Clinical trial: NCT03179410
Section: Alternatives
Subsections: Are There Benefits To Taking Part In The Study?|What Alternatives Are There To Participation In This Study?

There is no guarantee that you will receive any direct medical benefits from this study. If the study drug is effective and safe, it may help your immune system stop, slow or reverse the growth of tumors. Your overall health may improve, stay the same, or even worsen while on this study. Information from this study may help doctors learn more about avelumab and the treatment of neuroendocrine prostate cancer. This information may benefit other patients with prostate cancer or a similar condition in the future.

If you decide not to take part in this study, other approved treatments are available to you, which the study doctor will explain to you. You may receive treatment to control the symptoms you may be having as a result of your disease. Other options may include chemotherapy and radiation therapy. You may also choose to have no treatment for your cancer; receiving only palliative care to manage your symptoms and make you feel more comfortable. Study staff will discuss these alternative treatments and the risks and benefits associated with these treatments with you before you take part in this study. Please talk to your doctor about these and perhaps other options.
Clinical trial: NCT03179410
Section: Confidentiality
Subsections: Will My Information Be Kept Confidential?

Participation in research involves some loss of privacy. We will do our best to make sure that information about you is kept confidential, but we cannot guarantee total confidentiality. Your personal information may be viewed by individuals involved in this research and may be seen by people including those collaborating, funding, and regulating the study. We will share only the minimum necessary information in order to conduct the research. Your personal information may also be given out if required by law. In addition, your records may be reviewed in order to meet federal or state regulations. Reviewers may include representatives from the Food and Drug Administration, representatives of Pfizer, representatives of the Duke Cancer Institute, the Duke Office of Audit, Risk, and Compliance, the Duke University Health System Institutional Review Board, and others as appropriate. If any of these groups review your research record, they may also need to review your entire medical record. If this information is disclosed to outside reviewers for audit purposes, it may be further disclosed by them and may not be covered by federal privacy regulations. Duke is participating in this study along with other member institutions of the Prostate Cancer Clinical Trial Consortium (PCCTC). As part of their reporting requirements, we will report to the PCCTC the  P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
following information about all subjects that we enroll on this study: subject ID, consent date, race, and ethnicity. As part of this study, you will be asked to have certain tests and/or procedures performed. Some of these tests and/or procedures would have been done as part of your regular care. The study doctor will use these test results both to treat you and to complete this research. These test results will be recorded in your medical record and will be reported to the research data office at Duke. Some information collected about you only for this research study may be kept in a research study record separate from your medical record, and some research information may also be part of your medical record. You will not have access to this research information until the end of the study. However, it will be available to your physicians if needed for your care. The study results will be retained in your research record for at least six years after the study is completed. At that time either the research information not already in your medical record may be destroyed or information identifying you will be removed from such study results at DUHS. Any research information in your medical record will be kept indefinitely. While the information and data resulting from this study may be presented at scientific meetings or published in a scientific journal, your identity will not be revealed. Some people or groups who receive your health information might not have to follow the same privacy rules. Once your information is shared outside of DUHS, we cannot guarantee that it will remain private. If you decide to share private information with anyone not involved in the study, the federal law designed to protect your health information privacy may no longer apply to the information you have shared. Other laws may or may not protect sharing of private health information.
Clinical trial: NCT03179410
Section: Duration of Study Involvement
Subsections: Active On-Study Phase|Day 1 Of Every Cycle|Day 15 Of Every Cycle|End Of Study Visit|Safety Follow-Up Visit|Long Term Follow-Up|How Long Will I Be In This Study?

During this part of the study, your study doctor will determine if you will continue receiving your standard of care treatment of androgen deprivation therapy and/or enzalutamide. You will also begin receiving intravenous (IV) administration (using a needle placed into your vein) of the study drug avelumab every 2 weeks. One cycle lasts 4 weeks so you will receive 2 infusions per cycle. Your doctor may prescribe you steroids or cromolyn to take prior to avelumab. These medications may reduce your risk of side effects, such as allergic reactions, while you are being give the avelumab. They may be taken by mouth (such as dexamethasone or cromolyn) or inhaled (such as cromolyn). Your doctor will tell you if taking pre-medications is appropriate for you. In addition to the procedures listed below, you will have a bone scan and CT/MRI or a PET/CT scan every 8 weeks while you are receiving the study drug, which is the standard of care for evaluating your  
 P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
type of cancer. Some of the tests or procedures listed below may also be part of your regular medical care and may be done even if you do not take part in the study.

