Clinical trial: NCT03258593
Section: Alternatives
Subsections: Alternative Approaches Or Treatments What Other Choices Do I Have If I Do Not Take Part In This Study?

You do not have to participate in this study to be treated for your cancer. Your doctor will discuss your treatment options with you. These may include:
Having your bladder removed Receive additional treatment (with other approved or standard therapies) without being in a research study Taking part in another study
Clinical trial: NCT03258593
Section: Confidentiality
Subsections: Protections Against Misuse Of Genetic Information|Confidentiality Protections Provided In This Study|Certificate Of Confidentiality|Privacy Act

This study involves genetic testing on samples. Some genetic information can help predict future health problems of you and your family and this information might be of interest to your employers or insurers. The Genetic Information Nondiscrimination Act (GINA) is a federal law that prohibits plans and health insurers from requesting genetic information or using genetic information. It also prohibits employment discrimination based on your health information. However, GINA does not address discrimination by companies that sell life insurance, disability insurance, or long-term care insurance. GINA also does not protect you against discrimination based on an already-diagnosed condition or disease that has a genetic component.

Will your medical information be kept private? We will do our best to make sure that the personal information in your medical record will be kept private. However, we cannot guarantee total privacy. Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
The NIH and other government agencies, like the Food and Drug Administration (FDA),
which are involved in keeping research safe for people.  
National Institutes of Health Intramural Institutional Review Board The study Sponsor Center for Cancer Research or their agent(s)
Qualified representatives from AstraZeneca, the pharmaceutical company who produces Durvalumab and qualified representatives from Sesen Biotherapeutics, the pharmaceutical company who produces Vicineum The researchers conducting this study and the NIH follow applicable laws and policies to keep your identifying information private to the extent possible. However, there is always a chance that, despite our best efforts, your identity and/or information about your participation in this research may be inadvertently released or improperly accessed by unauthorized persons. In most cases, the NIH will not release any identifiable information collected about you without your written permission. However, your information may be shared as described in the section of this document on sharing of specimens and data, and as further outlined in the following sections. Further, the information collected for this study is protected by NIH under a Certificate of Confidentiality and the Privacy Act.

To help us protect your privacy, the NIH Intramural Program has received a Certificate of Confidentiality (Certificate). With this certificate, researchers may not release or use data or information about you except in certain circumstances. NIH researchers must not share information that may identify you in any federal, state, or local civil, criminal, administrative, legislative, or other proceedings, for example, if requested by a court. The Certificate does not protect your information when it:
1. is disclosed to people connected with the research, for example, information may be used for auditing or program evaluation internally by the NIH; or 2. is required to be disclosed by Federal, State, or local laws, for example, when information must be disclosed to meet the legal requirements of the federal Food and Drug Administration (FDA);
3. is for other research; 4. is disclosed with your consent.  
The Certificate does not prevent you from voluntarily releasing information about yourself or your involvement in this research. The Certificate will not be used to prevent disclosure to state or local authorities of harm to self or others including, for example, child abuse and neglect, and by signing below you consent to those disclosures. Other permissions for release may be made by signing NIH forms, such as the Notice and Acknowledgement of Information Practices consent.

The Federal Privacy Act generally protects the confidentiality of your NIH medical records we collect under the authority of the Public Health Service Act. In some cases, the Privacy Act protections differ from the Certificate of Confidentiality. For example, sometimes the Privacy Act allows release of information from your medical record without your permission, for example, if it is requested by Congress. Information may also be released for certain research purposes with due consideration and protection, to those engaged by the agency for research purposes, to certain federal and state agencies, for HIV partner notification, for infectious disease or abuse or neglect reporting, to tumor registries, for quality assessment and medical audits, or when the NIH is involved in a lawsuit. However, NIH will only release information from your medical record if it is permitted by both the Certificate of Confidentiality and the Privacy Act.
Clinical trial: NCT03258593
Section: Duration of Study Involvement
Subsections: During The Study|How Long Will I Be In This Study?

