Clinical trial: NCT03912818
Section: Alternatives
Subsections: Alternatives

You do not have to be in this study to receive treatment for your variant histology bladder cancer.  
Possible alternative treatments and side effects of these treatments depend on the characteristics of your bladder cancer, but would include the standard treatments that are part of this study. The effectiveness and side effects of other treatments may be different for different people. Instead of taking part in this study, you may choose to:
Surgically remove the tumor. Receive radiation therapy, but not as part of this study. Receive treatment with other chemotherapy drugs, including the standard treatments that are part of this study, or others. The study team will discuss which might be effective to treat your cancer. There are numerous treatments that may or may not be suitable for the specifics of your cancer. Receive treatment with other drugs called targeted therapies, which recognize specific features of certain cancers, and focus the treatment effect on those cells. The study team will discuss with you whether any of these might be effective to treat your cancer. Receive surgery plus 1 or more of the above therapies. There are specific names for the order in which this type of treatment is given.  
o Neoadjuvant treatment, which means to receive chemotherapy and/or radiation therapy before surgery. Having one or both of these before surgery may help shrink the tumor, which may be easier to remove during the surgery.  
o Adjuvant treatment, which means having a surgery first, then receiving chemotherapy and/or radiation therapy. The goal of adjuvant treatment is to kill any cancer cells that may be left in your body after the surgery. Even if there is no visible sign of cancer cells, your physician may suggest adjuvant treatment to kill remaining microscopic cancer, as this lowers the risk that the cancer may come back or spread.  
Participate in another research study with a different study drug or procedure While your type of cancer is treatable with currently approved and available medications and procedure, another alternative is to receive only comfort care, also called "palliative care," like painkillers. These types of treatments do not treat your cancer (ie, "are not curative"), and only make you comfortable ("symptom relief;" pain reduction; reduce tiredness, help with appetite problems or other problems caused by cancer). If you think you might prefer comfort care, please discuss this with your family, friends, and doctor. NOTE: The Study Doctors do not recommend this decision for you at this time, although it is and will remain your decision.  
  
  
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Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer The Study Doctors will discuss with you the risks and benefits of these alternatives, including which other treatments might be suitable for you. If you decide that you do not wish to take part in this study and wish to pursue any of these, or other alternatives, this will not change your regular medical care or the other treatment choices in any way.
Clinical trial: NCT03912818
Section: Confidentiality
Subsections: Confidentiality|Authorization To Use Your Health Information For Research Purposes

The results of this research study may be presented at scientific or medical meetings or published in scientific journals. Your identity and/or your personal health information will not be disclosed except as authorized by you or as required by law. However, there is always some risk that even de-identified information might be re-identified. Your research records may be disclosed outside of Stanford, including in computer databases and by other electronic methods, but you will only be identified by your unique study identifier, and not your name. Information linking your study identifier to your name will be kept in a secure location at Stanford and access will be limited to the Study Doctor and authorized members of the Study Team. Patient information may be provided to Federal and other regulatory agencies as required. The US FDA, for example, may inspect research records and learn your identity if this study falls within its jurisdiction.  
Participant ID:  
  
  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer The purpose of this research study is to obtain data or information on the safety and effectiveness of durvalumab; the results will be provided to the company providing durvalumab (AstraZeneca/MedImmune); the Food and Drug Administration (FDA); and other federal and regulatory agencies as required.  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer

Because information about you and your health is personal and private, it generally cannot be used in this research study without your written authorization. If you sign this form, it will provide that authorization. The form is intended to inform you about how your health information will be used or disclosed in the study.  
Your information will only be used in accordance with this authorization form and the informed consent form and as required or allowed by law. Please read it carefully before signing it.
Clinical trial: NCT03912818
Section: Duration of Study Involvement
Subsections: Duration Of Study Involvement

It is planned that each participant will take part in this study for up to about 5 months.  
Participant ID:  
  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer Information about the end of your participation in the study is provided under "Withdrawal from the study."
Clinical trial: NCT03912818
Section: Participant Responsibilities
Subsections: Participant Responsibilities

As a participant, your responsibilities include:
- Follow the instructions of the Protocol Director and study team.  
- Be sure to tell the study team all of your present and past diseases, allergies and any drugs or medications you are taking. This is for your safety. Other drugs or medications includes all prescription drugs; over-the-counter (OTC) drugs; herbal preparations; and nutritional supplements. These may interact with the study drug durvalumab or the chemotherapy. If any other medical provider prescribes new medications for you while you are on this study, please contact the study team before taking the new medicine, or have that medical provider contact the study team before prescribing it to you. You should not take any new non-prescription medicine while you are on this study unless you first check with the study team.  
Ask questions as you think of them. Tell the Study Doctor or study team if you change your mind about staying in the study. Tell the Study Doctor or study team about any side effects, doctor visits, or hospitalizations that you may have. Tell the Study Doctor or study team if you believe you might be pregnant or gotten your partner pregnant.  
o Men must use a medically-approved method of birth control, preferably a barrier method, for the duration of the treatment period and for at least 6 months after the last injection of durvalumab.  
o **Women** must use a medically-approved method of birth control, preferably a barrier method, for the duration of the treatment period and for at least 3 months after the last injection of durvalumab.  
Keep your study appointments. If it is necessary to miss an appointment, please contact the Study Doctor or research study team to reschedule as soon as you know you will miss the appointment.
Clinical trial: NCT03912818
Section: Participant's Rights
Subsections: Participant'S Rights|Experimental Subject'S Bill Of Rights

You should not feel obligated to agree to participate. Your questions should be answered clearly and to your satisfaction. If you decide not to participate, tell the Protocol Director. You can also tell any other member of the study team. You will be told of any significant new information that is learned during the course of this research study, which might affect your condition or your willingness to continue participation in this study. After you hear about this information, you have the right to withdraw from the program. You will be told the results of tests that are part of your medical care, but you may not be told the results of the research tests, including any future research tests.

