutrophils, 
leukocytes, lymphocytes, increased alkaline phosphatase and increased cholesterol were 
observed to a lesser extent. 
ALT/AST elevations occurred early in treatment (i.e., by Day 1 of Cycle 2) and then resolved 
or stabilized over time. Treatment with rucaparib was continued at either the initial 600 mg 
BID dose or a lower dose. Elevations in ALT/AST were rarely accompanied by a 
concomitant elevation in bilirubin.., and there have been no cases of Hy’s Law attributed to 
the use of rucaparib. Continued dosing with rucaparib in the presence of Grade 3 ALT/AST 
elevations is permitted if there are no other signs of liver toxicity. 
Creatinine elevations were also observed early in treatment (i.e., by Day 1 of Cycle 2) and 
then stabilized with continued rucaparib treatment. 
 Adverse Events of Special Interest  
A review of all reports of MDS and AML that have occurred in the entire clinical 
development program up to 10 April 2017 revealed a total of 10 reports in patients exposed 
to rucaparib in Studies CO-338-010, CO-338-017, and CO-338-014.  


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The rate of MDS/AML was 0.5% for patients on treatment and during the 28 day safety 
follow-up, and 0.9% for all patients including during the long-term safety follow-up (rate is 
calculated based on overall safety population of 1077 patients exposed to at least one dose of 
oral rucaparib in all clinical studies). 
There was one case of AML in 189 patients exposed to placebo in Study CO-338-014. 
All of the patients diagnosed with MDS or AML had received multiple cycles and regimens 
of prior chemotherapy, including platinum- and/or taxane-containing regimens. One patient 
had also received prior treatment with an alkylating agent (cyclophosphamide) and 2 patients 
had received radiation for breast cancer (1 patient received rucaparib and 1 received 
placebo). One patient was discontinued from rucaparib 14 months prior to MDS diagnosis 
and was treated with olaparib for 13 months between rucaparib discontinuation and MDS 
diagnosis. One patient discontinued rucaparib 9 months prior to MDS diagnosis and was 
treated with cisplatin and trabectedin for an unspecified time between rucaparib 
discontinuation and MDS diagnosis. Exposure to DNA-damaging therapies for ovarian and 
breast cancer present an increased risk of developing MDS or AML 
In patients diagnosed with MDS, duration from start of primary disease treatment to 
diagnosis was between approximately 1 and 23 months (i.e., 35 days to approximately 693 
days). In patients diagnosed with AML, duration from start of primary disease treatment to 
AML diagnosis was between approximately 3.5 and 28.5 months (i.e., 106 to 868 days). In 
the patient with MDS that evolved into AML, the duration of time from starting treatment 
with rucaparib to diagnosis of MDS was approximately 12.5 months (i.e., 380 days) and from 
start of rucaparib to diagnosis of AML was approximately 18 months (i.e., 541 days). 
Nearly every patient who developed MDS/AML reported having experienced 
multiple/persistent cytopenias prior to the diagnosis of MDS/AML. The cytogenetic 
abnormalities currently available in 3 of the 4 patients diagnosed with AML were consistent 
with aberrations (primarily abnormalities in chromosome 5) typically observed in patients 
with secondary MDS/AML due to prior chemotherapy. One patient who developed both 
MDS and AML had chromosomal abnormality in chromosome 7.35. The patients who have 
developed MDS and AML have significant confounding risk factors, including prior 
cytotoxic chemotherapy, as well as a deleterious BRCA mutation presenting a higher risk of 
developing one or more malignancy (ies). 
Based upon the above confounding factors, there is insufficient scientific evidence to 
conclude that MDS and AML are causally related to rucaparib. 
4 STUDY DESIGN 
4.1 
Description 
This is a single arm, open label, phase II trial to assess efficacy of rucaparib. 
4.2 
Number of Patients 
15 evaluable subjects will be enrolled.  


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4.3 
Number of Study Centers 
This study will be conducted at Huntsman Cancer. 
4.4 
Study Duration  
Expected enrollment duration is 12 months, patients will remain on study treatment until 
PSA progression defined by PCWG3 (unless they meet the criteria for continued treatment 
outlined in section 6.4.1), with 2 years of follow up after study treatment. We anticipate a 
total of 2-3 years until completion of the clinical trial. 
 


S h ort Title: R uc a p ari b N o n met ast atic  pr Ost Ate wit h B R C A ness ( R O A R)
Versi o n D ate: 0 9J U L 2 0 2 1
Pa ge 2 1 of 5 2
5 
E LI GI BI LI T Y C RI T E RI A
T his eli gi bilit y c hec klist is use d t o deter m i ne patie nt eli gi bilit y a n d file d wit h e nr olli n g 
i n vesti gat or’s si g nat ure i n t he patie nt researc h c hart. 
P atie nt N o. _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
P atie nt’s I niti a ls: ( L, F, M) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ 
5. 1 
I ncl usi o n Criteri a
Yes/ N o ( Res p o nse of “ n o ” = p atie nt i neli gi ble)
_ _ _ _ _ H or m o ne-se nsiti ve, hist ol o gi call y pr o ve n a de n ocarci n o ma of t he pr ostate wit h 
B R C A ness ( defi ne d as a n alterati o n i n o ne or m ore of t he f oll o wi n g ge nes B A R D 1, 
B R C A 1, B R C A 2, B RI P 1, C H E K 1, C H E K 2, F A N C A, N B N,  P A L B 2, R A D 5 1 C, 
R A D 5 1 D,  R A D 5 1, R A D 5 1 B) fr o m s oft-tiss ue base d ge n o mic testi n g or li q ui d 
bi o ps y base d ge n o mic or ge netic testi n g. Pat h o ge nic or li kel y pa t h o ge nic alterati o ns 
are acce pte d.
_ _ _ _ _ E C O G/ Z u br o d sc ore of 0- 2. 
_ _ _ _ _ At a mi ni m u m, s u bjects m ust ha ve re cei ve d defi niti ve l ocal t hera p y  wit h 
c urati ve i nte nt (i.e., pr ostate ct o m y a n d/ or ra diati o n t hera p y)  wit h or wit h o ut s yste mic 
t hera p y .  
_ _ _ _ _ Test oster o ne le vel is > 5 0 n g/ d L.
_ _ _ _ _ Be at least 1 8 years ol d at t he ti me t he i nf or me d c o nse nt f or m is si g ne d. 
_ _ _ _ _ De m o nstrate a de q uate or ga n f u ncti o n as defi ne d i n t he ta ble bel o w, all 
scree ni n g la bs s h o ul d be perf or me d wit hi n 2 8 da ys of treat me nt i nitiati o n.
He m at ol o gic:
o
A bs ol ute ne utr o p hil c o u nt 
.
o
.
o
.
He p atic: 
o
2 
Gil bert’s s y n dr o me.  
o
U L N
Re n al: 
o
Creati ni ne 
o
Creati ni ne cleara nce > 4 0 m L/ mi n f or s u bject wit h creati ni ne le vels > 
. 
o
N ote: G F R m ay als o be use d i n  pl ace of cre ati ni ne or Cr Cl
C o a g ul ati o n: 
o


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o If on active anticoagulants prior to study treatment, levels must be 
within standard therapeutic ranges per investigator 
 _____ Highly effective barrier methods must be used with all sexual activity and 
contraception methods must be practiced for all subjects throughout the study and for 
at least 6 months after last rucaparib treatment administration if the risk of conception 
exists (section 7.2). 
 _____ Recovery to baseline or Grade ≤ 1 CTCAE v5.0 from toxicities related to any 
prior treatments within the context of their definitive local therapy for their prostate 
cancer, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy. 
 _____ Subject is able to provide informed consent and willing to sign an approved 
consent form that conforms to federal and institutional guidelines. 
 
5.1.10 _____ Subject must have confirmed PSA progression based on at least two time 
points taken at least one week apart to confirm rising trend.  
5.2 
Exclusion Criteria 
Yes/No (Response of “yes” = patient ineligible) 
 _____ Subjects with metastases defined by conventional scans (CT, MRI, NM Bone 
Scan). Disease identified on molecular imaging (e.g., fluciclovine-PET) is not 
exclusionary. 
 _____ Arterial or venous thrombi (including cerebrovascular accident), myocardial 
infarction, admission for unstable angina, cardiac angioplasty, or stenting within the 
last 90 days prior to screening. 
 _____ Pre-existing duodenal stent, recent (within ≤ 3 months) or existing bowel 
obstruction, and/or any gastrointestinal disorder or defect that would, in the opinion 
of the Investigator, interfere with absorption of rucaparib. 
 _____ Inability to swallow tablets. 
 _____ Evidence or history of clinically significant bleeding disorder per the 
determination of the treating investigator. 
 _____ Prior systemic therapy within the past 30 days prior to Day 1 (or 5 half-lives of 
the drug, whichever is shorter). 
 _____ Diagnosis of another malignancy within 2 years before first dose of study 
treatment only if the cancer will either interfere with patient safety or interfere with 
the primary endpoint, per the judgement of the Principal Investigator. Patients who 
have been diagnosed with superficial skin cancers, or localized, low grade tumors 
deemed cured or with a prolonged natural history (e.g., estimated overall survival > 5 
years), may be included. 
 _____ Prior treatment with any PARP inhibitor, mitoxantrone, cyclophosphamide, or 
any platinum based chemotherapy.  