Physical exam, including measurement of your weight, height and vital signs.  
Review of current medications that you are taking Review of any adverse events you may be experiencing Collection of blood samples (about 3 tablespoons) for routine laboratory tests (including blood cell counts, blood chemistry, and thyroid function), tests to measure your prostate-specific antigen (PSA) level and testosterone level, and tests to measure tumor markers (CEA and chromogranin A)
Collection of blood samples (about 4 tablespoons) for research **(cycle 1 and cycle 3 only):**
Several tests will be performed on the blood collected for research including but not limited to genetic sequencing and tests for biomarkers. These tests will help the researchers learn more about the effect that avelumab has on your cancer and your immune system.  
**Quality of Life assessment**: You will complete a questionnaire about your quality of life o You will complete this questionnaire on Day 1 of cycles 1, 4, 7 and every 3 subsequent cycles You will receive avelumab by IV infusion

Physical exam, including measurement of your weight, height and vital signs.  
Review of current medications that you are taking Review of any adverse events you may be experiencing Collection of blood samples (about 1.5 tablespoons) for routine laboratory tests (including blood cell counts, blood chemistry)
You will receive avelumab by IV infusion

An End of Study visit will be scheduled no more than 7 days after your last dose of study drug. At this visit, the following procedures will be performed:
Physical exam, including measurement of your weight, height and vital signs.  
Review of current medications that you are taking Review of any adverse events you may be experiencing  
 P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
Collection of blood samples (about 3 tablespoons) for routine laboratory tests (including blood cell counts, blood chemistry, and thyroid function), tests to measure your prostate-specific antigen (PSA) level and testosterone level, and tests to measure tumor markers (CEA and chromogranin A)
Collection of blood samples (about 4 tablespoons) for research tests o These samples will be collected at this visit or when your cancer progresses, whichever occurs first.  
Tumor assessment using bone scan and CT/MRI scan or a PET/CT
Quality of Life assessment

A safety follow-up visit will be scheduled about 28 days after your last dose of study drug. At this visit, the following procedures will be performed:
DUHS IRB IRB NUMBER: Pro00080869  
 P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
Physical exam, including measurement of your weight, height and vital signs.  
Review of current medications that you are taking Review of any adverse events you may be experiencing Collection of blood samples (about 2 tablespoons) for routine laboratory tests (including blood cell counts, blood chemistry, and thyroid function), and tests to measure your prostate-specific antigen (PSA) level and testosterone level

Following the end of your study regimen, your study doctor (or an appointed delegate) will contact you or your family or caregiver, or may access your medical records every 3 months to determine your longterm health status and to collect additional information. If you decide you no longer want to be contacted or allow access to your medical records for follow-up information, tell your study doctor.

You will continue to receive the study drug as long as you receive clinical benefit. This means you may also have the option to continue receiving the study drug even if your PSA level rises or your cancer appears to grow on imaging scans. Your study doctor will discuss this option with you in more detail.  
When you stop receiving the study drug, you will continue to be followed every 3 months (up to 3 years) for survival. You can choose to stop participating at any time without penalty or loss of any benefits to which you are entitled. However, if you decide to stop participating in the study, we encourage you to talk to your doctor first.
Clinical trial: NCT03179410
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Are The Risks Of The Study?|Risks Associated With Avelumab|Risks Of Antihistamines|Risks Of Steroids|Risks Of Cromolyn|Reproductive Risks For Males|Risks Of Biopsy:|Risks Of Radiation:|Drug And Food Interactions:|What About Research Related Injuries?

Participation in a clinical trial is associated with some risks, which may include things that could make you feel unwell, uncomfortable, or harm you. You might have side effects related to the study drug while taking part in the study. Every patient taking part in the study will be closely watched for any side effects; however, the study team does not know all the effects that the study drug may have on you. These side effects may be mild or severe. In some cases, these effects might be long lasting, or permanent, and may be life threatening or in rare cases could result in death. Please refer to your study  
 P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
doctor if you want to have more details on each side effect (such as expected duration, or severity). The clinical study team may give you medicines to help reduce side effects. If any of these side effects occur, you must inform your study doctor immediately.