As a research participant you have the following rights. These rights include but are not limited to the participant's right to:
- Be informed of the nature and purpose of the experiment; - Be given an explanation of the procedures to be followed in the medical experiment, and any drug or device to be utilized;
- Be given a description of any attendant discomforts and risks reasonably expected; - Be given an explanation of any benefits to the subject reasonably to be expected, if applicable;
- Be given a disclosure of any appropriate alternatives, drugs or devices that might be advantageous to the subject, their relative risks and benefits;
- Be informed of the avenues of medical treatment, if any available to the subject after the experiment if complications should arise;
- Be given an opportunity to ask questions concerning the experiment or the procedures involved;
- Be instructed that consent to participate in the medical experiment may be withdrawn at any time and the subject may discontinue participation without prejudice;
- Be given a copy of the signed and dated consent form; and - Be given the opportunity to decide to consent or not to consent to a medical experiment without the intervention of any element of force, fraud, deceit, duress, coercion or undue influence on the subject's decision.  
  
  
  
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Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer May we contact you about future studies that may be of interest to you? ___Yes ___No Signing your name means you agree to be in this study and that you will receive a copy of this signed and dated consent form. _______________________________________________ Printed Name of Adult Participant _______________________________________________ ____________ Signature of Adult Participant Date
_______________________________________________ If needed: Printed Name of Legally Authorized Representative (LAR) _______________________________________________ ____________ Signature of LAR Date _______________________________________________ LAR's Authority to Act for Participant (eg, parent, guardian, or conservator) _______________________________________________ Printed Name of Person Obtaining Consent (POC) _______________________________________________ ____________ Signature of POC Date  
  
IRB Use Only  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer The following witness line is to be signed only if the consent is provided as a summary form and accompanied by a short-form foreign language informed consent document.
Clinical trial: NCT03912818
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Possible Risks, Discomforts, And Inconveniences|Possible Risks Associated With Durvalumab|Diarrhea|Common Side Effects (Affects Between 1 In 100 And 1 In 10 Patients Treated)|Uncommon Side Effects (Affects Between 1 In 1,000 And 1 In 100 Patients Treated)|Rare Side Effects (Affects Between 1 In 10,000 And 1 In 1,000 Patients Treated)|Possible Risks Associated With Surgery (Radical Cystectomy)|Occasional, Some May Be Serious|Possible Risks Associated With Gemcitabine, Cisplatin, And Pegfilgrastim Common, Some May Be Serious|Occasional, Some May Be Serious About 4 To 20 Out Of 100 People Receiving Gemcitabine, Cisplatin, And Pegfilgrastim May Have:|Rare, And Serious

There are risks, discomforts, and inconveniences associated with any research study. This section describes the reasonably foreseeable risks; discomforts; and inconveniences that you may experience. In addition, because this is a research study, there may be risks that are not yet known
("unforeseeable"), including a risk of death due to unknown risks. These deserve careful thought.  
You should talk with the Study Doctor if you have any questions. You must tell the Study Doctor or study team about all side effects that you have. If you are not honest about your side effects, it may not be safe for you to stay in the study. Your Study Doctor may give you medications to try to help lessen some of the side effects. All patients in the study will be monitored for side effects. If you experience serious problems, you may be asked to return to the study center for more tests. If you experience the following symptoms of an allergic reaction, contact the Study Doctor or the Study Team immediately.  
Allergic reaction, including rash, hives, or blisters; increased heart rate (a fast pulse or tachycardia); or abnormal or increased sweating Swelling of the face, mouth, lips, gums, tongue or neck Wheezing or difficulty breathing Dizziness and fainting

Most of the possible side effects seen with durvalumab are mild to moderate. However, some side effects can be very serious and life-threatening and may even result in death. Some side effects do not need treatment while others generally get better with treatment. You may need to delay doses of durvalumab to allow the side effects to get better. The most important possible side effects, which are listed below, may occur because of the way durvalumab works on the immune system and they have been seen in patients treated with durvalumab in clinical studies. Side effects like these have also been seen in clinical studies with other drugs that are very similar to durvalumab. Management of these side effects may require the administration of drugs such as steroids or other agents that can affect your immune system and reduce inflammation. It is very important to tell your study doctor right away if you have any of these symptoms.

Rash/dry itchy skin Liver problems: Increases in the blood level of substances called enzymes found within your liver cells may occur. The enzyme changes are unlikely to make you feel unwell. However, if these blood enzyme levels become very high, your study doctor may need to stop the study medication. You may develop inflammation of the liver called hepatitis, however this is uncommon. Signs and symptoms of this include yellowing of the skin or whites of the eyes, dark urine, severe nausea and vomiting, pain in the upper right side of your abdomen, skin itchiness, not feeling hungry and bleeding or bruising more easily than normal.  
In addition to the important possible risks described above, patients with different types of cancer who have been treated with durvalumab alone in clinical trials have very commonly (ie, more than 10% of patients) reported: feeling tired, nausea, vomiting, abdominal pain, accumulation of fluid causing swelling, upper respiratory tract infections, decreased appetite, shortness of breath, cough, pain in muscles and joints and, fever.

