Clinical trial: NCT02015104
Section: Alternatives
Subsections: Alternative Approaches Or Treatments What Are My Other Choices If I Do Not Take Part In This Study?

If you decide not to take part in this study, you have other choices. For example:
x you may choose to have the usual approach described above, i.e., multiple courses of BCG therapy x if you fail a second induction course, you may have radical cystectomy with pelvic lymphadenectomy, although it is a major surgery and carries a small, but real, mortality rate x you may choose to take part in a different study, if one is available x or you could decide not to be treated
Clinical trial: NCT02015104
Section: Confidentiality
Subsections: Who Will See My Medical Information?|Certificate Of Confidentiality

Your privacy is very important to us and the researchers will make every effort to protect it.  
Your information may be given out if required by law. For example, certain states require doctors to report to health boards if they find a disease like tuberculosis. However, the researchers will do their best to make sure that any information that is released will not identify you. Some of your health information, and/or information about your specimen, from this study will be kept in a central database for research. Your name or contact information will not be put in the database. There are organizations that may inspect your records. These organizations are required to make sure your information is kept private, unless required by law to provide information. Some of these organizations are:  
x The study sponsor and any drug company supporting the study.  
x The Institutional Review Board, IRB, is a group of people who review the research with the goal of protecting the people who take part in the study.  
x The Food and Drug Administration and the National Cancer Institute in the U.S., and similar ones if other countries are involved in the study.

To help us protect your privacy, we have obtained a Certificate of Confidentiality. The researchers can use this Certificate to legally refuse to disclose information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if there is a court subpoena. The researchers will use the Certificate to resist any demands for information that would identify you, except as explained below. There are several circumstances in which the Certificate does not provide coverage. These include when information:
x will be used for auditing or program evaluation internally by the NIH; or  
PATIENT IDENTIFICATION **CONTINUATION SHEET for either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84) P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
STUDY NUMBER: 15-C-0087 CONTINUATION: page 12 of 15 pages  
x must be disclosed to meet the legal requirements of the federal Food and Drug Administration (FDA).  
x is necessary for your medical treatment and you have consented to this disclosure; x is for other research.
In addition, identifiable, sensitive information protected by this Certificate cannot be accepted as evidence or used for any purpose in any action, suit, or proceeding without your consent. You should understand that a Certificate of Confidentiality does not prevent you or a member of your family from voluntarily releasing information about yourself or your involvement in this research. If an insurer, employer, or other person obtains your written consent to receive research information, then the researchers will not use the Certificate to withhold that information.  
The Certificate of Confidentiality will not protect against the required reporting by hospital staff of information on suspected child abuse, reportable communicable diseases, and/or possible threat of harm to self or others.
Clinical trial: NCT02015104
Section: Duration of Study Involvement
Subsections: How Long Will I Be In This Study?

You will receive the study drugs for up to 15 weeks, depending on which group you are in. After you finish the study drugs, your doctor will continue to watch you for side effects until you undergo another bladder scope/biopsy. Afterwards, your condition will be followed using standard-of-care surveillance for this type of bladder cancer for one year.
Clinical trial: NCT02015104
Section: Participant's Rights
Subsections: Research Subject'S Rights What Are My Rights In This Study?

Taking part in this study is your choice. No matter what decision you make, and even if your decision changes, there will be no penalty to you. You will not lose medical care or any legal rights.
Clinical trial: NCT02015104
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation|Study Group 1 And Study Group 2 - Possible Side Effects Of Bcg Vaccine: Possible Side Effects Of Bcg Common, Some May Be Serious|Possible Side Effects Of Panvactm|Possible, Some May Be Serious Reported But Undetermined: Rash|Potential Benefits Of Participation What Possible Benefits Can I Expect From Taking Part In This Study?

What possible risks can I expect from taking part in this study? If you choose to take part in this study, there is a risk that you may:
x Lose time at work or home and spend more time in the hospital or doctor's office than usual x Be asked sensitive or private questions which you normally do not discuss The vaccines used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. The study doctor will be testing your blood and will let you know if changes occur that may affect your health. There is also a risk that you could have side effects. Here are important points about side effects:  
x The study doctors do not know who will or will not have side effects. x Some side effects may go away soon, some may last a long time, or some may never go away.  
x Some side effects may interfere with your ability to have children.  
  
  
STUDY NUMBER: 15-C-0087 CONTINUATION: page 5 of 15 pages x Some side effects may be serious and may even result in death.  
Here are important points about how you and the study doctor can make side effects less of a problem:  
x Tell the study doctor if you notice or feel anything different so they can see if you are having a side effect.  
x The study doctor may be able to treat some side effects.  
x The study doctor may adjust the study drugs to try to reduce side effects.
The tables below show the most common and the most serious side effects that researchers know about. There might be other side effects that researchers do not yet know about. If important new side effects are found, the study doctor will discuss these with you.

