Clinical trial: NCT00972309
Section: Alternatives
Subsections: Alternative Approaches Or Treatment

Treatment options for patients with elevated PSA levels but no evidence of disease spread to other organs following primary treatment for their prostate cancer includes watchful waiting or androgen deprivation hormone therapy. However it is unclear for patients with this stage of disease (Stage D0) what is the best approach. Because many patients prefer to avoid the side effects of hormonal treatment (impotence, hot flashes, loss of libido, breast tenderness, osteoporosis and bone fractures) watchful waiting is often chosen.  
If you develop evidence of disease progression, involving spread of your prostate cancer to the bone, brain or other organs, alternative treatments/therapy for your cancer may include:
➢ Treatment with hormone therapy, radiotherapy, chemotherapy or a combination of these approaches.  
➢ Supportive care (treatment designed only to help with symptoms from your cancer such as pain medication) ➢ Experimental treatments such as other types of immune therapy or investigational chemotherapy
➢ No further therapy at all Each of these alternative therapies has a unique set of benefits and risks. Your physician will discuss these options with you. Furthermore, other centers are performing clinical trials with investigational agents including immune-based therapies and vaccines as well as standard chemotherapy that you may want to consider as an alternative to this proposed trial.  
STUDY NUMBER: 09-C-0139 CONTINUATION: page 8 of 11 pages The decision not to participate in this study will not compromise your eligibility for other studies in the future. If you choose not to participate in the study, you will be referred back to your regular physician for medical care.
Clinical trial: NCT00972309
Section: Participant Responsibilities
Subsections: What Will I Need To Do Before I Begin The Study?

You will need to have the screening examinations, tests or procedures to find out if you can be in the study. Some of these examinations, test or procedures may be repeated during the study to assure your safety and to assess your response to TARP peptide vaccination. Some of these screening tests may also be performed at your outside home institution. During your initial visit to the clinical center you will complete the "screening process". You will be under the care of a specialist in internal medicine, oncology and/or immunology. The examinations, tests, and procedures are a part of the screening process and the results from these studies will determine your eligibility to participate in this study.  
You will be asked to take part in this research study if we determine from screening that:
➢ You have prostate cancer and an elevated or increasing PSA level following completion of primary treatment for your cancer.  
➢ You have no evidence that the prostate cancer has spread to other organs in your body.  
➢ You are not currently receiving androgen deprivation hormone therapy (prior therapy is allowed). ➢ You have a PSA doubling time (PSADT) between 3 and 15 months.  
➢ You screened positive for the immune system protein HLA-A*201 that binds TARP peptides. HLA is the major set of proteins that allows cells to be identified as self or non-self by the immune system.
Clinical trial: NCT00972309
Section: Participant's Rights
Subsections: Research Subject'S Rights

Participation in this research study is voluntary. You will get a copy of this Informed Consent and you may withdraw your consent to participate at any time. There are no penalties for leaving the study. Patients may ask our staff to answer any and all questions and we invite you to do so.  
Unexpected or unforeseeable side affects may also occur. Your participation in this protocol may be stopped without your consent if we find unacceptable side effects or feel that it would not be safe for you to continue. Any significant findings that relate to your treatment will be discussed with you.  
The Federal Privacy Act protects the confidentiality of your NIH medical records. However, you should know that the Act allows release of some information from your medical record without your permission. Organizations that may look at and /or copy your medical records for research, quality assurance, and data analysis include qualified representatives of the National Cancer Institute (NCI) and other government agencies such as the Food and Drug Administration (FDA).  
It is possible that the information obtained from your participation on this study may become valuable for commercial research and development purposes (included patentable inventions) that may be of significant benefit to society, the sponsor of this study, individual researchers, or third parties. The sponsor of this study is Dr. Jay A. Berzofsky. You will not receive direct financial benefit from such research and development. If information from this study is published in a medical journal, you will not be identified by name.  
STUDY NUMBER: 09-C-0139 CONTINUATION: page 10 of 11 pages The National Institutes of Health reviews NIH staff researchers at least yearly for conflicts of interest. The following link contains details of this process: http://ethics.od.nih.gov/forms/Protocol-Review-Guide.pdf. You may ask your research team for additional information or a copy of the Protocol Review Guide.  
If you refuse to participate, withdraw from the protocol or at the completion of the protocol, we will attempt to offer you participation in other NIH protocols if these are available. If there is no suitable research study you will be referred back to your home physician for further management. It is important that you understand and agree that participation in this protocol does not constitute a promise of long-term medical care here at the NIH Clinical Center.
Clinical trial: NCT00972309
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation|Potential Benefits Of Participation