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 _____ Clinically significant (i.e., active) cardiovascular disease at the time of 
enrollment: congestive heart failure (> New York Heart Association Classification 
Class II), or serious cardiac arrhythmia requiring medication. 
 _____ Other severe acute or chronic medical conditions including cardiovascular, 
endocrine, neurologic, pulmonary or psychiatric conditions including recent (within 
the past year) or active suicidal ideation or behavior; or laboratory abnormalities that 
may increase the risk associated with study participation or study treatment 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the patient inappropriate for entry into this 
study. 
 _____Major surgery (e.g., GI surgery, removal or biopsy of brain metastasis) within 8 
weeks before first dose of study treatment. Complete wound healing from major 
surgery must have occurred 1 month before first dose and from minor surgery (e.g., 
simple excision, tooth extraction) at least 28 days before first dose. Subjects with 
clinically relevant ongoing complications from prior surgery are not eligible. 
 
I certify that this patient meets all inclusion and exclusion criteria for enrollment onto 
this study.  
______________________________ 
 
_________ 
_______ 
Investigator Signature   
 
 
Date  
Time 
 
 


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6 TREATMENT PLAN 
6.1 
Administration Schedule 
Treatment with rucaparib will begin on Cycle 1 Day 1 and continue daily at 600 mg PO BID. 
Therapy continues according to criteria in Section 6.4. 
All trial treatments will be administered on an outpatient basis. 
6.2 
Rucaparib Treatment  
 How Supplied, Stored, Packaged and Labeled 
All tablets are provided in high-density polyethylene (HDPE) bottles with child-resistant 
caps and should be stored in the provided containers between 15 °C and 30 °C (59 °F and 86 
°F). Patients will be dispensed one or more strengths depending on their current dose of 
rucaparib. The number of bottles of each strength dispensed will be sufficient to supply 30 
days treatment per cycle. 
Study drug containers with rucaparib tablets will be labeled according to national regulations 
for investigational products by the drug manufacturer. 
Rucaparib camsylate (formerly known as PF-01367338 and AG-014447) is an oral 
formulation with a molecular weight of 555.67 Daltons. Rucaparib tablets for oral 
administration will be supplied by Clovis. A brief description of the investigational product is 
provided below: 
Drug Name 
Rucaparib 
INN 
Rucaparib 
Formulation 
Tablet; film coated; 200 mg, 250 mg, 300 mg 
How Supplied 
200, 250, and/or 300 mg strength (based on free base) in high-density 
polyethylene bottles or equivalent with child-resistant caps. Patients 
may receive 1 or more strengths. Each bottle contains 60 tablets 
Storage Conditions 15–30 °C (59–86 °F)  
 Preparation and Administration 
Daily oral rucaparib at 600 mg BID with 8 oz (240 mL) of room temperature water, taken on 
an empty stomach or with food. Tablets should be swallowed whole without crushing or 
chewing.  
 Accountability and Compliance 
Rucaparib tablets will be dispensed to the patient in sufficient quantity to last until Day 1 of 
the next treatment cycle. Patients will keep all unused tablets and containers (empty, partially 
used, and/or unopened) for accountability at the next visit.  
Patients should take rucaparib doses as close to 12 hours apart as possible, preferably at the 
same times every day. If a patient misses a dose (i.e., does not take it within 4 hours of the 
scheduled time), the patient should skip the missed dose and resume taking rucaparib with 
the next scheduled dose. Missed or vomited doses should not be made up. 


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Patients will be instructed to record daily doses taken or not taken in a patient diary. 
Treatment with rucaparib is continuous and each cycle will comprise 28 days. 
All study drugs will be stored at the Huntsman Cancer Institute Investigational Pharmacy in 
accordance with Good Clinical Practice (GCP) and GMP requirements and the instructions 
given by the clinical supplies department of the sponsor, and will be inaccessible to 
unauthorized personnel. The investigator, or a responsible party designated by the 
investigator, must maintain a careful record of the inventory and disposition of the agent. 
An adequate record of receipt, distribution, and return of all study drugs must be kept in the 
form of a Drug Accountability Form. Subject compliance with the treatment and protocol 
includes willingness to comply with all aspects of the protocol, and to have blood collected 
for all safety evaluations. At the discretion of the principal investigator, a subject may be 
discontinued from the trial for non-compliance with follow-up visits or study drug.  
Instructions on medication resupply and destruction will be made available to affected parties 
as applicable.  
At the conclusion of the study, and, as appropriate during the course of the study, the 
Investigator will return all used and unused study drug, packaging, drug labels, and a copy of 
the completed drug accountability ledger to Clovis.  
6.3 
Concomitant Medications 
 Hematopoietic Growth Factors and Blood Products 
Erythropoietin, darbepoetin alfa, and/or hematopoietic colony-stimulating factors for 
treatment of cytopenias should be administered according to institutional guidelines. 
Transfusion thresholds for blood product support will be in accordance with institutional 
guidelines. 
 CYP450 Isoenzyme Inhibitors, Inducers, and Substrates 
Based on the results from the in vivo CYP interaction study (CO-338-044), rucaparib is a 
moderate inhibitor of CYP1A2, and a weak inhibitor of CYP2C9, CYP2C19, and CYP3A. 
Caution should be used in patients on rucaparib taking concomitant medicines that are 
substrates of CYP1A2, CYP2C9, CYP2C19, and/or CYP3A with narrow therapeutic 
windows. Examples of such drugs are provided in table 6.1. 
Although in vitro rucaparib metabolism mediated by CYP3A4 was slow, a significant 
contribution of CYP3A4 in vivo cannot be excluded. Caution should be used for concomitant 
use of strong CYP3A4 inhibitors or inducers. Selection of an alternative concomitant 
medication is recommended. 
Table 6.1: Examples of CYP substrates with narrow therapeutic range 
CYP Enzyme 
Substrates with Narrow Therapeutic Rangea 
CYP1A2 
Tizanidine, theophylline 
CYP2C9 
Warfarin, phenytoin  
CYP2C19 
S-mephenytoin  


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CYP3A 
Alfentanil, astemizole, cisapride, cyclosporine, dihydroergotamine, 
ergotamine, fentanyl, pimozide, quinidine, sirolimus, tacrolimus, 
terfenadine 
The table is based on the Draft FDA Guidance on Drug Interaction Studies — Study Design, Data Analysis, 
Implications for Dosing, and Labeling Recommendations, 2012  
a CYP substrates with narrow therapeutic range refers to drugs whose exposure-response relationship indicates 
that small increases in their exposure levels by the concomitant use of CYP inhibitors may lead to serious safety 
concerns (e.g., Torsades de Pointes). 
 Anticoagulants 
Caution should be exercised in patients receiving rucaparib and concomitant warfarin 
(Coumadin) as rucaparib showed a mixed inhibition of CYP2C9 in vitro. If appropriate, low 
molecular weight heparin should be considered as an alternative treatment. Patients taking 
warfarin should have international normalized ratio (INR) monitored regularly per standard 
clinical practice. 
 Other Concomitant Medications 
Therapies considered necessary for the patient’s well-being may be given at the discretion of 
the investigator and should be documented on the eCRF. Other concomitant medications, 
except for analgesics, chronic treatments for concomitant medical conditions, or agents 
required for life-threatening medical problems, should be avoided. Herbal and 
complementary therapies should not be encouraged because of unknown side effects and 
potential drug interactions, but any taken by the patient should be documented appropriately 
on the eCRF.  
Rucaparib marginally increased digoxin area under the plasma concentration-time curve 
(AUC) by 20%. Caution should be exercised for patients receiving rucaparib and requiring 
concomitant medication with digoxin. Patients taking digoxin should have their digoxin 
levels monitored after starting rucaparib and then regularly per standard clinical practice.  
In vitro, rucaparib is a potent inhibitor of MATE1 and MATE2-K, a moderate inhibitor of 
OCT1, and a weak inhibitor of OCT2. As inhibition of these transporters could increase 
metformin renal elimination and decrease liver uptake of metformin, caution is advised when 
metformin is co-administered with rucaparib. In addition, rucaparib is an inhibitor of the 
BCRP with 50% inhibitory concentration (IC50) value suggesting potential BCRP inhibition 
and increased exposures of medicinal products that are BCRP substrate (e.g., rosuvastatin). 
 Photosensitivity 
Patients should use typical precautions when going outside, such as applying sunscreen 
and/or covering exposed skin with clothing and wearing a hat and sunglasses, as 
photosensitivity has been observed. 
6.4 
Duration of Therapy 
 