- Inflammation in the lungs (pneumonitis): Symptoms may include but are not limited to a new or worsening cough, shortness of breath possibly with fever. Tell your study doctor right away if you have any of these symptoms as it may need to be treated urgently.  
- Low thyroid (Hypothyroidism): This is when the thyroid gland produces less thyroid hormone than it should which causes the metabolism to run too slow. Symptoms may include but are not limited to fatigue, increased sensitivity to cold, constipation, dry skin, unexplained weight gain, puffy face, muscle weakness, slow heart rate, thinning hair, impaired memory. The condition can be treated with replacement thyroid hormone.  
- High thyroid (Hyperthyroidism): This is when the thyroid gland produces too much thyroid hormone. Symptoms include anxiety or nervousness, weight loss, frequent and loose bowel movements, breathlessness, feeling hot and possibly having heart palpitations. Depending on the severity of the symptoms treatment may include just monitoring the symptoms, treating the symptoms themselves and/or giving medicine to block the thyroid hormone.  
- Kidney problems: You may have an increase of creatinine levels in a blood test (creatinine is a protein marker that measures kidney function) but not have any symptoms or feel unwell. Uncommonly a patient may experience nephritis which is an inflammation of the kidneys that stops the kidneys from working properly.  
- Nervous system problems: Symptoms can include unusual weakness of legs, arms, or face, numbness or tingling in hands or feet. In rare situations there is the potential for the inflammation of the nervous system to be severe and cause damage to the nerve cells or breakdown in the communication between nerves and muscles. **Tell your study doctor** right away if you have problems swallowing, if you start to feel weak very quickly and you are having trouble breathing.  
- Infusion Related Reactions: Reactions may occur during or after the infusion of study medication. The reaction may cause fever or chills and a change in blood pressure or  
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer difficulty in breathing which might be serious. Tell your study doctor right away if you experience any of these symptoms even if it has been several days after the infusion has been completed.  
- Inflammation of the intestine (colitis). It may cause abdominal pain and diarrhea with or without blood. Fever may be present. It may require you to receive additional fluids. If left untreated, in rare occasions this may lead to a tear in the wall of the intestine which can be serious and life threatening. **Tell your study doctor right away if you have any** of these symptoms.  
- As well as the important possible risks described above patients with different types of cancer who have been treated with durvalumab in clinical trials have commonly (ie 1% to less than 10% of patients) reported: a hoarse voice, painful urination, night sweats, pneumonia, oral thrush, dental and oral soft tissue infection and, influenza.

- Inflammation of the pancreas (pancreatitis): Pancreatitis usually causes symptoms of persistent upper abdominal pain (sometimes made worse by eating and drinking), nausea, vomiting and general weakness. Pancreatitis usually settles with simple measures but it can be a serious condition and can be fatal. **You should immediately tell your study doctor if** you develop any unusual symptoms. You may get an increase of lipase and amylase levels in a blood test (related to the pancreas) but not have any symptoms or feel unwell. Lipase and amylase are enzymes or protein markers that measure the function of your pancreas. Uncommonly these increases may be associated with pancreatitis.  
- Allergic reactions: These can cause swelling of the face, lips and throat, breathing difficulties along with hives or nettle like rash. **You should immediately tell your study** doctor if you develop any of these symptoms.  
- Problems with your adrenal glands (Adrenal Insufficiency): May cause stomach pains, vomiting, muscle weakness and fatigue, depression, low blood pressure, weight loss, kidney problems, and changes in mood and personality. These complications may be permanent and may require hormone replacement.  
- Inflammation of the muscles or associated tissues, such as blood vessels that supply the muscles (Myositis/polymyositis). Symptoms can include muscle weakness andaches, tired feeling when standing or walking, muscle pain and soreness that does not resolve after a few weeks.

- Type 1 Diabetes mellitus which may cause increased blood glucose levels (called
'hyperglycemia'): Symptoms may include weight loss, increased urination, increased thirst, and increased hunger. Type 1 diabetes will require replacement of insulin through injection.  
Tell your study doctor right away if you have any of these symptoms.  
- Problems with the pituitary gland (hypopituitarism): Hypopituitarism refers to decreased output of hormones from the pituitary gland in the brain and may be caused by inflammation of the pituitary gland (hypophysitis). Symptoms may include headaches, thirstiness, and  
Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer trouble seeing or double vision, leakage of breast milk or irregular periods in women. These complications may be permanent and may require hormone replacement.  
- Inflammation of the heart muscle (myocarditis). Symptoms can include chest pain, rapid or abnormal heart beat, shortness of breath and swelling of your legs. Tell your study doctor right away if you experience any of these symptoms.  
- Blistering and break down of the skin, mouth, and other mucous membranes (called pemphigoid).  
As well as the important possible risks described above, patients with different types of cancer who have been treated with durvalumab in clinical trials have rarely (i.e. less than 0.1% of patients) reported: inflammation of the membrane surrounding the heart, growths of tiny collections of inflammatory cells in different parts of the body, inflammation of the middle layer of the eye and other events involving the eye (e.g. Inflammation of the cornea and optic nerves), inflammation of the brain or the membranes that cover the brain and spinal cord, hardening and tightening of the skin and connective tissues and loss of skin color, and hematological events (e.g., abnormal breakdown of the red blood cells and low levels of platelets), inflammation of the blood vessels and rheumatological events (inflammatory disorder causing muscle pain and stiffness and autoimmune arthritis).  
In addition to the possible risks identified in patients treated with durvalumab, other immunemediated side effects are possible that have not been observed, and can result in inflammatory side effects in any organ or tissue.

This type of surgery is commonly performed in your country for patients with muscle invasive bladder cancer. Your study doctor will explain the surgical procedure and possible side effect related to the surgical procedure. If you have any questions related to the surgery, your study doctor will be able to explain this in more detail.  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer Possible Risks Associated with Methotrexate, Vinblastine, Doxorubicin, Cisplatin, and Filgrastim (or Pegfilgrastim)
COMMON, SOME MAY BE SERIOUS
More than 20 out of 100 people receiving methotrexate, vinblastine, doxorubicin, cisplatin, and filgrastim (or pegfilgrastim) may have:
- Low number of red blood cells (anemia) - This can lead to shortness of breath, weakness, and fatigue.  
- Low number of platelets which help the blood clot - This can lead to unexplained bruising or bleeding.  
- Low number of white blood cells - This can make you more vulnerable to infection.  
- Hair loss
- Nausea
- Vomiting - Skin irritation at site of drug injection which can be severe
- Damage to kidneys
- Damage to hearing - Changes in urine color (doxorubicin may discolor your urine for up to 1-2 days but this is harmless)
- Soreness or painful ulcers of the mouth lasting a couple of days
- Sensitivity to the sun
- Blood measurements of kidney function (creatinine) and normal elements in the blood including blood sugar (glucose), potassium, magnesium, calcium, and sodium may become abnormal
- Electrolytes, which are normal elements measured in the blood, including potassium, magnesium, and sodium may become low and possibly require replacement
- Sores in mouth and/or throat
- Bone pain Page 23 of 40 Approval Date: February 9, 2022 Expiration Date: February 9, 2023
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Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer

About 4 to 20 out of 100 people receiving methotrexate, vinblastine, doxorubicin, cisplatin, and filgrastim (or pegfilgrastim) may have:
- Allergic reaction
- Upset bowels - this can lead to either constipation or diarrhea
- Loss of appetite
- Weight loss
- Strange taste - A metallic or bitter taste can occur during treatment. A flavored hard candy or mint will help to disguise this taste.  
- Flu-like symptoms (such as fever, aches, pains, and shivering) - Tingling and numbness in the fingers or toes - Ringing in the ears
- High frequency hearing loss - This can be permanent
- Skin and nail changes
- Rash or irritation at the injection site
- Weakness of the heart - This is uncommon and can happen with increasing doses of doxorubicin.  
RARE, AND SERIOUS
About 3 or fewer out of 100 people receiving methotrexate, vinblastine, doxorubicin, cisplatin, and filgrastim (or pegfilgrastim) may have:
- Sore eyes
- Depression - Headaches
- Jaw pain
- Seizure
- Cancer of the bone marrow caused by chemotherapy later in life.  
- Death - In rare cases, death can occur in patients with a severe allergic reaction to the chemotherapy or in patients who develop a life-threatening infection.  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer

More than 20 out of 100 people receiving gemcitabine, cisplatin, and pegfilgrastim may have:
- Low white blood cell counts (may make you more likely to get an infection)
- Low red blood cell counts (may make you feel tired or weak)
- Low platelet counts (may make you more likely to bruise or bleed)
- Nausea
- Vomiting
- Loss of appetite - Diarrhea - Fatigue - Blood measurements of kidney function (creatinine) and normal elements in the blood including blood sugar (glucose), potassium, magnesium, calcium, and sodium may become abnormal
- Lightheadedness - Headaches
- Changes in blood pressure
- Skin irritation at site of drug injection
- Damage to kidneys
- Damage to hearing
- Rash
- Flu-like illness with fever on day of chemotherapy - Electrolytes, which are normal elements measured in the blood, including potassium, magnesium, and sodium may become low and possibly require replacement
- Bone pain Page 25 of 40  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer

- Sores in mouth and/or throat
- Alterations in taste
- Allergic reaction (including flushing, skin rash, changes in blood pressure and/or difficulty breathing)
- Stomach cramps
- Hair loss
- Numbness in the hands and feet - Loss of blood supply to the intestines that may require surgery - Inflamed pancreas
- Dizziness and shooting back pain when bending your neck forward
- Confusion - Blurred vision or a sensation of flashing light
- Mood changes
- Liver damage and/or failure - Seizures
- Fainting
- Irregular heartbeat
- Heart attack
- Ringing in the ears
- High frequency hearing loss - This can be permanent

About 3 or **fewer out of 100 people receiving gemcitabine, cisplatin, and pegfilgrastim may**
have:
- Cancer of the bone marrow caused by chemotherapy later in life.  
- Seizure
Clinical trial: NCT03912818
Section: Procedures
Subsections: Procedures|Study Evaluation Procedures|Study Follow-Up Procedures Your Tissue / Data Samples For Research And Genetic Testing|Handling Of Your Tissue Samples

It may be harmful to enter this study while receiving some medications, therefore, you may need to stop taking certain medications. Your Study Doctor will review your medications and provide you with specific instructions. Before you join this study, Dr Srinivas and/or the research study team will review this document with you, and ask you to sign this informed consent document. After you have signed this document, and received a signed copy, the study will begin with a Screening Visit. Research studies are usually dividing into at least 3 parts, typically consisting of:  
1. Testing to see if you are eligible to participate in the study ("Screening");
2. Testing during study treatment to monitor your health and the effects of the study treatment
("Study Evaluation Procedures"); and 3. Testing after your treatment is complete ("Follow-up"). Testing/procedures for each of these parts are described separately below.
Following is an image that illustrating this study.  
 The first part of the study is screening. Eligible patients will continue to receive durvalumab and chemotherapy, and then have their bladder and remaining tumor removed (cystectomy). Most of the examinations, tests, or procedures will be part of your regular medical care, would be done even if you do not join the study. If you have had some of them recently, they may not need to be repeated.  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer

During the study, you will come into the clinic on Day 1 of each cycle to receive your treatment, and for tests to assess how well the treatments are working. You will also come into the clinic on Day 2 or Day 8 of each cycle, depending on your treatment group. At all clinic visits the doctors will ask about the medicines you are taking, and if you have any side effects. The tests that will occur on Day 1 of each cycle are described below. Physical examination: A physical exam will be performed, as described above. Blood collection: Blood will be collected, as described above. Up to about 2 tablespoons (30mLs) will be collected. Assessments on Day 2 or Day 8 of each cycle (depending on treatment assignment) will be limited to checking about the medicines you are taking, and if you have any side effects. During this study, you will have your bladder cancer surgically removed by cystectomy (surgical removal of your bladder). Before the surgery, your medical condition will be checked by a CT-CAP scan, as described above, and a small sample of blood will be collected (about 1 teaspoon, 5 mL). The study team will also check about the medicines you are taking, and if you have any side effects. Additional tests may be ordered by the doctor as determined medically necessary.

Research using tissues, such as from your research blood sample, is an important way to try to understand human disease. Sometimes, research may include the testing and study of genes, also known as DNA, and related materials called RNA, proteins, and/or metabolites. This type of testing is also called "genetic analysis" or called "pharmacogenomic research." You are being given this information because the Study Doctors want to include a sample of your blood in a research project and because they want to save the samples for future research. A previously-collected tumor sample may be adequate for this, or your doctor may need to collect a fresh sample of your tumor tissue for testing, which will include genetic analysis.  
  
Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer There are several things you should know before participating in this study and … allowing your blood to be studied. This subject is complicated, and there are many considerations. Ask for more information if you do not understand any part of this information. Genes are in every cell of your body. Your genes were inherited from your biological parents and carry instructions for the body to grow, develop, and survive. Genes are made of a substance called DNA. Most genes and DNA are identical among human beings, but there are small variations between different people. These small genetic differences are why people have their own unique characteristics, such hair color, eye color, height, and other characteristics. Some traits affected by genetics are not visible, such as why different people have different responses, including side effects, to the same drug, or are more likely to get certain diseases or conditions. The proteins in your body were determined by your genes, and control how your body works. Differences in genes and therefore proteins can affect the way a disease develops, the way drugs act against the disease, or the way your body uses the drugs. The purpose of this type of research is to understand the cause of disease, such as cancer, or the body's response to the treatments (such as safety findings or drug level patterns). In this study, the genetic research is being done learn more about variant histology bladder cancer, and what might be effective to improve treatment of this type of cancer. The data from your sample for this genetic research project will be used for research purposes only. This genetic research sample may be used for additional research including: additional studies of cancer; as a comparison sample ("control sample") in other cancer studies or in a group of other patients' samples to determine the natural difference in genes and proteins in groups of people with cancer; or to develop new gene research techniques. The results of future studies could trigger the need to test or re-test the genetic research samples; therefore, the sample and data generated from them will be held by Stanford and the company supporting this study (AstraZeneca/MedImmune) for many years. These samples, and the data generated from them, may be shared with other researchers or entered into databases, provided confidentiality is upheld (you are not identified), and they are used only for research on the topics described in this document. The information in these databases may be kept forever, however, information that could directly identify you will not be included in these databases. However, your privacy is very important to us and we will use safety measures to protect it. Despite all of the safety measures that we will use, we cannot guarantee that your identity will never become known. Although you will be told the results of study tests that are part of your regular medical care, the genetic testing described here will not be used for decisions about your medical care, and there may be no results from this genetic research for many years, therefore the results of the genetic testing may not be given to you, your doctor, or any other staff at the study center.

Your samples will be sent outside of Stanford for analysis. Your blood sample will be stored and identified by your unique study number ("study identifier") only, and not your name. This study identifier will be a series of numbers and/or letters. Donors of samples do not retain any property rights to the samples. You have the right to refuse to allow your tissues to be studied now or saved for future study. However, agreeing to provide this blood sample is required in order to participate in this study. If you choose not to provide the sample, you cannot participate in the study. Regular medical care will be available to treat your condition. You may withdraw from this study at any time. The Study Doctors might retain the identified samples, eg, as part of your routine clinical care, but not for additional research. An authorization statement for your initials is provided on the signature page of this document. Adverse event monitoring will be performed as part of the procedures described above. During the treatment period, the Study Doctors will monitor you for any potential side effects. If the side effects are severe, the Study Doctors may temporarily stop study medication; change the dosage of your study medication; or withdraw your medication completely. If, at any time, you have any symptom; side effect; or injury affecting you physically or mentally during the study, you should tell the Study **Doctors or nurses right away**, even if you do not think it was caused by the study medication.  
If you have to go to the hospital for any reason, please tell the hospital staff that you are participating on a research study, and give them the contact information for the study team. You may be provided with a card with the study team contact information.  
  
  
  
  
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer STUDY CALENDAR BY COHORT (all receive durvalumab)
Dose-Dense Methotrexate, Vinblastine, Doxorubicin, Cisplatin cohort ("DD MVAC" 14**-day Cycle)**  
| EOT                                          | Surgery                                                                                                                                      | ctDNA       | End of   |      |      |      |      |      |      |                |
|----------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------|-------------|----------|------|------|------|------|------|------|----------------|
| Safety                                       | Collection                                                                                                                                   | Study Visit |          |      |      |      |      |      |      |                |
| Visit                                        |                                                                                                                                              |             |          |      |      |      |      |      |      |                |
| Procedure                                    | Screeninga Cycle 1 Cycle 1 Cycle 2  Cycle 2 Cycle 3 Cycle 3 Cycle 4 Cycle 4  Day 1 c Day 2 c Day 1 c Day 2 c Day 1 c Day 2 c Day 1 c Day 2 c | 4 weeks  post             |          |      |      |      |      |      |      |                |
| cystectomy  (+/- 2  weeks)                   | 12 weeks  postcystectomy  (+/- 2  weeks)                                                                                                                                              |             |          |      |      |      |      |      |      |                |
| 4 weeksm                                     |                                                                                                                                              |             |          |      |      |      |      |      |      |                |
| Scheduling Window (Days)                     | -30 to -1                                                                                                                                    | (+2)        | (+2)     | (+2) | (+2) | (+2) | (+2) | (+2) | (+2) | (+/- 2  weeks) |
| Informed Consenth                            | X                                                                                                                                            |             |          |      |      |      |      |      |      |                |
| Medical history                              | X                                                                                                                                            |             |          |      |      |      |      |      |      |                |
| Physical exam                                | X                                                                                                                                            | X           | X        | X    | X    |      |      |      |      |                |
| Vital signs, weight, & heightd               | X                                                                                                                                            | X           | X        | X    | X    |      |      |      |      |                |
| ECOG Performance Status                      | X                                                                                                                                            | X           | X        | X    | X    |      |      |      |      |                |
| Complete blood count w/differential          | X f                                                                                                                                          | X           | X        | X    | X    |      |      |      |      |                |
| Comprehensive metabolic panel  including Mgi | X f                                                                                                                                          | X           | X        | X    | X    |      |      |      |      |                |
| Coagulation (PT, PTT, INR)                   | X                                                                                                                                            |             |          |      |      |      |      |      |      |                |
| TSH                                          | X                                                                                                                                            |             |          |      |      |      |      |      |      |                |
| Urinalysis                                   | X                                                                                                                                            |             |          |      |      |      |      |      |      |                |
| Hepatitis B serology                         | X                                                                                                                                            |             |          |      |      |      |      |      |      |                |
| Hepatitis C serology                         | X                                                                                                                                            |             |          |      |      |      |      |      |      |                |
| Participant ID:                              | Page 10 of 40                                                                                                                                |             |          |      |      |      |      |      |      |                |  
  