Once it has been determined that you are eligible and agree to participate in the study, you will have additional blood (about 2 tablespoons) and urine tests and you will be asked again about any medications you have been taking. A sample of your tumor will be tested to measure the amount of protein called EpCAM on the surface of the cancer cells. You may also need to have some of the tests that were done at screening repeated depending on how much time has passed. Your study team will let you know if any of the above tests need to be repeated. All participants in this study will receive Durvalumab and Vicineum. Vicineum will be administered using a Foley catheter placed in the bladder. You will hold the Vicineum for two hours and will have to change position every 15 minutes while sitting or lying in bed. After the two hours, the nurse will drain the Vicineum from your bladder. Durvalumab is an infusion administered approximately over 1 hour by placing an IV or using a peripherally inserted central catheter (PICC) placed in your arm. If you are not able to continue to take one of the study drugs for any reason (such as for side effects), the study treatment with both drugs will be stopped. Treatments are given in two phases. The first phase is called the Induction Phase. In the Induction Phase, you will receive Durvalumab every 4 weeks and Vicineum once a week for 3 months. After the Induction Phase, if you have no evidence of cancer or if you have a less aggressive form of cancer, you will continue to the Maintenance Phase. In the Maintenance Phase, you will receive Durvalumab every 4 weeks and Vicineum once every other week. During the treatment, you will see the doctor periodically to have many of the same tests done as were done in screening to see how you are doing - these include a physical exam and vital signs, blood samples (such as to check blood counts and organ function), and urine tests. You will also have an electrocardiogram (ECG or EKG) repeated at week 2 to check your heart function. An  
  
additional sample of your tumor will be obtained every 3 months and a CT every year to determine whether your tumor has returned. The research nurse will go over with you a study calendar that shows how often these tests, drug administration, and/or procedures will be done.

You will receive treatment for a total of 2 years as long as you are tolerating treatment and your cancer does not return. While on treatment, if your bladder cancer hasn't returned, you will continue to be evaluated every 3 months. If your bladder cancer returns, your doctor will discuss your treatment options.
Clinical trial: NCT03258593
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation|Risks From Blood Collection|Risks From Bladder Procedures|Privacy Risks Associated With Genetic Testing|Psychological Or Social Risks Associated With Return Of Incidental Or Secondary Findings|Radiation Risk|Ct Contrast Risks|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

What side effects or risks can I expect **from being in this study?** Durvalumab The following are side effects observed in patients receiving Durvalumab alone: Very Common Diarrhea Rash/itchy skin Abdominal pain Cough with or without mucus Fever Low thyroid function (hypothyroidism) which may cause fatigue, increased sensitivity to cold, constipation, dry skin, unexplained weight gain, puffy face, muscle weakness, slow heart rate, thinning hair, impaired memory.  
Upper respiratory tract infections

The risks from drawing blood may include discomfort from insertion of the needle, bruising, pain, redness or swelling at site of blood drawing, fainting and rarely, infection at the site of blood drawing.

Cystoscopy, TURBT, biopsies and catheterization may cause the following discomforts: burning when passing urine, blood-tinged urine, bladder infection or the need to urinate frequently following the procedures. The insertion of a catheter into the bladder through the urethra may be uncomfortable. You may be provided a local anesthetic (pain reliever put on your skin around where the catheter goes in) and sterile lubricant (jelly that makes the catheter easier to put in) at the time of the catheter placement. There is also a small risk that these procedures, particularly cystoscopy, TURBT and biopsies, could damage the lining of the bladder or cause a small hole in your bladder. This could lead to urine or drugs leaking out of the bladder causing severe side effects.  
PATIENT IDENTIFICATION **Consent to Participate in a Clinical Research Study**  
NIH-2977 (4-17) File in Section 4: Protocol Consent (1) Version Date: 01/10/2023 Page 9 of 17  
CC ICF template v. 09.27.19

It may be possible that genetic information from you could be used by law enforcement agencies or other entities to identify you or your blood relatives.

As part of the research study, it is possible that you could learn that you have genetic risks for another disease or disability. This may be upsetting and, depending on what you learn, might create a need to make challenging decisions about how to respond. Although your genomic information is unique to you, you share some genomic similarities with your children, parents, brothers, sisters, and other blood relatives. Therefore, learning your research results could mean something about your family members and might cause you or your family distress. Before joining the study, it may be beneficial to talk with your family members about whether and how they want you to share your results with them.