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 Treatment after PSA Progression 
If PSA progression per PCWG3 is demonstrated, patients may continue on study 
therapy if it is felt by the treating physician to be of clinical benefit to the patient.  
Study therapy may be continued after PSA progression at the discretion of the treating 
physician. However, the following criteria must be met: 
• No decline in ECOG performance status;  
• Absence of clinical signs and symptoms (including worsening of laboratory values) 
of disease progression; 
• Absence of rapid progression of disease; 
• PSA ≤100% increase or absolute increase of 5 ng/mL from baseline value, 
whichever is greater.  
• Absence of progressive tumor at critical anatomical sites (i.e. cord compression) 
requiring urgent alternative medical intervention.  
Before continuation of treatment after initial PD, the patient must be re-consented via 
informed consent addendum and informed that, by continuing to receive investigational 
products, the patient may be foregoing approved or investigational therapies with 
possible clinical benefit(s). Patients should continue to follow all assessments as 
outlined in the Study Calendar. 
 
Once PSA progression has been documented, disease assessments should continue per 
the Study Calendar to ensure the above criteria is consistently met.  
 Criteria for discontinuation of treatment (“off-treatment”) 
Patients may withdraw from treatment or the study overall at any time at their own request, 
or they may be withdrawn at the discretion of the Investigator or Sponsor for safety, 
behavioral reasons, or the inability of the patient to comply with the protocol-required 
schedule of study visits or procedures. In addition to the drug-specific discontinuation 
criteria listed in Dose Modification Section and the Dose Limiting Toxicity Section, the 
following will result in treatment discontinuation: 
• Unacceptable Toxicity 
• Subject withdraws consent from the study treatment and/or study procedures.   
• Demonstration of continued non-compliance with protocol requirements as 
determined by the principle investigator 
• Significant protocol violation as determined by the principal investigator 
• The patient refused further treatment 
• Study terminated  
• Lost to follow-up 
• Death 


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• The patient does not meet the criteria for continued treatment post-progression as 
outlined in section 6.4.1. 
 Criteria for discontinuation of study (“off study”) 
Subjects will be taken off study for the following: 
• Screen failure. 
• If, in the investigator's opinion, the continuation of the trial would be harmful to the 
subject's well-being. 
• Development of intercurrent illness or situation which would, in the judgment of the 
investigator, significantly affect assessments of clinical status and trial endpoints. 
• Participant requests to be withdrawn from the study. 
• Subject is lost to follow-up. 
• The patient completed the study follow-up period. 
• Death. 
• Deterioration of ECOG performance status to 4 
7 TOXICITIES AND DOSAGE MODIFICATION 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) 
Version 5.0 for adverse event and serious adverse event reporting.  
7.1 
Dose Modifications 
The most common effects of rucaparib treatment include gastrointestinal disorders (nausea, 
vomiting, diarrhea, and constipation), asthenia/fatigue, clinical chemistry elevations 
(ALT/AST, creatinine, and cholesterol), myelosuppression (decreases in hemoglobin, 
lymphocytes, platelets, and neutrophils), dysgeusia, and decreased appetite. Modification of 
rucaparib dose may be a necessary component of AE management, and study specific 
protocol guidelines for dose modifications should be followed. Dose interruptions, with or 
without subsequent dose reductions, may help to ameliorate AEs attributed to rucaparib 
therapy. 
Treatment with rucaparib should be held if any of the following are observed and a dose 
reduction should be considered or implemented.  
• Grade 3 or 4 hematologic toxicity 
• Grade 3 or 4 non-hematologic toxicity (except for alopecia, nausea, vomiting, or 
diarrhea adequately controlled with systemic antiemetic/antidiarrheal medication 
administered in standard doses according to the study center routines). Grade 3 or 
Grade 4 ALT/AST elevations should be managed as described below.  
• In addition, and at the discretion of the investigator, the dose of rucaparib may be 
held and/or reduced for Grade 2 toxicity not adequately controlled by concomitant 
medications and/or supportive care. 


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 Management of anemia including evaluation for MDS/AML and follow-up of 
patients who discontinue treatment with ongoing anemia 
• If the patient develops anemia CTCAE Grade ≥ 3, rucaparib treatment should be held 
until the anemia improves to CTCAE Grade ≤ 2 whereupon daily dosing may then be 
resumed at either the same dose or a lower dose, per investigator discretion. 
• If the duration of dosing is interrupted for > 14 consecutive days due to anemia 
CTCAE Grade ≥ 3, treatment should be permanently discontinued, unless otherwise 
agreed between the investigator and Clovis. 
• In addition, if anemia CTCAE Grade ≥ 3 persists for > 14 consecutive days, or a 
dependence upon blood transfusion occurs, then weekly complete blood counts 
should be performed until resolution of the event.  
• If, after 42 days of interruption of rucaparib, the anemia has not improved to CTCAE 
Grade ≤ 1 then the patient should be referred to a hematologist and analysis of the 
bone marrow with cytogenetic studies are recommended according to standard 
hematologic practice. 
• The bone marrow analysis should include a bone marrow aspirate (for cellular 
morphology, cytogenetic analysis, and flow cytometry) and a core biopsy (for bone 
marrow cellularity). 
 Management of rucaparib treatment-emergent ALT/AST Elevations  
Grade 3 ALT/AST elevations have been successfully treated with treatment interruption 
and/or a reduction in dose. The data reported as of the data cut-off date suggest that many 
patients have been able to continue treatment with 600 mg BID following a dose interruption, 
without any further elevation or recurrence of Grade 3 ALT/AST. The following guidelines 
have been suggested for managing Grade 3/4 ALT/AST elevations. 
• Grade 4 ALT/AST elevations: hold rucaparib until values have returned to Grade 2 or 
better, then resume rucaparib with a dose reduction. Monitor liver function tests 
weekly for 3 weeks after rucaparib has been restarted. 
• Grade 3 ALT/AST elevations, in the absence of other signs of liver dysfunction, 
should be managed as follows: 
o Monitor liver function tests weekly until improvement to ≤ Grade 2. 
o Continuation of rucaparib with elevation of ALT/AST up to Grade 3 is permitted 
provided bilirubin is < ULN and alkaline phosphatase is < 3 x ULN. 
o If patient has Grade 3 ALT/AST and continues on rucaparib, and levels do not 
decline within 2 weeks or they continue to rise, treatment interruption and 
improvement to ≤ Grade 2 will be required before rucaparib can be resumed, 
either at the current dose or at a reduced dose. 
 Management of rucaparib treatment-emergent cholesterol elevations 
Grade 3 cholesterol elevations have been successfully managed with dose interruption and/or 
dose reduction and concomitant treatment with a HMG-CoA reductase inhibitor (commonly 
known as statin). Study drug must be held for Grade 3-4 elevated cholesterol but can be 
resumed after improvement to Grade 2 or less. Supportive care treatment will be based on 


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approved risk categories for patients found to have elevated levels. Treatment will be 
determined by the patients primary care physician or cardiologist based on current CHEST 
guidelines. Caution should be noted for the use of certain statin drugs, see section 6.3. 
 Management of rucaparib treatment-emergent myelosuppression 
Grade 3/4 myelosuppressive events have been successfully treated with supportive care and 
dose interruption/reduction. Additional diagnostic evaluation, including bone marrow 
examination, should be considered for patients with persistent myelosuppression that does 
not stabilize or recover with rucaparib treatment modification. 
Dose reduction steps are presented in Table 7.1. 
Dose re-escalation upon improvement of toxicity to CTCAE Grade ≤ 1 is permitted at the 
discretion of the investigator.  
Table 7.1. Rucaparib Dose Reduction Steps 
Starting Dose 
600 mg BID 
Dose Level 1 
500 mg BID 
Dose Level 2 
400 mg BID 
Dose Level 3* 
300 mg BID 
* Consult with Principal Investigator and Medical Monitor before reducing to dose level 3. Further dose 
reduction may be possible, but require consultation with the investigator-sponsor. 
 Rucaparib Re-treatment Criteria 
Following a dose interruption, treatment may resume if:  
• ANC ≥ 1.0 × 109/L  
• Platelet count ≥ 100 × 109/L 
• Non-hematologic toxicities have returned to baseline or  CTCAE Grade ≤ 1 severity 
(or, at the investigator’s discretion, CTCAE Grade ≤ 2 severity if not considered a 
safety risk for the patient). Grade 3 or Grade 4 ALT/AST elevations should be 
managed as described above. 
7.2 
Contraception 
It is not known if rucaparib has transient adverse effects on the composition of sperm. The 
investigational product may be transferred to a partner through semen and condoms must be 
used with all sexual activity.  
For this trial, subjects will be considered to be of non-reproductive potential if they have 
azoospermia (whether due to having had a vasectomy or due to an underlying medical 
condition). Subjects of non-reproductive potential must agree to use condoms with all sexual 
activity. 
Subjects of reproductive potential must agree to avoid impregnating a partner or donating 
sperm while receiving study drug and for 6 months after the last dose of study drug by 
complying with the following: 
(1) Males must agree to use condoms with all sexual activity. 