IRB Use Only  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer  
| HIV serology                        | X   |    |     |    |    |    |    |    |    |
|-------------------------------------|-----|----|-----|----|----|----|----|----|----|
| Pregnancy test                      | X   |    |     |    |    |    |    |    |    |
| Biomarkersk                         | X   | X  | X   | X  | X  |    |    |    |    |
| 12-lead ECGg                        | X   |    |     |    |    |    |    |    |    |
| ECHO                                | X   |    |     |    |    |    |    |    |    |
| Tumor specimen testing              | X   | X  |     |    |    |    |    |    |    |
| CT or MRI of abdomen and pelvise    | X   | X  | X L |    |    |    |    |    |    |
| CT or X-ray of cheste               | X   |    |     |    |    |    |    |    |    |
| Bone scan (if alk phos is elevated) | X   |    |     |    |    |    |    |    |    |
| Adverse event collection            | X   | X  | X   | X  | X  | X  | X  | X  |    |
| Concomitant medications             | X   | X  | X   | X  | X  | X  | X  | X  | X  |
| TREATMENT                           |     |    |     |    |    |    |    |    |    |
| Durvalumab (750mg)                  | X   | X  | X   | X  |    |    |    |    |    |
| Methotrexate                        | X   | X  | X   | X  |    |    |    |    |    |
| Vinblastine                         | X   | X  | X   | X  |    |    |    |    |    |
| Doxorubicin                         | X   | X  | X   | X  |    |    |    |    |    |
| Cisplatin                           | X   | X  | X   | X  |    |    |    |    |    |
| Cystectomyj                         | X   |    |     |    |    |    |    |    |    |  
  
IRB Use Only Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer  
| Cisplatin plus Gemcitabine cohort ("Cis-Gem," 21-day cycle)   | EOT                                                                                                                                  | Surgery     | ctDNA   | End of   |      |         |      |         |      |                |
|---------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------|-------------|---------|----------|------|---------|------|---------|------|----------------|
| Safety                                                        | Collection                                                                                                                           | Study Visit |         |          |      |         |      |         |      |                |
| Visit                                                         |                                                                                                                                      |             |         |          |      |         |      |         |      |                |
| Procedure                                                     | Screeninga Cycle 1 Cycle 1 Cycle 2  Cycle 2 Cycle 3 Cycle 3 Cycle 4 Cycle 4  Day 1 b Day 8 Day 1 b Day 8 Day 1 b Day 8 Day 1 b Day 8 | 4 weeks  post             |         |          |      |         |      |         |      |                |
| cystectomy  (+/- 2  weeks)                                    | 12 weeks  postcystectomy  (+/- 2  weeks)                                                                                                                                      |             |         |          |      |         |      |         |      |                |
| 4 weeksm                                                      |                                                                                                                                      |             |         |          |      |         |      |         |      |                |
| Scheduling Window (Days)                                      | -30 to -1                                                                                                                            | (+/- 2)     | (+2)    | (+/- 2)  | (+2) | (+/- 2) | (+2) | (+/- 2) | (+2) | (+/- 2  weeks) |
| Informed Consenth                                             | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| Medical history                                               | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| Physical exam                                                 | X                                                                                                                                    | X           | X       | X        | X    |         |      |         |      |                |
| Vital signs, weight, & heightd                                | X                                                                                                                                    | X           | X       | X        | X    |         |      |         |      |                |
| ECOG Performance Status                                       | X                                                                                                                                    | X           | X       | X        | X    |         |      |         |      |                |
| f                                                             | X                                                                                                                                    | X           | X       | X        |      |         |      |         |      |                |
| Complete blood count w/differential                           | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| Comprehensive metabolic panel                                 | X f                                                                                                                                  | X           | X       | X        | X    |         |      |         |      |                |
| including Mgi Coagulation (PT, PTT, INR)                      | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| TSH                                                           | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| Hepatitis B serology                                          | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| Urinalysis                                                    | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| Hepatitis C serology                                          | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| HIV serology                                                  | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| Pregnancy test                                                | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| Biomarkersk                                                   | X                                                                                                                                    | X           | X       | X        | X    |         |      |         |      |                |
| 12-lead ECGg                                                  | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| ECHO                                                          | X                                                                                                                                    |             |         |          |      |         |      |         |      |                |
| Participant ID:                                               |                                                                                                                                      |             |         |          |      |         |      |         |      |                |  
  
  
IRB Use Only  
  
  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer  
| Tumor specimen testing              | X   | X   |     |    |    |    |    |    |    |
|-------------------------------------|-----|-----|-----|----|----|----|----|----|----|
| CT or MRI of abdomen and pelvise    | X   | X   | X L |    |    |    |    |    |    |
| CT or X-ray of cheste               | X   |     |     |    |    |    |    |    |    |
| Bone scan (if alk phos is elevated) | X   |     |     |    |    |    |    |    |    |
| Adverse event collection            | X   | X   | X   | X  | X  | X  | X  | X  |    |
| Concomitant medications             | X   | X   | X   | X  | X  | X  | X  | X  | X  |
| TREATMENT                           |     |     |     |    |    |    |    |    |    |
| Durvalumab (1500mg)                 | X   | X   | X   | X  |    |    |    |    |    |
| Cisplatin                           | X   | X   | X   | X  |    |    |    |    |    |
| Gemcitabine                         | X   | X   | X   | X  | X  | X  | X  | X  |    |
| Cystectomyj                         | X   |     |     |    |    |    |    |    |    |  
  