The following side effects (considered related to study drug) have been observed in 1738 subjects who received avelumab according to the results from one oncology clinical study. Observed in at least 10% of subjects (10 out of 100)
Reactions (including allergic reactions) that occur during or following infusion (may include chills, fever, muscle pain, shortness of breath, low or high blood pressure)
Tiredness Observed in 2-9% of subjects (2-9 out of 100)
Nausea Diarrhea Chills Reduced appetite Joint pain Fever Reduced function of the thyroid gland Itchy skin Vomiting Flu-like symptoms (including body aches, fever, and chills)
Skin rash Increased blood levels of liver enzymes Muscle pain Headache Loss of energy Reactions (including allergic reactions) that occur during or following the infusion (may include chills, fever, muscle pain, shortness of breath, and decrease or increase in blood pressure) are mostly mild or moderate and should resolve with a slowdown or discontinuation of the infusion and administration of medications to control the symptoms such as anti-allergic and pain-killer drugs. In some cases these reactions may be severe (less than 1% of subjects (1 out of 100)) and could require intensive medical support and even life threatening reactions may occur. During the infusion you will be observed closely for signs of an infusion reaction. The drug will be given slowly and you will also be monitored for signs of an infusion reaction for a period of time after the infusion is completed.  
 P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
You may be given drugs to reduce infusion-related reactions (side effects that occur during or following infusion) 30 to 60 minutes prior to receiving avelumab. These drugs may include, but are not limited to, antihistamines, paracetamol, steroids or cromolyn. Your study doctor or nurse will discuss which drugs you will receive and any potential side-effects. Side effects resulting from an increased activity of the immune system have also been observed. Most of these side effects are reversible, which means they will stop once avelumab is discontinued, however in some cases these reactions may be severe (approximately 2% of subjects (2 out of 100)) and could lead to death in rare cases. The reactions that are more severe may require treatment with drugs that decrease the immune system function, also called immunosuppressant drugs (like corticosteroids or more potent drugs, such as infliximab). The side effects resulting from an increased activity of the immune system that were observed in subjects receiving avelumab include the following: Observed in at least 5% of subjects (at least 5 out of 100):
Inflammation of the thyroid gland (could include high or low function of the thyroid gland)
Inflammation of the skin (could include skin rash, itchy skin, redness or blisters)
Observed in 1-5% of subjects (1-5 out of 100):
Inflammation of the large intestine (colitis) Inflammation of the lungs (pneumonitis)
Observed in less than 1% of subjects (less than 1 out of 100):
Inflammation of the liver (hepatitis)
Decreased function of the adrenal gland (adrenal insufficiency)
Inflammation of the muscles (myositis)
Inflammation of the heart (myocarditis)
Inflammation of the eyes (uveitis)
You may be given drugs to reduce infusion-related reactions (side effects that occur during or following infusion) 30 to 60 minutes prior to receiving avelumab. These drugs may include, but are not limited to, antihistamines, paracetamol (Tylenol), steroids or cromolyn.

The most common risks associated with antihistamines are:
Dizziness Dry mouth, nose or throat Loss of coordination Sleepiness DUHS IRB IRB NUMBER: Pro00080869  
 P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
Upset stomach (including loss of appetite, nausea, vomiting, diarrhea and constipation)

The most common side effects of steroids are:
Blurred vision Coughing Changes in mood: feeling of aggression, anxiety or irritability Decrease in the amount of urine Dizziness Dry throat or throat irritation Headache Irregular heartbeat Nausea Numbness or tingling Pounding in the ears Rattling breathing Shortness of breath Swelling of the fingers, hands, feet or lower legs Trouble thinking, speaking or walking Weight gain

The most common side effects of cromolyn are:
Cough Nasal congestion Nausea Sneezing Wheezing Risks of paracetamol The most common side effects of paracetamol are:
Constipation Nausea Vomiting

Your participation in this research may damage your sperm, which could cause harm to a child that you may father while on this study. Such harm may be currently unforeseeable. If you are sexually active, you must agree to use a two medically acceptable forms of birth control (one of which must include a condom as a barrier method of contraception) in order to be in this study and for 2 months after your last DUHS IRB IRB NUMBER: Pro00080869  
 P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
dose of study drug. Medically acceptable contraceptives include: (1) surgical sterilization (such as a vasectomy), or (2) a condom used with a spermicide. Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use. You should inform your partner of the potential for harm to an unborn child. She should know that if pregnancy occurs, you will need to report it to the study doctor, and she should promptly notify her doctor. The study doctor will ask if your partner is willing to provide updates on the progress of the pregnancy and its outcome. If your partner agrees, this information will be provided to Pfizer, Inc. for safety monitoring follow-up.

