Clinical trial: NCT01748825
Section: Alternatives
Subsections: Alternative Approaches Or Treatments What Other Choices Do I Have If I Do Not Take Part In This Study?

Instead of being in this study, you have these options:
Getting treatment or care for your cancer without being in a study Taking part in another study Getting comfort care, also called palliative care. This type of care helps reduce pain, tiredness, appetite problems, and other problems caused by the cancer. It does not treat the cancer directly. Instead, it tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.  
Please talk to your doctor about these and other options.
Clinical trial: NCT01748825
Section: Duration of Study Involvement
Subsections: Follow-Up

You will be followed for 30 days after taking the last dose of study drugs. We will call you between days 27-30 to ask about any side effects that were ongoing when you stopped therapy, or any new side effects that might be related to the study therapy. If you have side effects that might be related to the study drugs that have not gotten better after 30 days, we will call you every 2 weeks until the side effects have become stable or gotten better. The follow-up period will end if you enroll in another study or start receiving standard therapy.
Clinical trial: NCT01748825
Section: Participant's Rights
Subsections: Research Subject'S Rights What Are My Rights If I Take Part In This Study?

Taking part in this study is your choice. You may choose either to take part or not to take part in this study. If you decide to take part, you may leave the study at any time. No matter what decision you make, there will be no penalty to you, and you will not lose any of your regular benefits. Leaving the study will not affect your medical care. You can still get your medical care from our institution if you are eligible and choose to participate in another trial. We will tell you about new information or changes in the study that may affect your health or your willingness to continue in the study. In the case of injury resulting from this study, you do not lose any of your legal rights to seek payment by signing this form.
Clinical trial: NCT01748825
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation What Possible Risks Can I Expect From Taking Part In This Study?|Reproductive Risks:|Potential Risks Related To Research-Related Imaging Studies:|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

If you choose to take part in this study, there is a risk that: - You may lose time at work or home and spend more time in the hospital or doctor's office than usual
- You may be asked sensitive or private questions which you normally do not discuss  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent  
The AZD1775 used in this study may affect how different parts of your body work such as your liver, kidneys, heart, and blood. The study doctor will be testing your blood and will let you know if changes occur that may affect your health.  
There is also a risk that you could have side effects from the study drug(s)/study approach. Here are important points about side effects: - The study doctors do not know who will or will not have side effects. - Some side effects may go away soon, some may last a long time, or some may never go away. - Some side effects may interfere with your ability to have children. - Some side effects may be serious and may even result in death. Here are important points about how you and the study doctor can make side effects less of a problem: - Tell the study doctor if you notice or feel anything different so they can see if you are having a side effect.  
- The study doctor may be able to treat some side effects. - The study doctor may adjust the study drugs to try to reduce side effects. We do not know if taking AZD1775 will cause any other medications you may be taking to work differently. It is very important that you tell a member of the research team before starting any new drugs, over-the-counter medications, or alternative therapies. You will also receive a list of medications, vitamins, and supplements that should be avoided while taking part in the study. All herbal supplements and medications should be avoided while participating in the study. Grapefruit and Seville oranges and their products (including marmalade, juice, etc.) should be avoided while taking part in the study. The tables below show the most common and the most serious side effects that researchers know about. There might be other side effects that researchers do not yet know about. If important new side effects are found, the study doctor will discuss these with you. Some patients on this study have experienced anaphylaxis, or a severe allergic reaction, possibly related to the study drug. This condition can cause difficulty breathing, increased heart rate, decreased blood pressure, skin rash, dizziness, nausea, and vomiting. Anaphylaxis can be lifethreatening.  
The risks and side effects associated with AZD1775 are presented below and are based on 3 completed studies. You will be closely followed for these risks and side effects.  
COMMON, SOME MAY BE SERIOUS
In 100 people receiving AZD1775 (adavosertib), more than 20 and up to 100 may have:
Diarrhea, nausea, vomiting Tiredness  
OCCASIONAL, SOME MAY BE SERIOUS  
In 100 people receiving AZD1775 (adavosertib), from 4 to 20 may have:  
Anemia which may require blood transfusion  
Pain  
Constipation, heartburn  
Sores in the mouth which may cause difficulty swallowing Swelling of the body  
Fever  
Infection, especially when white blood cell count is low Bruising, bleeding Loss of appetite, dehydration Dizziness, headache  
Difficulty sleeping Cough, shortness of breath  
Rash  
RARE, AND SERIOUS  
In 100 people receiving AZD1775 (adavosertib), 3 or fewer may have:  
Abnormal heartbeat  
Bleeding from multiple sites  
Internal bleeding which may cause black tarry stool, blood in vomit  
Damage to the liver Change in the heart rhythm  
Bleeding in the brain which may cause confusion