IRB Use Only Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer  
| Carboplatin plus Gemcitabine cohort ("Carbo-Gem," 21-day cycle)                | EOT           | Surgery                                                                                                                   | ctDNA   | End of Study   |      |         |      |         |      |
|--------------------------------------------------------------------------------|---------------|---------------------------------------------------------------------------------------------------------------------------|---------|----------------|------|---------|------|---------|------|
| Safety                                                                         | Collection    | Visit                                                                                                                     |         |                |      |         |      |         |      |
| Visit                                                                          |               |                                                                                                                           |         |                |      |         |      |         |      |
| Procedure                                                                      | Screeninga    | Cycle 1 Cycle 1 Cycle 2  Cycle 2 Cycle 3 Cycle 3 Cycle 4 Cycle 4  Day 1 Day 8 b Day 1 Day 8 b Day 1 Day 8 b Day 1 Day 8 b | 4       |                |      |         |      |         |      |
| weeksm (+/- 2  weeks)                                                          | 4 weeks  post               |                                                                                                                           |         |                |      |         |      |         |      |
| cystectomy  (+/- 2 weeks)                                                      | 12 weeks  postcystectomy  (+/- 2 weeks)               |                                                                                                                           |         |                |      |         |      |         |      |
| Scheduling Window (Days)                                                       | -30 to -1     | (+/- 2)                                                                                                                   | (+2)    | (+/- 2)        | (+2) | (+/- 2) | (+2) | (+/- 2) | (+2) |
| Informed Consenth                                                              | X             |                                                                                                                           |         |                |      |         |      |         |      |
| Medical history                                                                | X             |                                                                                                                           |         |                |      |         |      |         |      |
| Physical exam                                                                  | X             | X                                                                                                                         | X       | X              | X    |         |      |         |      |
| Vital signs, weight, & heightd                                                 | X             | X                                                                                                                         | X       | X              | X    |         |      |         |      |
| ECOG Performance Status                                                        | X             | X                                                                                                                         | X       | X              | X    |         |      |         |      |
| Complete blood count                                                           | X f           | X                                                                                                                         | X       | X              | X    |         |      |         |      |
| w/differential Comprehensive metabolic panel                                   | X f           | X                                                                                                                         | X       | X              | X    |         |      |         |      |
| including Magnesiumi Coagulation (PT, PTT, INR)                                | X             |                                                                                                                           |         |                |      |         |      |         |      |
| TSH                                                                            | X             |                                                                                                                           |         |                |      |         |      |         |      |
| Urinalysis                                                                     | X             |                                                                                                                           |         |                |      |         |      |         |      |
| Hepatitis B serology                                                           | X             |                                                                                                                           |         |                |      |         |      |         |      |
| Hepatitis C serology                                                           | X             |                                                                                                                           |         |                |      |         |      |         |      |
| HIV serology                                                                   | X             |                                                                                                                           |         |                |      |         |      |         |      |
| Pregnancy test                                                                 | X             |                                                                                                                           |         |                |      |         |      |         |      |
| BiomarkersK                                                                    | X             | X                                                                                                                         | X       | X              | X    |         |      |         |      |
| 12-lead ECGg                                                                   | X             |                                                                                                                           |         |                |      |         |      |         |      |
| ECHO                                                                           | X             |                                                                                                                           |         |                |      |         |      |         |      |
| Participant ID:                                                                | Page 14 of 40 |                                                                                                                           |         |                |      |         |      |         |      |
| Sandy Srinivas, MD / IRB-48062 Protocol Amendment v5; ICF v4 dated 14 MAY 2020 |               |                                                                                                                           |         |                |      |         |      |         |      |  
MD  
  
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer  
| Tumor specimen testing                                                                              | X   | X   |     |    |    |    |    |    |    |
|-----------------------------------------------------------------------------------------------------|-----|-----|-----|----|----|----|----|----|----|
| CT or MRI of abdomen and pelvise                                                                    | X   | X   | X L |    |    |    |    |    |    |
| CT or X-ray of cheste                                                                               | X   |     |     |    |    |    |    |    |    |
| Bone scan (if alk phos is elevated)                                                                 | X   |     |     |    |    |    |    |    |    |
| Adverse event collection                                                                            | X   | X   | X   | X  | X  | X  | X  | X  |    |
| Concomitant medications                                                                             | X   | X   | X   | X  | X  | X  | X  | X  | X  |
| TREATMENT                                                                                           |     |     |     |    |    |    |    |    |    |
| Durvalumab (1500mg)                                                                                 | X   | X   | X   | X  |    |    |    |    |    |
| Carboplatin                                                                                         | X   | X   | X   | X  |    |    |    |    |    |
| Gemcitabine                                                                                         | X   | X   | X   | X  | X  | X  | X  | X  |    |
| Cystectomyj                                                                                         | X   |     |     |    |    |    |    |    |    |
| a: Subjects must be screened within 30 days prior to Cycle 1 Day 1 with the exception of some labs. |     |     |     |    |    |    |    |    |    |  
a: Subjects must be screened within 30 days prior to Cycle 1 Day 1 with the exception of some labs. b: For Cis/Gem and Carbo/Gem cohorts there must be at least 7 days between Day 1 and Day 8. c: Efforts should be made to conduct study visits on the day scheduled (+2 days). Delays in dosing will shift the following cycle so that there are at least 12 days between Day 8 of the previous cycle and Day 1 of the current cycle.  
d: Assessments will include vital signs (resting BP HR, RR, and body temperature) and weight. Height will be recorded at screening.  
e: PET CT for subjects with impaired renal function is an acceptable alternative.  
f: within 28 days of Cycle 1 Day 1 g: ECGs should be obtained after the subject has been in a supine position for 5 minutes and recorded while the subject remains in that position. In case of clinically significant ECG abnormalities, including a QTcF value > 470 ms; 2 additional 12 lead ECGs should be obtained over a brief period (eg, 30 minutes) to confirm the finding.  
h: Informed consent may be obtained greater than 30 days prior to first dose of study treatment. i: Magnesium is to be performed at baseline on Day 1 and as clinically indicated j: Within 6 weeks post completion of 4 cycles k: Biomarkers sample to be collected at pre-initiation of neoadjuvant treatment, upon completion of neoadjuvant treatment and prior to surgical cystectomy, 4 weeks (+/- 2 weeks) post-cystectomy and 12 weeks (+/- 2 weeks) post cystectomy L: May be completed within 7 days before the End of Study visit m: within 4 weeks ± 2 weeks of completion of neoadjuvant treatment, typically at the subject's cystectomy pre-operative visit  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer
Clinical trial: NCT03912818
Section: Purpose of Research
Subsections: Purpose Of Research