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AND  
(2) Use (or have their partner use) highly effective contraception during heterosexual 
activity, if their partner is of reproductive potential.  
Highly effective methods of contraception are‡: 
• Intrauterine device (IUD) 
• Vasectomy  
• Contraceptive rod implanted into the skin 
• Tubal ligation of female partner 
• Hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or progestin-
only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous 
contraceptive injection 
Of note: spermicides, diaphragm, sponge, and caps are NOT acceptable as they are not 
included in the highly effective methods. 
‡ If a contraceptive method listed above is restricted by local regulations/guidelines, then it 
does not qualify as a highly effective method of contraception for subjects participating at 
sites in this country/region. 
Subjects should be informed that taking the study medication may involve unknown risks to 
the fetus (unborn baby) if pregnancy were to occur during the study. In order to participate in 
the study subjects of childbearing potential must adhere to the contraception requirement 
(described above) from the day of study medication initiation (or 14 days prior to the 
initiation of study medication for oral contraception) throughout the study period up to 6 
months after the last dose of trial therapy. If there is any question that a subject of 
childbearing potential will not reliably comply with the requirements for contraception, that 
subject should not be entered into the study. 
7.3 
Supportive Care 
All supportive measures consistent with optimal patient care will be given throughout the 
study.


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8 STUDY CALENDAR 
1 cycle = 28 days (± 3 days) 
Examination 
Screening1 
C1D12 
C(2+)D13 
PSA Progression 
Confirmation20 
End of 
Treatment18  
Follow-
up16 
Informed consent 
X 
 
 
 
 
 
Treatment after PSA 
Progression ICF20 
 
 
 
X 
 
 
Medical history 
X 
 
 
 
 
 
Eligibility criteria4 
X 
 
 
 
 
 
Vital signs 
X 
X 
X 
X 
X 
 
Physical examination 
X 
X 
X 
X 
X 
  
ECOG performance 
status 
X 
X 
X 
X 
X 
 
Hematology5 
X 
X 
X 
X 
X 
  
Chemistry6 
X 
X 
X 
X 
X 
  
Lipid Panel7 
X 
X 
X 
X 
X 
 
PSA8 
X 
X 
X 
X 
X 
X8 
Urinalysis 
X 
 
 
 
 
 
Coagulation Panel17 
X 
 
 
 
 
 
Testosterone 
X19 
 
 
 
 
 
ECG  
X 
 
 
 
 
 
Adverse Event 
Assessment 
 
X 
X 
X 
X 
 
Concomitant Medication 
Review 
X 
X 
X 
X 
X 
 
CT scans (c,a,p) 
X 
 
 
X15 
 
 
NM Bone Scans 
X 
 
 
X15 
 
 


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Examination 
Screening1 
C1D12 
C(2+)D13 
PSA Progression 
Confirmation20 
End of 
Treatment18  
Follow-
up16 
Rucaparib 
administration9 
 
X 
X 
 
 
 
Blood for Correlative 
Studies10 
X 
 
X10 
X10 
X10 
 
Urine for Correlative 
Studies11 
X 
 
X11 
X11 
X11 
 
Archival Tissue for 
Correlative Studies12 
X 
 
 
 
 
 
BRCAness Test13 
X 
 
 
 
 
 
Optional biopsy14 
 
 
 
X 
 
 
Survival Follow-up 
 
 
 
 
 
X 
 
1. 
All Pre-study/Screening procedures should be completed within 4 weeks of study enrollment. CT Scan and NM Bone scan do not need to be 
repeated if done within preceding 90 days of visit. 
2. 
C1D1 procedures do not need to be repeated if screening procedures have been done within 7 days of start of treatment. 
3. 
Cycles will continue at 28 ± 3 days according to criteria in Section 6.4. 
4. 
Confirmation of BRCAness by previous result or prospective analysis of archival tissue or blood sample biopsy. If archival tissue is 
unavailable, a new biopsy will NOT be required. 
5. 
Hematology includes CBC with differential and platelets. 
6. 
Chemistry includes Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, Total Bilirubin, Calcium, 
Carbon Dioxide, Creatinine, Chloride, Glucose, Potassium, Protein, Sodium, and Urea Nitrogen. 
7. 
Lipid panel to consist of cholesterol, triglycerides, LDL cholesterol HDL Cholesterol, VLDL, and non-HDL Cholesterol. 
8. 
If treatment is discontinued prior to PSA progression, PSA testing will continue throughout follow-up until PSA progression or start of 
another treatment. Patients who have PSA progression prior to discontinuing treatment do not need to have PSA testing performed during 
follow-up.  
9. 
Rucaparib will be administered as described in Section 6. 
10. 
Blood collection for biomarkers will be collected at screening, C3D1, C7D1, and confirmed PSA disease progression (± 7 days), if 
applicable, or at EOT visit (whichever occurs first).  


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11. 
For patients enrolled with an intact prostate, urine collection for biomarkers will be collected at screening,C3D1, C7D1, and confirmed PSA 
disease progression (± 7 days), if applicable, or at EOT visit (whichever occurs first). 
12. 
Archival tissue will be collected at screening (if available). Archival tissue should not be cut until instructed by the central lab. 
13. 
Genomic or genetic testing for ‘BRCAness’ will be confirmed with either blood or tissue based testing.  
14. 
An optional fresh tissue biopsy may be obtained at PSA Progression Confirmation Visit (± 28 days) for subjects with radiographic disease 
progression.  
15. 
CT scans of the chest/abdomen and pelvis and NM bone scans will be done at the time of PSA Progression Confirmation Visit (± 28 days) 
as defined in section 10.1. 
16. 
Follow-up should occur every 90 days (± 14 days) for 2 years following End of Treatment as per standard of care (section 9). 
17. 
Coagulation Panel includes PT/INR, PTT. 
18. 
The end of treatment visit should occur within +/-3 days of the decision to discontinue treatment. If this visit overlaps with a regularly 
scheduled visit, only the procedures listed in the calendar for the EOT visit will be performed.  
19. 
To be performed only if the subject has completed hormone therapy. Screening testosterone may be performed within 84 days of study 
enrollment. 
20. 
Only patients who have suspected PSA progression during a regular study visit will have testing to confirm PSA progression at their next 
regularly scheduled visit. Before continuation of treatment after confirmed PSA progression, the patient must agree to sign the 
Treatment After Progression Informed Consent Form. Patients may complete the assessments required for PSA progression in 
conjunction with the next regularly scheduled cycle visit or at EOT.