In 100 people receiving BCG, more than 10 may have:  
x Fever x Chills x Malaise  
x Flu-like symptoms  
x Increased fatigue. x Visible blood in urine x Irritative voiding symptoms  
x Urinary tract infection  
PATIENT IDENTIFICATION **CONTINUATION SHEET for either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84) P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
  
  
  
STUDY NUMBER: 15-C-0087 CONTINUATION: page 6 of 15 pages Study Group 2 - In addition to side effects outlined above, people who are in Group 2 may also experience the possible side effects of PANVACTM **listed below:**

Vaccinia (Priming Vaccination) Many of the potential side effects from the vaccination are related to allergic responses to vaccinia or to an abnormal immune system. If you previously have had a smallpox (vaccinia) vaccination, you must have never had an allergic or severe reaction to such a vaccination. Because you may "shed" live virus through your lesion for several days after vaccination, you must be able to avoid close contact with certain individuals for at least two weeks after each vaccination. These individuals include children under 3 years of age; women who are pregnant or breast-feeding; individuals with active or a history of eczema or other eczematoid skin disorders such as active cases of extensive psoriasis, exfoliative skin diseases, severe rashes, generalized itching, infections, burns, chicken pox, or skin trauma; and/or immune suppressed individuals such as individuals with leukemia or lymphoma, with AIDS or HIV positive blood test, or those receiving immunosuppressive treatment. "Close contact" means that these people share your house, you have repeated bodily contact with them, and/or you take care of them and touch them with your hands. You must not start treatment if you have any healing scars or skin rashes (for example, a burn or poison ivy), until the skin condition has healed. If you have any questions about this list of precautions or any of these medical terms and diagnoses, you should ask about them before starting treatment. It is very important that you tell us if you have any concerns about these precautions for your own safety and the safety of those you may come in contact with. On average, vaccinia stays active in your body for approximately 13-14 days. Therefore, prior to receiving your next vaccine, you will be evaluated for evidence of pyoderma, vesicles (lesions seen on your skin at or around your vaccine site), or evidence of persistent vaccinia infection.  
Physical evidence of persistent viral replication (which would be evidenced by the skin lesions, swelling of lymph nodes, and or fever) would require an evaluation prior to next vaccine administration that might include a skin or lymph node biopsy and may delay the next vaccine. Side effects from the vaccinia vaccine are most common in young children, patients with disorders of the immune system, and individuals with skin disorders. That is why precautions are taken to exclude such individuals from exposure. It is important that you not touch the vaccination site and then touch other parts of your body. This is because the vaccinia virus may be transferred to other sites including the eye, the mucus membrane of the nose or mouth, or other area by rubbing the vaccination site and subsequently rubbing the eye or an open skin area. Spreading the virus in this way is known as autoinoculation. Healing usually occurs in 5-7 days. Blindness can result if vaccinia gets into the eye. A dressing will be placed over the vaccination site to reduce this risk.  
  
STUDY NUMBER: 15-C-0087 CONTINUATION: page 7 of 15 pages

Other possible side effects associated with the vaccinia virus used to make the PANVAC-V vaccine:
x Caution is advised as touching the vaccination site can cause accidental spread of the live virus to other parts of your body or to other people.  
x Serious side effects can occur if the virus is spread to your eyes (including blindness). x Swelling of the heart which may cause chest pain or shortness of breath.  
x Severe skin rash with or without blisters that can involve the inside of your mouth and other parts of the body and may be wide-spread. Areas of the skin that have or previously had eczema can also be affected.  
x Skin lesions and blisters on the skin can develop and not heal properly. When this happens, the virus can cause damage to large areas of your skin and tissue and cause damage to your bones and organs. This condition can become severe and cause death.  
x Anemia which may require blood transfusion x Diarrhea, nausea, vomiting x Pain x Chills, tiredness, fever x Flu-like symptoms including body aches x Swelling and redness at the site of the medication injection x Loss of appetite x Muscle weakness x Headache, fainting x Cough x Increased sweating x Itching, skin changes  
  
  
  
STUDY NUMBER: 15-C-0087 CONTINUATION: page 8 of 15 pages  
x Confusion and headache.  
x Serious adverse events or death can occur if the virus is spread to young children, women who are pregnant, individuals with a weakened immune system, or individuals with certain types of skin disorders.  
x Infection or death of fetus if you are or become pregnant or accidentally spread the live virus to another woman who is pregnant.
Let your study doctor know of any questions you have about possible side effects. You can ask the study doctor questions about side effects at any time.

This study may or may not help you but researchers should learn if it can improve your survival by six months or more compared to the usual survival of about two years with the usual approach. This study may help researchers learn things that may help people in the future.  
PATIENT IDENTIFICATION **CONTINUATION SHEET for either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84) P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
  
  
STUDY NUMBER: 15-C-0087 CONTINUATION: page 9 of 15 pages
Clinical trial: NCT02015104
Section: Procedures
Subsections: Description Of Research Study What Are The Study Groups?|What Extra Tests And Procedures Will I Have If I Take Part In This Study?