The proposed study is called a Phase 2 "neoadjuvant" chemotherapy study. Neoadjuvant treatment, means to receive chemotherapy and/or radiation therapy before surgery. The study team hopes to learn if durvalumab, administered in combination with standard  
  
  
  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer chemotherapy, is safe, and if there is any beneficial effect of durvalumab in combination with chemotherapy to treat variant histology bladder cancer. Your doctor recommends chemotherapy as the best treatment choice that is available to you at this time. Other than durvalumab administration, there are no other research aspects of this study. Your normal medical care for your bladder cancer would be the same or similar chemotherapy. The current standard anti-cancer treatment for your cancer includes combinations of drugs known as methotrexate; gemcitabine; carboplatin; cisplatin; vinblastine; and doxorubicin. Using current therapies, some patients with variant histology bladder cancer receive treatment benefit but are not cured of their disease. Your normal medical care would also include medical exams, blood tests, and medical scans to check the status of your cancer such as positron emission tomography (PET); computed tomography (CT); or magnetic resonance imaging (MRI) scans. Your normal medical care might also include radiation treatments, depending on the details of your cancer. This study does not include radiation treatment. The other parts of this study that are research (experimental, not part of your regular care) are the use and administration of durvalumab. Durvalumab is approved by FDA as "Imfinzi" for the treatment of people with locally-advanced or metastatic urothelial carcinoma that progressed (got worse) during or after platinum-containing chemotherapy or had disease progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.  
"Neoadjuvant" therapy means to receive chemotherapy and/or radiation therapy before surgery. "Adjuvant" therapy means having the surgery first, followed by chemotherapy and/or radiation therapy. For this study, durvalumab will be provided by the drug manufacturer AstraZeneca/MedImmune. If you decide to terminate your participation in this study, you should notify Dr Srinivas at 650-725-2078. This research study is looking for up to 24 patients with variant histology bladder cancer. The study is being done at about only at the Stanford University Medical Center.
Clinical trial: NCT03912818
Section: Voluntary Participation
Subsections: Voluntary Participation

Your participation in this study is entirely voluntary. Your decision not to participate will not have any negative effect on you or your medical care. You can decide to participate now but withdraw your consent later and stop being in the study without any loss of benefits or medical care to which you are entitled.
Clinical trial: NCT03912818
Section: Withdrawal from Study
Subsections: Withdrawal From The Study

If you first agree to participate and then you change your mind, you are free to withdraw your consent and discontinue your participation at any time. Your decision will not affect your ability to receive medical care for your disease and you will not lose any benefits to which you would otherwise be entitled. If you decide to withdraw your consent to participate in this study, you should notify Sandy Srinivas, MD at 650-725-2078. If you withdraw after starting treatment with the durvalumab, your Study Doctor will need to check on your health status afterwards. If you do not want the Study Doctor to check on your health status after withdrawing from the study, you should say so. Any information collected before you withdraw will be kept and used to complete the research.  
  
  
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer To help you safely finish your participation in the study, the Study Doctors may ask you to have more tests and you will be asked to come into the clinic for an End-of-Treatment Visit after stopping durvalumab. The Study Doctor will discuss your treatment options with you at this time. If you withdraw from the study, or the study medication is stopped for any reason, Your cancer may get worse. To help you leave the study safely, the Study Doctors may ask you to have more tests. The Study Doctors may also ask if you wish to take part in the follow-up portion of the study. If you agree to continue with the follow-up portion of the study, information about your health will continue to be collected as described above in the Follow-up Procedures section.  
The Study Doctor will discuss with you the different withdrawal decisions, including your options for continued treatment. Data and information from your participation may not be removed from the research study database and may continue to be used to complete the research analysis. This is discussed in more detail under the heading "Authorization To Use Your Health Information For Research Purposes" on the following pages.  
Your treatment in this study can continue until one of the following occurs:
You withdraw your agreement to continue to take part in this research study; The Study Doctor withdraws you from the study, and the study medication is stopped, with or without your consent, for one or more of the following reasons:
o Failure to follow the instructions of the Protocol Director and study team o The Study Doctor decides that continuing your participation could be harmful to you, or otherwise not in your best interest o Your cancer becomes worse (tumor progression) o If you have bad side effects during treatment with durvalumab, or if you or your doctor otherwise decide that the side effects are too severe or undesirable o You have a different illness that prevents further administration of durvalumab o You need treatment with drugs or procedures not allowed in the study.  
o You have become pregnant o The study is stopped by the company supporting the study
(AstraZeneca/MedImmune); the Study Doctor; the Stanford Institutional Review Board (the IRB, a group of people who review the research to protect your rights), or by a regulatory agency such as the US FDA
o Other administrative reasons o Unanticipated circumstances When your participation in this study ends, you may be asked to return for a final visit to have some end-of-study evaluations or tests, or to allow medical information to be collected about your health after the trial treatment is stopped. After you finish the study, or stop taking the durvalumab for any other reason, you may continue to be checked regularly (physical exams; blood tests; tumor measurements; X-rays; other scans, etc) if you continue to have significant side effects from the treatment. This is called follow-up. Your Study Doctor will follow your  
  
Approval Date: February 9, 2022 Expiration Date: February 9, 2023
MD
Protocol Title: Phase 2 Open Label Study of Durvalumab with Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer progress, in accordance with good medical care, for as long as it is felt to be necessary by both you and the doctor, unless you ask otherwise. Many if not all of these procedures will be part of your regular continued medical care. In addition, further treatment outside the study will be discussed with you.