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9 STUDY PROCEDURES 
9.1 
Screening 
• Informed Consent 
• Physical exam (including weight and vital signs) 
• Review of medical history/baseline symptoms 
• Confirmation of BRCAness by previous result or prospective analysis of archival tissue 
or blood sample biopsy. If archival tissue is unavailable, a new biopsy will NOT be 
required 
• 12-lead ECG (if medically indicated) 
• ECOG Performance status 
• Laboratory assessments: 
o Complete Blood Count (CBC) with differential (w/diff) 
o Complete Metabolic Panel (CMP) to include Albumin, Alkaline Phosphatase, 
Aspartate Aminotransferase, Alanine Aminotransferase, Total Bilirubin, Calcium, 
Carbon Dioxide, Creatinine, Chloride, Glucose, Potassium, Protein, Sodium, and 
Urea Nitrogen (fasting is not required) 
o Coagulation to include PT, PTT, INR 
o Lipid Panel to include cholesterol, triglycerides, LDL cholesterol HDL Cholesterol, 
VLDL and non-HDL Cholesterol (fasting not required) 
o PSA 
o Testosterone (for subjects who have previously been treated with hormone therapy) 
• Blood collection for correlative studies (see Section 14.1.1 for details) 
• Urine collection for correlative studies. Prior to collection of the urine specimen, a 
prostate exam will be performed by the treating physician (see Section 14.1.2 for details)  
• Archival tissue collection for correlative studies (see Section 14.1.3 for details) 
9.2 
On-Treatment Evaluations (Day 1 of each cycle) 
• Physical Exam (including weight and vital signs) 
• ECOG Performance Status 
• Laboratory assessments (do not need to be repeated at C1D1 if screening labs were 
performed within 7 days prior to treatment initiation): 
o CBC w/diff 
o CMP as defined in Section 9.1 
o Lipid Panel as defined in Section 9.1 
o PSA 
• Blood collection for biomarkers at C3D1 and C7D1 (see Section 14.1.1 for details) 
• Urine collection for biomarkers at C3D1 and C7D1. Prior to collection of the urine 
specimen, a prostate exam will be performed by the treating physician (see Section 14.1.2 
for details). 


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• Safety assessment: monitoring and recording all adverse events and serious adverse 
events using the CTCAE version 5.0 
• Review of concomitant medications 
• Study drug administration & patient resupply (enough to last until Day 1 of the next 
treatment cycle). 
9.3 
PSA Progression Confirmation Visit  
Only for patients who have suspected PSA Progression at one of their regularly scheduled visits. 
Before continuation of treatment after confirmed PSA progression, the patient must agree to sign 
the Treatment After Progression Informed Consent Form. Patients may complete the assessments 
required for PSA progression in conjunction with the next regularly scheduled cycle visit or EOT 
Informed consent to treatment beyond PSA Progression  
• Physical Exam (including weight and vital signs) 
• ECOG Performance Status 
• Laboratory assessments  
o CBC w/diff 
o CMP as defined in Section 9.1 
o Lipid Panel as defined in Section 9.1 
o PSA 
• Blood collection for biomarkers (± 28 days) (see Section 14.1.1 for details) 
• Urine collection for biomarkers ± 28 days). . Prior to collection of the urine specimen, a 
prostate exam will be performed by the treating physician (see Section 14.1.2 for details). 
• Safety assessment: monitoring and recording all adverse events and serious adverse 
events using the CTCAE version 5.0 
• Review of concomitant medications 
• CT scans of the chest abdomen and pelvis (± 28 days) 
• Nuclear Medicine (NM) Bone Scan (± 28 days) 
• Optional biopsy (± 28 days) only for subjects who demonstrate radiographic progression. 
See Section 14.1.3 for details 
9.4 
End of Treatment  
• Physical Exam (including weight and vital signs) 
• ECOG Performance Status 
• Laboratory assessments: 
o CBC w/diff 
o CMP as defined in Section 9.1 
o Lipid Panel as defined in Section 9.1 
o PSA 
• Blood collection for biomarkers (± 28 days) (see Section 14.1.1 for details). (At 
confirmed PSA progression or EOT, whichever comes first). 


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• Urine collection for biomarkers ± 28 days). Prior to collection of the urine specimen, a 
prostate exam will be performed by the treating physician (see Section 14.1.2 for details). 
(At confirmed PSA progression or EOT, whichever comes first). 
• Safety assessment: monitoring and recording all adverse events and serious adverse 
events using the CTCAE version 5.0 
• Review of concomitant medications 
 
9.5 
Follow-up Evaluations Q 90 days (± 14 days) 
Survival follow-up, including survival status and post-study treatments. Follow-up may be 
conducted via phone call or record review if laboratory assessments are not required. 
• Laboratory assessments:  
o If treatment is discontinued prior to PSA progression, PSA testing will continue throughout 
follow-up until PSA progression or start of another treatment. Patients who have PSA 
progression prior to discontinuing treatment do not need to have PSA testing performed 
during follow-up.  
10 CRITERIA FOR EVALUATION AND ENDPOINT 
10.1 
Efficacy 
Patients must receive one full cycle of rucaparib and have PSA assessed after that cycle to be 
evaluable for efficacy. Patients who do not meet evaluable criteria will be replaced. 
PSA levels will be monitored monthly while on treatment for comparison to baseline levels 
with the objective of assessing the proportion of patients with a 50% reduction in PSA levels 
(PSA50).  
PSA progression-free survival (PSA-PFS) is defined as the time from study enrollment until 
the time of PSA progression as defined by PCWG322 criteria or death.  
Patients who start another anti-cancer treatment prior to PSA progression or who complete 
one year of follow-up without PSA progression will have their data censored at that time 
point. 
Overall survival is defined as the time from study enrollment until death. Survival will be 
monitored while on study and every 90 days for 2 years after study discontinuation.  
10.2 
Safety 
Routine safety and tolerability will be evaluated from the results of reported signs and 
symptoms, scheduled physical examinations, vital sign measurements, and clinical laboratory 
test results. More frequent safety evaluations may be performed if clinically indicated or at 
the discretion of the investigator.  
 Physical Examination 
Complete and symptom-directed physical examinations will be performed by a licensed 
physician or appropriately delegated personnel as noted in the calendar (Section 8). 


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 Vital Signs 
Vital signs (weight, blood pressure, respiratory rate, pulse rate and temperature) will be 
obtained as noted in the calendar (Section 8).  
 Safety Laboratory Determinations 
Laboratory evaluations will be performed as noted in the calendar (Section 8).  
10.3 
Stopping Rules 
The protocol has no formal stopping rules. 
11 STATISTICAL CONSIDERATIONS 
11.1 
Primary Objective 
The total sample size is 15 patients. The null hypothesis is that median PSA-PFS is 3 months.  
With an alternative hypothesis that median PSA-PFS is 12 months, and assuming PSA-PFS 
is exponentially distrubuted, a sample size of 15 provides 90% power at one-sided alpha = 
0.05. The median progression-free survival in the PROfound trial of olaparib treated patients 
was 7.4 months for Arm A (ie paitents with BRCA1, BRCA2 or ATM alterations). This trial 
evaluated patients who’s cancer was highly refractory and had more advanced disease. The 
median PFS in the TOPARP-A trial was 9.8 months in biomarker selected patients. In the 
ROAR trial, the patients have early disease which is hypothesized to be more responsive to 
treatment. We hypothesize that the median PFS will be longer than that observed in prior 
studies where olaparib was tested in a more advanced setting.  
11.2 
Secondary Objectives 
Descriptive analysis methods will be used to analyze tabulated safety characteristics. Kaplan-
Meier methods and associated confidence intervals will also be used to analyze PSA 
progression-free survival and OS. The proportion of subjects who achieve PSA50 will be 
reported along with a 95% confidence interval. The proportion of subjecs with an 
undetectable PSA after initiation of PARP therapy at 6 and 12 months will be assessed using 
Kaplan-Meier methods and associated confidence intervals. The proportion of subjects who 
exhibit an objective response will be reported along with an exact binomial confidence 
interval. 
11.3 
Exploratory Objectives 
Descriptive methods will be used to analyze the exploratory objectives. Circulating tumor 
DNA alterations and response category will be cross-tabulated. The mean and standard 
deviation of enumerated tumor cell characteristics will be reported separately for each 
response category. The mean and standard deviation at the time of radiographic progression 
will be reported for subjects with documented radiographic progression. 