If you are already having a biopsy that is part of the regular care for your condition, obtaining additional tissue will increase the duration of your procedure. This may lead to a small increase in the chance that you will have an adverse event due to the procedure being performed. The risks of the procedure will depend on the location of the site for biopsy. Biopsies will be performed by a radiologist under radiographic guidance. You will receive local anesthesia (numbing medication). Mild sedation in your vein may be given in some circumstances. The risks of sedation include an allergic reaction, aspiration (fluid going into the lungs), and over sedation. In addition, the IV used may cause a bruise. Rarely, an infection develops at the IV site. When the numbing medication is given, you may initially feel a burning sensation in your skin for several seconds. During the procedure, you may temporarily feel pressure and/or pain of varying degrees. If necessary, you may ask your physician for additional local anesthesia or a medication to ease your stress. You also may experience bleeding and/or bruising after the procedure is completed, and you may experience soreness in the area for a few days afterwards. Rarely, infection can develop. If you have concerns about the overall risk of your biopsy, you should discuss them with your physician.

You will have a number of CT scans, nuclear scans and MRI scans that are part of the regular care for your condition, and you would have them whether or not you participate in this research. These studies will not add to the risk of the research. If you take part in this research and undergo a CT guided biopsy that is part of the regular care for your condition, then these studies will not add to the risk of the research. However, if you have concerns about the overall radiation exposure or MRI safety issues, you should discuss them with your physician.

For your safety, you must tell the study doctor or nurse about all the prescribed medical foods and drugs, herbal products, over-the-counter (OTC) drugs, vitamins, natural remedies, and alcohol that you are DUHS IRB IRB NUMBER: Pro00080869  
 P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
taking before you start the study and before starting to take any of these products while you are on the study. There may be risks, discomforts, drug interactions or side effects that are not yet known.

Immediate necessary medical care is available at Duke University Medical Center in the event that you are injured as a result of your participation in this research study. However, there is no commitment by Duke University, Duke University Health System, Inc., your Duke Physicians or Pfizer, Inc. to provide monetary compensation or free medical care to you in the event of a study-related injury. For questions about the study or research-related injury, contact Dr. Armstrong at during regular business hours and at and ask to have Dr. Armstrong paged after hours and on weekends and holidays.
Clinical trial: NCT03179410
Section: Procedures
Subsections: What Is Involved In The Study?|Optional Post-Progression Biopsy:

If you agree to be in this study, you will be asked to sign this consent form. Before you begin the study, you will need to undergo the following tests or procedures to find out if you are eligible. Some of these tests or procedures may be part of your regular medical care and may be done even if you do not take part in the study. If you have had some of them recently, they may not need to be repeated.  
**Physical exam** including measurement of your weight, height and vital signs **Complete medical history** including review of prior and current medications that you are taking **Performance status** to evaluate how you are able to perform normal activities on a daily basis  
 P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
**Collection of blood samples** (about 3 tablespoons) for routine laboratory tests (including blood cell counts, blood chemistry, and thyroid function), tests to measure your prostate-specific antigen (PSA) level and testosterone level, and tests to measure tumor markers (CEA and chromogranin A)
**Urinalysis:** Your urine will be collected to check for signs of infection, blood, protein or sugar in your urine.  
**Pathology review:** You will be required to submit archival tumor tissue **Tumor imaging:** Your doctor will assess the status of your cancer with standard imaging techniques. These may include a bone scan and a CT/MRI of your chest, abdomen and pelvis, or a PET/CT scan.  
o All sites of your cancer will be scanned using computed tomography (CT) or magnetic resonance imaging (MRI). A CT scan is a type of X-ray that takes images of your body with use of a small amount of radiation. An MRI is a scan that uses radio waves and a strong magnetic field to provide images of internal organs and tissues. The tumor assessment will include a scan of your chest, abdomen, and pelvis. A CT scan of your neck may also be performed if your doctor determines that it is necessary to do so. A bone scan will be done to evaluate the sites where your cancer has spread to the bone.  
o If your study doctor determines it is necessary, you will also have a MRI scan of your brain If eligible to participate, you will be enrolled onto the study and will begin the study visits described below.

Your study doctor may determine that you will undergo a standard of care biopsy after your cancer progresses, meaning you would have the biopsy whether or not you participate in this study. The biopsy tissue may be taken from, but is not limited to, one of the following locations:
Bone marrow Lymph nodes Liver Lung Adrenal gland If you are having a standard of care biopsy, we would like to collect additional tissue for future research tests, including but not limited to genetic sequencing and tests for biomarkers, that will help the researchers learn more about the effect that avelumab has on your cancer and your immune system. In addition, you will be asked for permission to store tissue in the Duke Biospecimen Repository and Processing Core for future research through a separate consent form. Your study nurse will explain the details to you. If you do not want to have this biopsy or you do not want your tissue to be used for the research described in this consent form you will still be able to participate in the main clinical trial. Please read each sentence below and think about your choice. Initial next to either "Yes" or "No" to indicate your choice. If you have any questions, please talk with your study doctor or nurse. ______ "Yes, I give my permission to collect additional tissue from my already planned standard of care (Initial) biopsy, if available." ______ "No, I do not give my permission to collect additional tissue from my already planned standard (Initial) of care biopsy."
Clinical trial: NCT03179410
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