The vaccines described in this study are experimental and whether the vaccines will induce an immune response and the side effects of the vaccine are not known. Everyone taking part in the study will be monitored very carefully for any side effects and we will ask you to fill out a Vaccine Report Card to monitor any symptoms you may have following your vaccine injection. Since we don't know all the side effects that may be associated with these vaccines, it is very important that you report any changes that you may notice, even if your study team does not specifically ask about them. Many side effects go away shortly after the study vaccine is stopped, but in some cases, side effects may be serious, long lasting, and may even cause death. You should talk to your study team about all side effects that you have while taking part in the study. It is important that you discuss any drugs (over-the-counter, prescription, illegal, or herbal) with your study team while you are participating in this study. Your time commitment to this study would involve visits to the NIH Clinical Center every three weeks for the vaccine administration, blood collection, and clinic visits that generally involve a two day stay. A total of five vaccines will be given. Individuals who have evidence that they have developed an immune response or PSA doubling time response to TARP peptide vaccination at 24 weeks will be eligible to receive a sixth dose of vaccine at Week 36. All patients will receive a booster dose of TARP vaccine at Weeks 48 and 96 and undergo repeat staging scans: CT scan (chest, abdomen, pelvis) and bone scan. Potential side affects associated with specific components of this research study are as follows:
- **Apheresis:** You may have some tingling in your face and lips due to the medicine used to keep your blood from clotting during the procedure. The nurses may give you calcium-containing tablets, such as TUMS, to chew that takes away this tingling. Some patients may feel faint or light-headed during or after this procedure. We ask that you make sure you have a good meal prior to coming to the apheresis lab to prevent this. Trained nurses will carry out all apheresis procedures.  
- FluMist Vaccine**(given intranasally):** This vaccine cannot be given to you if you are allergic to eggs or egg products. It is unlikely, but you could experience an allergic reaction to the vaccine including shortness of breath, wheezing, or difficulty breathing; swelling of the face, lips, tongue, or other parts of the body; skin rash, itching, or hives. Some people also experience symptoms consistent with a very mild cold such as runny nose or nasal congestion.  
- **TARP Peptide Vaccine (given subcutaneously or intradermally)** - The vaccine may produce some discomfort, such as redness, swelling and tenderness at the injection site. These are known as local injection site reactions. Fever, chills, rash and flu-like symptoms may also occur. All of these are temporary. You will be monitored closely during vaccine administration for any complications. It is possible that you could develop an immune response to the TARP peptide that will cause inflammation in your prostate gland. This may produce discomfort. We do not anticipate significant systemic or organ toxicities, but because this is an investigational agent it is possible that other risks not mentioned could occur. In generally, peptide vaccines given to cancer patients have been found to be safe and very well tolerated.  
STUDY NUMBER: 09-C-0139 CONTINUATION: page 9 of 11 pages
- **Risks of blood draws**: There is a risk of discomfort or pain, bleeding, as well as mild arm bruising and swelling in the area where the blood is drawn. Rarely, a clot or infection may occur at the site of the blood draw. Some people also become faint, dizzy, or light-headed during or immediately after the blood draw.  
- **Risks from X-rays and/or Scans**: As part of this study, you will have imaging scans. These tests are necessary to monitor your disease. As a result of participating in this study, you will be exposed to a moderate amount of radiation (approximately 6.5 cGy). This amount is more than you would receive from a year of natural exposure, which is approximately 0.16 cGy. This exposure may slightly increase your chances of developing cancer in the future. If you are especially concerned with radiation exposure or you have had a lot of x-rays already, you should discuss this with your study team.

Taking part in this study may or may not provide a direct benefit to you. It is unknown whether vaccination with TARP
peptides will stimulate an immune response by your body. If an immune response is stimulated, it is also unknown what kind of effect this immune response will have on the PSA doubling time (PSADT): it could increase your PSADT (desirable effect), decrease your PSADT (undesirable effect) or have no effect. If TARP peptide vaccination stimulates an immune response that increases your PSADT, it may help your body to fight your prostate cancer more effectively. Since this is an experimental therapy, no benefit can be promised. However, the information we obtain from both the laboratory studies and your response to vaccination may also allow us advance the understanding and treatment of cancer for future patients.
Clinical trial: NCT00972309
Section: Procedures
Subsections: Description Of Research Study Procedures What Will I Need Before Screening For The Study?|Apheresis:|Flumist™ Vaccination:

Information regarding your cancer will be requested from your local oncologist. You will need to sign a Medical release form so that your information (progress notes, pathology reports, tissue slides) can be forwarded to the NIH.  
You will have the **HLA –A*201** screening blood test drawn at your local lab or at NIH. Blood samples drawn at outside institutions will be sent to NIH for HLA typing. You will need to sign a separate HLA screening consent to have this done. The NIH department of Pathology will review your prostate cancer tissue biopsy (or slides) to confirm the diagnosis of prostate cancer.  
STUDY NUMBER: 09-C-0139 CONTINUATION: page 3 of 11 pages

The procedure for obtaining certain types of blood cells through apheresis is a very common procedure that is done routinely here in the Clinical Center with very few risks. Apheresis requires you to have a needle placed in your arm where the blood can be removed from you and circulated through a cell separator machine (a machine that divides whole blood into red cells, plasma (the serum part) and white cells (that includes lymphocytes and monocytes). The white blood cells are removed and the plasma and red cells are returned to you through another needle in your other arm. The procedure takes approximately 1 to 3 hours to complete. One of the purposes of this procedure is to allow the investigator to collect a sufficient amount of immune cells to measure the immune response to the vaccine. This testing will provide no benefit to you and is part of the experimental portion of this research study. Patients do not need to be hospitalized for the procedure. The apheresis procedure will be done at the Department of Transfusion Medicine (Blood Bank) in the NIH Clinical Center and is carried out by trained nurses supervised by Blood Bank physicians.