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12 REGISTRATION GUIDELINES 
Patients must meet all of the eligibility requirements listed in Section 5 prior to 
registration. 
Study related screening procedures can only begin once the patient has signed a consent 
form. Patients must not begin protocol treatment prior to registration. 
Treatment should start within five working days after registration. 
To register eligible patients on study, complete a Clinical Trials Office Patient Registration Form 
and submit to CTORegistrations@hci.utah.edu. 
13 DATA SUBMISSION SCHEDULE 
The Case Report Forms (CRFs) are a set of (electronic or paper) forms for each patient that 
provides a record of the data generated according to the protocol. CRF’s should be created prior 
to the study being initiated and updated (if applicable) when amendments to the protocol are IRB 
approved. These forms will be completed on an on-going basis during the study. The medical 
records will be source of verification of the data. During the study, the CRFs will be monitored 
for completeness, accuracy, legibility and attention to detail by a member of the Research 
Compliance Office. The CRFs will be completed by the Investigator or a member of the study 
team as listed on the Delegation of Duties Log. The data will be reviewed no less than annually 
by the Data and Safety Monitoring Committee. The Investigator will allow the Data and Safety 
Monitoring Committee or Research Compliance Office personnel access to the patient source 
documents, clinical supplies dispensing and storage area, and study documentation for the above-
mentioned purpose. The Investigator further agrees to assist the site visitors in their activities. 
14 SPECIAL INSTRUCTIONS  
14.1 
Correlative Studies 
To support exploratory objectives and correlative studies, blood and tissue samples will be 
collected at the time points indicated on the Schedule of Events. After completion of the 
described correlative studies, any remaining blood or tissue will be stored for future 
unspecified cancer research. With the participant’s approval and as approved by the 
Institutional Review Board (IRB), de-identified biological samples will be stored at 
Huntsman Cancer Institute’s Biorepository.  
At the time of consent, subjects will be given the opportunity to authorize the biobanking of 
their remaining samples for use in future undisclosed research. During the conduct of the 
study, an individual participant can choose to withdraw consent to have biological specimens 
stored for future research. However, the withdrawal of consent with regard to biosample 
storage may not be possible after the study is completed. 
Correlative studies will evaluate exploratory biomarkers predictive of response and resistance 
to treatment with rucaparib. Patients will have a baseline assessment at the time of 
enrollment.  


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 Collection of Blood for Correlative Analysis 
30-40 mL of blood will be collected at screening, C3D1, C7D1, and confirmed PSA 
Progression or EOT (whichever occurs first).  
Testing may include, but is not limited to: 
• Circulating tumor cells (CTC) detection, enumeration, and characterization 
• Cytokine/chemokine/interferon assays 
• Genomic analysis 
• Proteomic analyses 
• Flow Cytometry 
Specimen collection and processing instructions can be found in the lab manual. 
 Collection of Urine samples for Correlative Analysis 
For patients with an intact prostate, 10-20 mLs of urine will be collected at screening, C3D1, 
C7D1, and confirmed PSA progression or EOT (whichever occurs first). Prior to collection 
of the urine specimen a prostate exam will be performed by the treating physician. 
Testing may include, but is not limited to: 
• Androgen receptor isoform splice variant (AR-V7). 
Specimen collection and processing instructions can be found in the lab manual. 
 Collection of Tumor Tissue 
Available archival tissue will be used for correlative testing. If archival tissue is not 
available, a new biopsy will NOT be required. Archival tissue slides should not be cut until 
requested by the central lab.  
An optional fresh biopsy will be obtained at the PSA Progression Confirmation Visit only for 
subjects who demonstrate radiographic progression. Up to 6 cores will be obtained.  
Testing may include, but is not limited to: 
• 
Multiomics platforms 
• 
Immunohistochemistry 
• 
Flow cytometry  
Instructions for processing and analysis will be detailed in the lab manual. 
 BRCAness Testing 
Genomic or genetic testing for ‘BRCAness’ will be confirmed with either blood or tissue 
based testing.  
 


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15 ETHICAL AND REGULATORY CONSIDERATIONS 
15.1 
Informed consent  
Informed consent will be obtained from all research participants prior to performing any 
study procedures using the most recent IRB approved version.  
15.2 
Human Subjects Protections 
 Participation of Children 
Patients must be at least 18 years of age to participate. 
 Participation of Subjects Unable To Give Consent 
Patients must be able to provide informed consent and willing to sign an approved consent 
form that conforms to federal and institutional guidelines. 
15.3 
Institutional Review 
Before study initiation, the investigator must have written and dated approval/favorable 
opinion from the IRB/IEC for the protocol, consent form, subject recruitment materials (eg, 
advertisements), and any other applicable patient-facing documents. The investigator should 
also provide the IRB/IEC with a copy of the Investigator Brochure or product labeling 
information. 
The investigator or designee should provide the IRB/IEC with reports, updates and other 
information (e.g., expedited safety reports, amendments, and administrative letters) according 
to regulatory requirements or institution procedures. Data and Safety Monitoring Plan 
A Data and Safety Monitoring Committee (DSMC) is established at Huntsman Cancer 
Institute (HCI) to ensure the well-being of patients enrolled on Investigator Initiated Trials 
that do not have an outside monitoring review. The roles and responsibilities of the DSMC 
are set forth in the NCI-approved Data and Safety Monitoring (DSM) plan. The activities of 
the committee include reviewing adverse events (including SAEs), deviations, important 
medical events, significant revisions or amendments to the protocol, and approving 
cohort/dose escalations. If the DSMC and/or the PI have concerns about unexpected safety 
issues, the study will be stopped and will not be resumed until the issues are resolved. The 
DSMC also reviews and approves audit reports generated by the Research Compliance 
Office. 
This is a Phase II study classified as moderate risk per the NCI-approved DSM plan. Each 
moderate risk study may be assigned a physician member of the DSMC as medical monitor, 
or in rare cases, an external medical monitor. The medical monitor will be notified of all 
serious adverse events (SAEs). SAEs occurring in patients treated at HCI or its affiliates will 
also be reviewed by the full DSMC monthly. The full committee will also review all 
toxicities for patients on treatment and within 30 days of their last treatment on a quarterly 
basis.  
Each moderate-risk study will be assigned a dedicated research compliance officer who will 
monitor the trial. Moderate-risk trials will be monitored by RCO personnel after the first 
patient is enrolled and every six months thereafter during active enrollment. The RCO 


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monitor will review the study status and summarize enrollment, toxicities, SAEs, dose 
escalation, statistical endpoints (e.g., stopping rules), deviations, etc. for the full DSMC 
membership at the regularly scheduled meetings. Amendments that increase risk, change 
dosing, or impact study objectives will be reviewed by the DSMC and approved by the 
PRMC and IRB. Moderate-risk trials will be formally reviewed by the DSMC after the first 
patient is enrolled and then semi-annually thereafter.  
An initial audit of moderate-risk studies will be conducted by the RCO approximately one 
year after enrollment begins and annually thereafter. Audits of moderate-risk studies may be 
conducted more frequently as requested by the DSMC, IRB, PRMC, RCO management, or 
the PI. 
15.4 
Adverse Events / Serious Adverse Events 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) 
Version 5.0 for AE and SAE reporting. 
 Adverse Events (AE) 
An adverse event is the appearance or worsening of any undesirable sign, symptom, or 
medical condition occurring after starting the study drug even if the event is not considered 
to be related to study drug. For the purposes of this study, the terms toxicity and adverse 
event are used interchangeably. Medical conditions/diseases present before starting study 
drug are only considered adverse events if they worsen after starting study drug. Abnormal 
laboratory values or test results constitute adverse events only if they induce clinical signs or 
symptoms, are considered clinically significant, or require therapy. 
Collection of adverse events will begin after the first dose of study treatment and end 30 days 
after the last dose of study treatment.  
Information about all adverse events, whether volunteered by the subject, discovered by 
investigator questioning, or detected through physical examination, laboratory test or other 
means, will be collected and recorded and followed as appropriate. 
The occurrence of adverse events should be sought by non-directive questioning of the 
patient at each visit or phone contact during the study. Adverse events also may be detected 
when they are volunteered by the patient during or between visits or through physical 
examination, laboratory test, or other assessments. As far as possible, each adverse event 
should be evaluated to determine: 
1. The severity grade based on CTCAE v.5.0 (grade 1-5) 
2. Its relationship to the study drug(s) (definite, probably, possible, unlikely, not related) 
3. Its duration (start and end dates or if continuing at final exam) 
4. Action taken (no action taken; study drug dosage adjusted/temporarily interrupted; 
study drug permanently discontinued due to this adverse event; concomitant 
medication taken; non-drug therapy given; hospitalization/prolonged hospitalization) 
5. Whether it constitutes an SAE 
All adverse events will be treated appropriately. Such treatment may include changes in 
study drug treatment as listed in the dose modification section of this protocol (see Section 


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7.1 for guidance). Once an adverse event is detected, it should be followed until a new 
baseline is reached, death, or when patient is lost to follow up. Assessment should be made at 
each visit (or more frequently, if necessary) of any changes in severity, the suspected 
relationship to the study drug, the interventions required to treat it, and the outcome. 
Information about common side effects already known about the rucaparib is described in the 
Drug Information section (Section 3) as well as Section 6.6 and Table 19 of Investigator 
Brochure. This information will be included in the patient informed consent and will be 
discussed with the patient during the study as needed. 
All adverse events will be immediately recorded in the patient research chart.  
 Serious Adverse Event (SAE) 
Information about all serious adverse events will be collected and recorded. A serious 
adverse event is an undesirable sign, symptom or medical condition which: 
• Is fatal or life-threatening 
• Results in persistent or significant disability/incapacity 
• Is medically significant, i.e., defined as an event that jeopardizes the patient or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
• Causes congenital anomaly or birth defect 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
o Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition (procedures such as central line placements, 
paracentesis, pain control) 
o Elective or pre-planned treatment for a pre-existing condition that is unrelated to 
the indication under study and has not worsened since the start of study drug 
o Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission > 24 
hours.  
o Social reasons and respite care in the absence of any deterioration in the patient’s 
general condition 
Collection of adverse events will begin after the first dose of study treatment and end 30 days 
after the last dose of study treatment.  
Any death (except those due to progression of disease) from any cause while a patient is 
receiving treatment on this protocol or up to 30 days after the last dose of protocol treatment, 
or any death which occurs more than 30 days after protocol treatment has ended but which is 
felt to be treatment related, must be reported. 
Toxicities which fall within the definitions listed above must be reported as an SAE 
regardless if they are felt to be treatment related or not. Toxicities unrelated to treatment that 
do NOT fall within the SAE definitions above or AESIs in section 15.5.3 must simply be 
documented as AEs in the patient research chart.  