The purpose of this study is to evaluate the safety and efficacy of a drug called avelumab in men with neuroendocrine prostate cancer. This study will investigate how neuroendocrine prostate cancer responds to this drug and what side effects subjects experience. This study will also look different biomarkers to gain a better understanding of how avelumab affects your cancer and immune system. Biomarkers include such things as the proteins involved in tumor growth and immune system activation, circulating tumor cells (CTCs) as well as changes in your DNA. Your genes are made up of DNA. DNA is short for deoxyribonucleic acid. A gene, or DNA, contains information that determines in part the traits, such as eye color, height, or disease risk, that are passed on from parent to child. This study will determine the effect that avelumab has on these biomarkers and your tumors, both before and during the time you receive avelumab by obtaining blood samples, as well as biopsy samples. Avelumab is an antibody (a large, Y-shaped protein used by your body's immune system to identify and neutralize foreign substances such as bacteria, viruses, and tumor cells) that affects your immune system by specifically targeting and blocking PD-L1. The PD-L1 pathway is involved in decreasing your body's natural immune response to fight cancer. By blocking PD-L1, avelumab may help your immune system stop, slow or reverse the growth of tumors. Avelumab has been approved by the Food and Drug Administration (FDA) for treatment of metastatic Merkel cell carcinoma, but it has not been approved for the treatment of neuroendocrine prostate cancer. Therefore, its use in this study is investigational. The word "investigational" means this is still being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA). This study will take place in 2 stages. If more than 1 subject in stage 1 shows a response to the study drug, then more subjects will be enrolled in stage 2.
Clinical trial: NCT03179410
Section: Voluntary Participation
Subsections: Statement Of Consent

"The purpose of this study, procedures to be followed, risks and benefits have been explained to me. I have been allowed to ask questions, and my questions have been answered to my satisfaction. I have been told whom to contact if I have questions, to discuss problems, concerns, or suggestions related to the research, or to obtain information or offer input about the research. I have read this consent form and agree to be in this study, with the understanding that I may withdraw at any time. I have been told that I will be given a signed and dated copy of this consent form." __________________________________________ ___________ ____________  
  
  
 Signature of Subject Date Time  
__________________________________________ ___________ ____________  
 Signature of Person Obtaining Consent Date Time  
DUHS IRB IRB NUMBER: Pro00080869
Clinical trial: NCT03179410
Section: Withdrawal from Study
Subsections: What About My Rights To Decline Participation Or Withdraw From The Study?

You may choose not to be in the study, or, if you agree to be in the study, you may withdraw from the study at any time. If you withdraw from the study, no new data about you will be collected for study purposes unless the data concern an adverse event (a bad effect) related to the study. If such an adverse event occurs, we may need to review your entire medical record. If your research blood sample has not already been processed for data collection, you may request that it be destroyed. Please note that it may not be possible to destroy samples, information and data created from your samples that may have already been used in research studies prior to your request. Your samples and/or data may be stored and shared for future research without additional informed consent if identifiable private information, such as your name and medical record number, are removed. If your identifying information is removed from your samples or data, we will no longer be able to identify and destroy them.  P NeuroEndocrine Phenotype Prostate Cancer (PICK NEPC)
Investigator: Andrew Armstrong, MD, ScM
Your decision not to participate or to withdraw from the study will not involve any penalty or loss of benefits to which you are entitled, and will not affect your access to health care at Duke. If you do decide to withdraw, we ask that you contact Dr. Armstrong in writing and let him know that you are withdrawing from the study. His mailing address is . We will tell you about new information that may affect your health, welfare, or willingness to stay in this study. Your doctor may decide to take you off this study if your condition gets worse, if you have serious side effects, or if your study doctor determines that it is no longer in your best interest to continue. The sponsor or regulatory agencies may stop this study at anytime without your consent. If this occurs, you will be notified and your study doctor will discuss other options with you. Your study doctor may ask you to return for a checkup before you stop your study drug if he or she thinks that stopping the drug suddenly may harm you. He or she may also ask you to complete the tests that would ordinarily occur when a person completes the study. 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.