During your participation in this research study, you will be exposed to radiation from CT scans. The amount of radiation exposure you will receive from these procedures is equal to approximately 1.4 rem. A rem is a unit of absorbed radiation. Every day, people are exposed to low levels of radiation that come from the sun and the environment around them. The average person in the United States receives a radiation exposure of 0.3 rem per year from these sources. This type of radiation is called "background radiation."
No one knows for sure whether exposure to these low amounts of radiation is harmful to your body. The CTs that you get in this study will expose you to the roughly the same amount of radiation as 4.7 years' worth of background radiation. Most of the time, this amount of extra radiation is not harmful to you. However, scientists believe that being exposed to too much radiation can cause harmful side effects. This could include getting a new cancer. We estimate that this could happen in about 1 out of every 1000 people who get a very large amount of extra radiation.

Itching, hives or headaches are possible risks associated with contrast agents that may be used during CT imaging. Symptoms of a more serious allergic reaction include shortness of breath and swelling of the throat or other parts of the body. Very rarely, the contrast agents used in CT can cause kidney problems for certain participants, such as those with impaired kidney function.  
PATIENT IDENTIFICATION **Consent to Participate in a Clinical Research Study**
NIH-2977 (4-17) File in Section 4: Protocol Consent (1) Version Date: 01/10/2023 Page 10 of 17 CC ICF template v. 09.27.19

You may or may not receive direct medical benefit from participating in this study. Even if treatment with Durvalumab and Vicineum demonstrates some efficacy such that some participants in this study are able to delay or avoid having their bladder removed, such a benefit cannot be guaranteed for all participants in the study. The possible benefit to other people with this condition includes learning more information about treatment in participants with bladder cancer that has not spread to the muscle in the bladder.
Clinical trial: NCT03258593
Section: Procedures
Subsections: Description Of Research Study What Will Happen If You Take Part In This Research Study? Before You Begin The Study|Research Tests

You will need to have some exams, tests and procedures to find out if you can be in the study. These exams, tests and procedures are usually a part of regular cancer care and may be done even if you do not join the study. However, there are some extra exams, tests and procedures that you will need to have if you take part in this study. Most of these tests will be done under a separate protocol for screening or records will be collected if you had these performed for another reason (such as standard of care or outside of the NIH).If you have had some of them recently, they may not need to be repeated.

In addition to the tests that we will conduct to determine whether you are having side effects or if you are responding to the study therapy, we will also collect samples from you for purposes of research only. These studies include:  
Urine: before you have received any study drug, first void after you have received your week 1 dose of Vicineum; first void the next morning after week 1 Vicineum; day 7 void prior to start of week 2 Vicineum; week 6, week 10, and week 13 before study therapy; 3 months; and 6 months.  
Blood: Research tests will be done on blood taken at various times (before you have received any study drug, at 2 weeks, 3 weeks, 5 weeks, 8 weeks, 3 months, 6 months) during your participation in this study. The NIH has set a limit on the maximum amount of blood that can be taken for research. This limit is based on your age. For adults, no more than 37 tablespoons can be taken over an 8-week period.  
Tumor biopsies: Any biopsies done on this study will be for clinical reasons to rule out tumor recurrence, however, extra biopsy material (if available) will be used for research purposes.  
Genetic testing: We will use your tissue sample to compare gene expression profiles in tumor cells before and after treatment with Vicineum and Durvalumab. This will help us better understand how the study drugs work inside the human body.
Additional research testing: Tumor and blood samples collected for research purposes on this study may be used to look for specific changes in the DNA in tumors that could be used to develop new ways of diagnosing and treating cancer. DNA (also called deoxyribonucleic acid) in the cells carries genetic information and passes it from one generation of cells to the next - like an instruction manual. While normal tissue contains the DNA (instructions) that you were born with, DNA in tumor cells has changed - or mutated - and we think that change in the DNA is what causes tumors to form and to grow. RNA (also called ribonucleic acid) carries the instructions from the DNA to the parts of your cells that make proteins.  
To look at your DNA and RNA, we may use do what is called "DNA or RNA sequencing." This is where we will do special tests in the lab to look at the sequence, or order, of how your DNA or RNA are put together. This is what makes you unique. To determine which parts of the DNA or RNA have mutated, we will compare the DNA or RNA in your tumor cells to DNA or RNA from normal cells. We will then analyze the results from similar tumors to see if there are any changes in the DNA or RNA that are common to a particular type of tumor. To examine the tumor and normal tissue we may use several different techniques depending on the type of tissue we collect. These could include growing cell lines (cells which keep dividing and growing in the laboratory, sometimes for years allowing us to continually study those cells), xenograft studies (placing or growing cells in another animal, such as mice), and looking in detail at the parts of the genes that produce specific proteins. However, you should know that the analyses that we perform in our laboratory are for research purposes only; they may not be as accurate as the tests that are performed in a laboratory that is certified to perform genetic testing or testing for routine clinical care. For these reasons, we will not give you the results of the research tests done on your research samples in most cases. There may be exceptions to what we share with you, and this is described later in this consent form in the section for "Return of research results".
Clinical trial: NCT03258593
Section: Purpose of Research
Subsections: Why Are You Being Asked To Take Part In This Study?