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 Adverse Events of Special Interest 
AESIs (serious or nonserious) are defined as AEs of scientific and medical concern specific 
to the Clovis’s product or program, for which ongoing monitoring and rapid communication 
by the investigator to Clovis can be appropriate. Such an event might warrant further 
investigation in order to characterize and understand it. Depending on the nature of the event, 
rapid communication by the Sponsor-Investigator to other parties (e.g., regulators) might also 
be warranted. 
Details on Clovis’s currently agreed list of AESIs for rucaparib can be found in the current 
rucaparib IB. These AESIs are to be reported to Clovis expeditiously within 48 hours of 
knowledge of the event, during the study through 30 days after receiving the last dose of 
study treatment, according to the procedures below. 
15.5 
SAE Reporting Requirements 
SAEs must be reported to the DSMC, the FDA, the IRB, and drug manufacturer according to 
the requirements described below: 
A MedWatch 3500A form must be completed and submitted to HCI-RCO@utah.edu as soon 
as possible, but no later than 1 business day after first knowledge or notification of event. 
DSMC Notifications: 
An HCI Research Compliance Officer (RCO) will process and submit the MedWatch form to 
the proper DSMC member as necessary for each individual study.  
The RCO will summarize and present all reported SAEs according to the Data and Safety 
Monitoring Plan at the quarterly DSMC meeting. 
FDA Notifications: 
This study is IND exempt; therefore, there are no SAE reporting requirements to the FDA 
IRB Notification: 
Events meeting the University of Utah IRB or local IRB reporting requirements will be 
submitted per local guidelines. 
Drug Manufacturer Notifications: 
All SAEs and AESIs, regardless of relationship to study drug, must be reported to Clovis 
Pharmacovigilance within 24 hours of knowledge of the event, during the study through 30 
days after receiving the last dose of study treatment, according to the procedures below. After 
the 30 day specified window, only SAEs considered to be treatment related and all AESIs, 
regardless of treatment relationship, should be reported. It is important that the investigator 
provide an assessment of relationship of the SAE or AESI to study treatment at the time of 
the initial report. 
Reporting will be done via email: drugsafety@clovisoncology.com. 


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15.6 
Reporting of Pregnancy  
Although pregnancy is not considered an adverse event, it is the responsibility of 
investigators or their designees to report any pregnancy or lactation in a subject, including 
the pregnancy of a male subjects’ female partner as an SAE. Pregnancies or lactation that 
occurs during the course of the trial or with 6 months of completing the trial or starting 
another new anticancer therapy, whichever is earlier, must be reported to the DSMC, IRB, 
FDA, and the sponsor as applicable. All subjects and female partners who become pregnant 
must be followed to the completion/termination of the pregnancy. Pregnancy outcomes of 
spontaneous abortion, missed abortion, fetal death, intrauterine death, miscarriage and 
stillbirth must be reported as serious events.  
15.7 
Protocol Amendments 
Any amendments or administrative changes to an IRB approved protocol will not be initiated 
without submission of an amendment for IRB review and approval.  
These requirements for approval will in no way prevent any immediate action from 
being taken by the investigator in the interests of preserving the safety of all patients 
included in the trial.  
Any amendments to the protocol that significantly affect the safety of subjects, scope of 
the investigation, or the scientific quality of the study are required to submit the 
amendment for FDA review. 
15.8 
Protocol Deviations 
A protocol deviation (or violation) is any departure from the defined procedures and 
treatment plans as outlined in the protocol version submitted and previously approved by the 
IRB. Protocol deviations have the potential to place participants at risk and can also 
undermine the scientific integrity of the study thus jeopardizing the justification for the 
research. Protocol deviations are unplanned and unintentional events.  
Because some protocol deviations pose no conceivable threat to participant safety or 
scientific integrity, reporting is left to the discretion of the PI within the context of the 
guidelines below. The sponsor requires the prompt reporting  to HCI RCO of protocol 
deviations which are: 
• Exceptions to eligibility criteria. 
• Intended to eliminate apparent immediate hazard to a research participant or  
• Harmful (caused harm to participants or others, or place them at increased risk of 
harm - including physical, psychological, economic, or social harm), or  
• Possible serious or continued noncompliance  
15.9 
FDA Annual Reporting 
This study is IND exempt therefore there are no annual reporting requirements to the FDA.   


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15.10 Clinical Trials Data Bank 
The study will be registered on http://clinicaltrials.gov and the NCI CTRP (Clinical Trials 
Reporting Program) by the Clinical Trials Office. 
15.11 Record Keeping 
Per 21 CFR 312.57, Investigator records shall be maintained for a period of 2 years following 
the date a marketing application is approved; or, if no application is filed or the application is 
not approved, until 2 years after the investigation is discontinued and the FDA is notified. 


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16 BIBLIOGRAPHY 
1. Higano CS: Intermittent versus continuous androgen deprivation therapy. J Natl Compr Canc 
Netw 12:727-33, 2014 
2. de Bono JS, Logothetis CJ, Molina A, et al: Abiraterone and increased survival in metastatic 
prostate cancer. N Engl J Med 364:1995-2005, 2011 
3. Beer TM, Armstrong AJ, Rathkopf DE, et al: Enzalutamide in metastatic prostate cancer 
before chemotherapy. N Engl J Med 371:424-33, 2014 
4. Tannock IF, de Wit R, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus 
prednisone for advanced prostate cancer. N Engl J Med 351:1502-12, 2004 
5. Parker C, Nilsson S, Heinrich D, et al: Alpha emitter radium-223 and survival in metastatic 
prostate cancer. N Engl J Med 369:213-23, 2013 
6. Sweeney CJ, Chen YH, Carducci M, et al: Chemohormonal Therapy in Metastatic Hormone-
Sensitive Prostate Cancer. N Engl J Med 373:737-46, 2015 
7. Duchesne GM, Woo HH, Bassett JK, et al: Timing of androgen-deprivation therapy in 
patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 
[TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol 17:727-37, 
2016 
8. Hershman DL, Unger JM, Wright JD, et al: Adverse Health Events Following Intermittent 
and Continuous Androgen Deprivation in Patients With Metastatic Prostate Cancer. JAMA 
Oncol 2:453-61, 2016 
9. Lord CJ, Ashworth A: BRCAness revisited. Nat Rev Cancer 16:110-20, 2016 
10. Cancer Genome Atlas Research N: The Molecular Taxonomy of Primary Prostate Cancer. 
Cell 163:1011-25, 2015 
11. Pritchard CC, Mateo J, Walsh MF, et al: Inherited DNA-Repair Gene Mutations in Men with 
Metastatic Prostate Cancer. N Engl J Med 375:443-53, 2016 
12. Castro E, Goh C, Olmos D, et al: Germline BRCA mutations are associated with higher risk 
of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J 
Clin Oncol 31:1748-57, 2013 
13. Bancroft EK, Page EC, Castro E, et al: Targeted prostate cancer screening in BRCA1 and 
BRCA2 mutation carriers: results from the initial screening round of the IMPACT study. Eur 
Urol 66:489-99, 2014 
14. Castro E, Goh C, Leongamornlert D, et al: Effect of BRCA Mutations on Metastatic Relapse 
and Cause-specific Survival After Radical Treatment for Localised Prostate Cancer. Eur Urol 
68:186-93, 2015 
15. Mateo J, Carreira S, Sandhu S, et al: DNA-Repair Defects and Olaparib in Metastatic 
Prostate Cancer. N Engl J Med 373:1697-708, 2015 
16. Mukhopadhyay A, Elattar A, Cerbinskaite A, Wilkinson SJ, Drew Y, Kyle S, et al. 
Development of a functional assay for homologous recombination status in primary cultures 
of epithelial ovarian tumor and correlation with sensitivity to poly(ADP-ribose) polymerase 
inhibitors. Clin Cancer Res. 2010;16(8):2344-51. 