You will also be vaccinated with an approved, licensed influenza vaccine called FluMist™ that is given as a nasal mist. FluMist™ contains very weakened but still live flu virus strains: other flu vaccines given into the muscle contain killed flu virus strains. To reduce the risk of transmitting the weakened virus to other patients, it will be administered immediately prior to your leaving the Clinical Center after your first visit. Following FluMist™ vaccination, the body develops an immune response to the weakened viruses that are in the vaccine. This vaccination will let us know how well your  
STUDY NUMBER: 09-C-0139 CONTINUATION: page 4 of 11 pages immune system is working and whether it can respond to vaccines designed to stimulate responses in cells of the immune system called T lymphocytes or T cells. FluMist™ vaccination should also prevent you from getting the flu.
Clinical trial: NCT00972309
Section: Voluntary Participation
Subsections: ![5_Image_0.Png](5_Image_0.Png) Nih 2514-2, Minor Patient'S Assent To Participate In A Clinical Research Study

STUDY NUMBER: 09-C-0139 CONTINUATION: page 6 of 11 pages  
| Schedule study Events Weeks 60-144 Wk 60 Wk  Wk  Wk  Wk                                                   | Wk   | Wk   | Wk   |     |     |     |    |    |
|-----------------------------------------------------------------------------------------------------------|------|------|------|-----|-----|-----|----|----|
| 72                                                                                                        | 84   | 96   | 108  | 120 | 132 | 144 |    |    |
| HLA-A*0201 Testing Prior to Screening Informed Consent Medical History & ROS                              | X    | X    | X    | X   | X   | X   | X  | X  |
| Physical Examination                                                                                      | X    | X    | X    | X   | X   | X   | X  | X  |
| Performance Status                                                                                        | X    | X    | X    | X   | X   | X   | X  | X  |
| Height                                                                                                    | X    | X    | X    | X   | X   | X   | X  | X  |
| Weight                                                                                                    | X    | X    | X    | X   | X   | X   | X  | X  |
| Vital Signs                                                                                               | X    | X    | X    | X   | X   | X   | X  | X  |
| Apheresis                                                                                                 | X    |      |      |     |     |     |    |    |
| FluMist Flu Vaccine TARP Peptide Vaccine                                                                 | X    |      |      |     |     |     |    |    |
| Vaccine Report Card                                                                                       | X    |      |      |     |     |     |    |    |
| CBC/differential, plts                                                                                    | X    | X    | X    | X   | X   | X   | X  | X  |
| PT / PTT Acute Panel                                                                                      | X    | X    | X    | X   | X   | X   | X  | X  |
| Hepatic Panel                                                                                             | X    | X    | X    | X   | X   | X   | X  | X  |
| Mineral Panel                                                                                             | X    | X    | X    | X   | X   | X   | X  | X  |
| Lipid Panel                                                                                               | X    | X    |      |     |     |     |    |    |
| Amylase / Lipase                                                                                          | X    | X    |      |     |     |     |    |    |
| Vitamin D, 25 hydroxy PSA                                                                                 | X    | X    | X    | X   | X   | X   | X  | X  |
| PSADT Calculation                                                                                         | X    | X    | X    | X   | X   | X   | X  | X  |
| Serum Testosterone                                                                                        | X    | X    | X    | X   | X   | X   | X  | X  |
| Urinalysis                                                                                                | X    | X    |      |     |     |     |    |    |
| HIV Serology Hepatitis B Serology Hepatitis C Serology HTLV-1 Serology VDRL EKG CT Scan  Chest/Abd/Pelvis | X    | X    |      |     |     |     |    |    |
| Bone Scan                                                                                                 | X    | X    |      |     |     |     |    |    |
| Lymphocyte Subsets                                                                                        | X    | X    | X    |     |     |     |    |    |
| Anti-TARP Antibody                                                                                        | X    | X    | X    |     |     |     |    |    |
| NKT Cell Assessment Tetramer Staining                                                                     | X    | X    | X    | X   | X   | X   | X  |    |
| IFN- ELISPOT                                                                                             | X    | X    | X    | X   | X   | X   | X  |    |
| 51Cr CTL Assay#                                                                                           | X    | X    | X    | X   | X   | X   | X  |    |
| PBMCs for Storage                                                                                         | X    | X    | X    | X   | X   | X   | X  |    |
| Serum for Storage                                                                                         | X    | X    | X    | X   | X   | X   | X  |    |  
X*: Patients who are PSA doubling time or immunologic responders at Week 24 will be eligible to receive a 6th dose of TARP peptide vaccine at Week 36. All patients will receive a booster dose of TARP peptide vaccine at Week 48 and 96.  
STUDY NUMBER: 09-C-0139 CONTINUATION: page 7 of 11 pages