You are being invited to participate in a research study because you have been diagnosed with bladder cancer and your cancer has not spread to the muscle in the bladder. Your cancer may be spreading on the lining of the bladder (this is called carcinoma in situ [CIS]) and/or may look like a polyp (papillary disease). In the past, you were treated with BCG, and either your bladder cancer did not respond to BCG treatment or your bladder cancer returned after your BCG treatment was completed. Currently, your bladder cancer is thought to be curable by having surgery to remove your bladder. By participating in this study, you agree to have treatments with Durvalumab in combination with Vicineum, an experimental therapy, rather than having surgery now to remove your bladder. You will be checked approximately every 3 months with a cystoscopy, by examining cells in the urine, and possibly bladder biopsies or bladder tumor resection while on treatment to see if your cancer seems to be getting better or worse. However, there is risk that by not having surgery to remove  
  
your bladder now, your bladder cancer could progress to the point where it is no longer curable by removing your bladder or from any other types of treatment.
Clinical trial: NCT03258593
Section: Voluntary Participation
Subsections: It Is Your Choice To Take Part In The Study

You may choose not to take part in this study for any reason. If you join this study, you may change your mind and stop participating in the study at any time and for any reason. In either case, you will not lose any benefits to which you are otherwise entitled. However, to be seen at the NIH, you must be taking part in a study or are being considered for a study. If you do choose to leave the study, please inform your study team to ensure a safe withdrawal from the research.  
The purpose of this research study is to obtain information on the safety and effectiveness of combination treatment with Durvalumab and Vicineum when given to participants with bladder cancer that has not spread to the muscle in the bladder. If you join this research study, you will receive an investigational drug Vicineum. Investigational means that it has not been approved by the U.S. Food and Drug Administration (FDA) for treatment of your cancer. Vicineum is a drug made of an antibody connected to a protein that can kill cells. This protein is a modified "pseudomonas exotoxin A." Vicineum is designed to attach to cells that have a different protein called EpCAM on the outside of the cell. After attaching to a cell, the modified pseudomonas exotoxin A can be released inside the cell causing the cell to die. It is thought that almost all bladder cancer cells have EpCAM on the surface of their cells. Durvalumab is a drug designed to boost the body's immune system by targeting a protein on tumor cells called PDL-1. PDL-1 normally maintains the balance of the immune system. In cancer, PDL1 helps tumors evade detection and elimination by the immune system. Durvalumab may increase the immune system's ability to identify and destroy cancer cells. Durvalumab, was recently approved by the FDA for metastatic urothelial/bladder cancer. Although it was FDA approved at a different dose than what is administered in this trial, there is safety data from several trials for the dosage used in this protocol. There is some evidence in a mouse model that the combination of these two drugs can be more effective in shrinking your tumor. Therefore, we are evaluating both the safety of the combination as well as how well the combination works. As of February 2021, Durvalumab is no longer approved in the US for metastatic urothelial/bladder cancer who have had their disease worsen on chemotherapy. This decision was made between the manufacturer of this drug and the FDA and was not based on any safety issues. Durvalumab is considered investigational and the FDA has given us permission to use it in this study. Early results from the current study provide data to support the continuation of this trial.
Clinical trial: NCT03258593
Section: Withdrawal from Study
Subsections: Stopping Therapy

Your doctor may decide to stop your therapy for the following reasons:
if he/she believes that it is in your best interest if your disease comes back during treatment if your health status changes during the study such that receiving therapy might be too dangerous if you become pregnant if you have side effects from the treatment that your doctor thinks are too severe if new information shows that another treatment would be better for you if you are unable to follow the study requirements if the study is ended In this case, you will be informed of the reason therapy is being stopped. You can stop taking part in the study at any time. 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.