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17. Goggins M, Schutte M, Lu J, Moskaluk CA, Weinstein CL, Petersen GM, et al. Germline 
BRCA2 gene mutations in patients with apparently sporadic pancreatic carcinomas. Cancer 
Res. 1996;56(23):5360-4. 
18. Drew Y, Plummer R. The emerging potential of poly(ADP-ribose) polymerase inhibitors in 
the treatment of breast cancer. Curr Opin Obstet Gynecol. 2010;22(1):67-71. 
19. Pellegata NS, Sessa F, Renault B, Bonato M, Leone BE, Solcia E, et al. K-ras and p53 gene 
mutations in pancreatic cancer: ductal and nonductal tumors progress through different 
genetic lesions. Cancer Res. 1994;54(6):1556-60. 
20. Kim G, Ison G, McKee AE, Zhang H, Tang S, Gwise T, et al. FDA Approval Summary: 
Olaparib Monotherapy in Patients with Deleterious Germline BRCA-Mutated Advanced 
Ovarian Cancer Treated with Three or More Lines of Chemotherapy. Clin Cancer Res. 
2015;21(19):4257-61. 
21. Niemi M. Transporter pharmacogenetics and statin toxicity. Clin Pharmacol Ther. 
2010;87(1):130-3. 
22. Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, 
Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, 
Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, 
Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz 
LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. 
Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated 
Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 
2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22. 


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APPENDIX A — Rucaparib Dosing Diary 
Page 1/2
Patient Initials: _____________________ 
Treatment Cycle #: __________________ 
Patient Study ID: __________________ 
Dose: ____________________________
1) Take the number of pills prescribed by your study doctor twice a day at approximately the 
same time each day. Take your pills with an 8oz glass of water with or without food.  
2) If you forget to take your pills at the right time, you can take them as soon as you remember 
on that day as long as it’s not more than 4 hours after the usual time.  
3) If you miss taking your pills by more than 4 hours, the dose is missed. Do not take extra 
pills with your next dose to try and make up for the missed dose.  
4) Complete one line of the diary each day and write the total number of pills taken in the 
morning and in the evening. If you’ve missed a dose, briefly explain why in the comments. 
5) Please bring this diary as well as all empty containers and any unused supplies to your next 
clinic visit.  
 
Day 
Date 
mm/dd/yy 
Morning dose 
hh:mm 
Evening dose 
hh:mm 
Number of Pills 
Taken 
Comments 
Day 1  
 
 
 
 
 
Day 2 
 
 
 
 
 
Day 3 
 
 
 
 
 
Day 4 
 
 
 
 
 
Day 5 
 
 
 
 
 
Day 6 
 
 
 
 
 
Day 7 
 
 
 
 
 
Day 8 
 
 
 
 
 
Day 9 
 
 
 
 
 
Day 10 
 
 
 
 
 
Day 11 
 
 
 
 
 
Day 12 
 
 
 
 
 
Day 13 
 
 
 
 
 
Day 14 
 
 
 
 
 
Day 15 
 
 
 
 
 
 
 


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APPENDIX A - Rucaparib Dosing Diary 
Page 2/2
Patient Initials: ______________________ 
Treatment Cycle #: __________________ 
Patient Study ID: __________________ 
Dose: ____________________________
1) Take the number of pills prescribed by your study doctor twice a day at approximately the 
same time each day. Take your pills with an 8oz glass of water with or without food.  
2) If you forget to take your pills at the right time, you can take them as soon as you remember 
on that day as long as it’s not more than 4 hours after the usual time.  
3) If you miss taking your pills by more than 4 hours, the dose is missed. Do not take extra 
pills with your next dose to try and make up for the missed dose.  
4) Complete one line of the diary each day and write the total number of pills taken in the 
morning and in the evening. If you’ve missed a dose, briefly explain why in the comments. 
5) Please bring this diary as well as all empty containers and any unused supplies to your next 
clinic visit.  
Day 
Date 
mm/dd/yy 
Morning dose 
hh:mm 
Evening dose 
hh:mm 
Number of Pills Taken 
Comments 
Day 16 
 
 
 
 
 
Day 17 
 
 
 
 
 
Day 18 
 
 
 
 
 
Day 19 
 
 
 
 
 
Day 20 
 
 
 
 
 
Day 21 
 
 
 
 
 
Day 22 
 
 
 
 
 
Day 23 
 
 
 
 
 
Day 24 
 
 
 
 
 
Day 25 
 
 
 
 
 
Day 26 
 
 
 
 
 
Day 27 
 
 
 
 
 
Day 28 
 
 
 
 
 
Day 29 
 
 
 
 
 
Day 30 
 
 
 
 
 
Day 31 
 
 
 
 
 
Patient Signature ____________________________________ Date______________________ 
 
 


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APPENDIX B – PROSTATE CANCER CLINICAL TRIALS WORKING GROUP 3 
(PCWG3) 
The PCWG3 was created to more accurately assess bone lesions and to describe PSA based 
progression. PCWG3 rules were designed to be used in conjunction with radionuclide (90mTc) 
bone scintigraphy and therefore should be used for all bone response assessments. Only bone 
lesions seen on bone scans will be followed for assessment of response.  
Bone Assessments 
Baseline Assessment 
All bone lesions may be recorded as non-target lesions only and the number of lesions 
should be noted. 
Response Assessment 
While on treatment, follow-up scans should be assessed for progressive disease (PD), 
progressive disease unconfirmed (P Du), no progressive disease (Non-PD), no evidence 
of disease (NED), or non-evaluable (NE). 
Table 1: Bone response assessment categories 
Bone Response 
Definition 
PD 
2 new lesions, not flare, persistent 
P Du 
2 new lesions, but confirmation is required by the second scan. The 
temporary marker of PD should be updated to PD or non-PD upon 
subsequent scans. 
If P Du is determined on the last scan, sponsor should update to PD upon 
analysis. 
Non-PD 
At least 1 bone lesion present, but not enough to trigger PD. 
NE 
Status of bone lesions cannot be determined. 
NED 
No lesions are seen on bone scan (either none at baseline or all have 
resolved). 
Rules of Progressive Disease 
• 2+2 Rule: If 2 new lesions appear on the first scan after the initiation of treatment, 
the response is classified as P Du and another scan is performed ≥ 6 weeks. 
o If the next scans show at least 2 new bone lesions in addition to those seen 
in the prior scan, the prior scan is to be considered confirmed PD. 
o If the next scan does not show at least 2 additional new bone lesions the 
lesions seen on the prior scan are considered pre-existing lesions. The 
bone response on the prior scan is updated to non-PD and new lesions 
seen on the first scan are ignored. 
• Once outside of the flare window (the first 12 weeks of treatment) the appearance 
of new lesions must be confirmed with a second scan ≥ 6 weeks after the first 
scan. 


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o If ≥ 2 new lesions appear on a scan the scan will be classified as P Du 
until a second scan confirms lesion persistence.  
 If lesions are persistent on the second scan, the prior response will 
be updated to PD. 
 If the lesions disappeared on the second scan, the prior response is 
updated to non-PD. 
• If 1 new bone lesion is seen on one scan classifying the scan as non-PD, but the 
following scan shows an additional new lesion (2 new lesions total between 
subsequent scans) the second scan will be classified as PD. 
• Diffuse skeletal tumor involvement may result in a superscan. In this case, 
distinguishing between individual new bone lesions may be impossible. If a 
superscan occurs after baseline, the response will be considered PD and no further 
confirmation scans are required. 
PSA Progression 
PSA should be monitored at the beginning of every cycle. Any rise in PSA during the first 12 
weeks of treatment should be monitored but should not be deemed evidence of progression. 
Record the percent change from baseline at 12 weeks. After a decline from baseline: record time 
from start of therapy to first PSA increase that is ≥ 25% and ≥ 2 ng/mL above the nadir, and 
which is confirmed by a second value ≥ 3 weeks later (i.e., a confirmed rising trend). 
Nodal and Soft Tissue Progression 
Nodal and soft tissue documentation, tracking, and determination of progression will follow 
RECIST 1.1.