This study has two study groups.  
x Group 1 will get the usual BCG therapy used for this type of cancer. x Group 2 will get the usual BCG therapy used for this type of cancer plus a study drug called the PANVAC™ vaccine. The PANVAC™ vaccine consists of two steps, the initial priming followed by the boost. The vaccinia priming vaccine is administered on week 0, and the fowlpox boosting vaccine is administered on weeks 3, 7, 11 and 15.
A computer will randomly put you in a study group. This is done because no one knows if one study group is better, the same, or worse than the other. Once you are put in one group, you cannot switch to another group. Neither you nor your doctor can choose which group you will be in.  
PATIENT IDENTIFICATION **CONTINUATION SHEET for either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84) P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
  
STUDY NUMBER: 15-C-0087 CONTINUATION: page 3 of 15 pages

Most of the exams, tests, and procedures you will have are part of the usual approach for your cancer. However, there are some extra tests, and/or procedures that you will need to have if you take part in this study.
Clinical trial: NCT02015104
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

PANVAC™ is a poxvirus-based cancer vaccine that has been tested in a variety of cancers. Two proteins in particular are usually produced by many cancers and may be used as a target for your immune system to attack the cancer. The PANVAC™ vaccine places the genes for these two proteins inside a virus vaccine in order for your body to recognize these proteins as "foreign" invaders. If your immune system responds to this invasion, your tumor may become susceptible  
PATIENT IDENTIFICATION **CONSENT TO PARTICIPATE IN A CLINICAL RESEARCH STUDY**  
- Adult Patient or - Parent, for Minor Patient  
NIH-2514-1 (07-09) P.A.: 09-25-0099 File in Section 4: Protocol Consent (1)  
STUDY NUMBER: 15-C-0087 CONTINUATION: page 2 of 15 pages to your body's immune system. By using this vaccine, we are attempting to stimulate your body's immune system to recognize and destroy the tumor cells that produce two specific proteins. The purpose of this study is to compare the good and bad effects of using this poxvirus vaccine, PANVAC™ and the usual BCG therapy to using the standard BCG therapy alone. For example, treatment with the PANVAC™ vaccine could shrink your cancer but it could also cause side effects. This study will allow the researchers to know whether this different approach is better, the same, or worse than the usual approach.
Clinical trial: NCT02015104
Section: Voluntary Participation
Subsections: Why Am I Being Asked To Take Part In This Study?

You are being asked to take part in this study because you have high grade non-muscle invasive bladder cancer and have had at least one unsuccessful induction course (which means you still have cancer present after at least one 6-week course) of bacillus Calmette-Guerin (BCG) immunotherapy.
Clinical trial: NCT02015104
Section: Withdrawal from Study
Subsections: Can I Stop Taking Part In This Study?

Yes. You can decide to stop at any time. If you decide to stop for any reason, it is important to let the study doctor know as soon as possible so you can stop safely. If you stop, you can decide whether or not to let the study doctor continue to provide your medical information to the organization running the study. The study doctor will tell you about new information or changes in the study that may affect your health or your willingness to continue in the study.  
Even though it probably won't happen, it is possible that the manufacturer may not continue to provide the PANVACTM to the NCI for some reason. If this would occur, other possible options are:
x You might be able to get the PANVACTM from the manufacturer or your pharmacy but you or your insurance company may have to pay for it.  
x If there is no PANVACTM available at all, no one will be able to get more and the study would close.
If a problem with getting BCG and/or PANVACTM occurs, your study doctor will talk to you about these options. The study doctor may take you out of the study:  
x If your health changes and the study is no longer in your best interest x If new information becomes available x If you do not follow the instructions given to you by the study doctor x If the study is stopped by the sponsor x if your disease comes back during treatment x if you have side effects from the treatment that your doctor thinks are too severe  
PATIENT IDENTIFICATION **CONTINUATION SHEET for either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84) P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
  
STUDY NUMBER: 15-C-0087 CONTINUATION: page 10 of 15 pages x if new information shows that another treatment would be better for you In this case, you will be informed of the reason therapy is being stopped. However, if you decide to stop taking part in the study, we would like you to talk to the study doctor and your regular doctor first. If you decide at any time to withdraw your consent to participate in the trial, we will not collect any additional medical information about you. However, according to FDA guidelines, information collected on you up to that point may still be provided to the sponsor or designated representatives. If you withdraw your consent and leave the trial, any samples of yours that have been obtained for the study and stored at the NCI can be destroyed upon request. However, any samples and data generated from the samples that have already been distributed to other researchers or placed in the research databases cannot be recalled and destroyed.