If you are a woman who is breastfeeding or pregnant, you may not take part in the study because we do not know how AZD1775 would affect your baby or your unborn child. If you are a woman on this study who may become pregnant, you should not become pregnant while on this study and for 2 months after you stop taking the drug because the drugs in this study can affect an unborn baby. It is important you understand that women who may become pregnant need to use birth control for at least two weeks before the start of this study, while on this study, and for 2 months after the study. If you are a man on this study, you should not father a baby or donate sperm while on this study or for 3 months after you stop taking the drug because the drugs in this study can affect an unborn baby. It is important you understand that men on this study and their female partners who may become pregnant need to use birth control while on this study and for 3 months after the study. If you are a man with a female partner who is pregnant or not using effective birth control, you should abstain while on this study and for 3 months after you stop taking the drug. If you are a man who wishes to father children while on this study, you should arrange for the freezing of sperm samples prior to the start of the study. Check with your study doctor about what kind of birth control methods to use and how long to use them. Some methods might not be approved for use in this study. If you think that you or your partner is pregnant, you should tell your study doctor or nurse at once. Patients who become pregnant while taking part in the study will be taken off the study. Effective forms of birth control include:
- abstinence  intrauterine device (IUD)
- hormonal [birth control pills, injections, or implants] - tubal ligation - vasectomy - barrier methods (condoms)

This research study involves exposure to radiation from up to 3 CT scans (used in biopsy collections). This radiation exposure is not required for your medical care and is for research purposes only. The amount of radiation you will receive in this study is 2.4 rem, which is below the guideline of 5 rem per year allowed for research subjects by the NIH Radiation Safety Committee. The average person in the United States receives a radiation exposure of 0.3 rem per year from natural sources, such as the sun, outer space, and the earth's air and soil. If you would like more information about radiation, please ask the investigator for a copy of the pamphlet, An Introduction to Radiation for NIH Research Subjects. While there is no direct evidence that the amount of exposure received from participating in this study is harmful, there is indirect evidence it may not be completely safe. There may be a very slight increase in the risk of cancer. Please tell your doctor if you have had any radiation exposure in the past year, either from other research studies or from medical tests or care, so we can make sure that you will not receive too much radiation. Radiation exposure includes x-rays taken in radiology departments, cardiac catheterization, and fluoroscopy as well as nuclear medicine scans in which radioactive materials were injected into your body. If you are pregnant you will not be permitted to participate in this research study.

The aim of this study is to see if this experimental treatment will cause your tumors to shrink.  
We do not know if you will receive personal, medical benefit from taking part in this study.  
These potential benefits could include shrinking of your tumor or lessening of your symptoms, such as pain, that are caused by the cancer. Because there is not much information about the drug's effect on your cancer, we do not know if you will benefit from taking part in this study, although the knowledge gained from this study may help others in the future who have cancer.
Clinical trial: NCT01748825
Section: Procedures
Subsections: Description Of Research Study What Will Happen If You Take Part In This Research Study?|Standard Procedures Being Done Because You Are In This Study; These May Be Done More Often Because You Are In The Study:

Before you begin the study You will need to have the following examinations, tests, or procedures to find out if you can be in the study. These tests are part of your regular cancer care and should be done by your health care team even if you do not join the study. If you have had them recently, they may not need to be repeated. This will be up to your study doctor. Willingness to give blood and urine samples for research is required for taking part in this study. If you decide that you would like to participate in this study, you will be asked to sign this consent form. You will then have the examinations, tests, and procedures listed below done to see if you can take part in the study (this is called the screening/baseline evaluation).

**Clinic visit:** to ask how you are feeling and to evaluate you with a physical examination during week 1 and 2 of cycle 1, and then at the beginning of each cycle.  
**Vital signs and physical examinations:** will be performed during the clinic visits.  
**Blood tests:** Measurement of your white blood cells, red blood cells, platelets, blood sugar, electrolytes, and of how your liver and kidneys work will be done every week during cycle 1, and then at the beginning of every cycle. Approximately 1 tablespoon (15 mL) of blood will be drawn per visit.  
**CT scans** or other imaging tests such as ultrasound (an examination using sound waves) or MRI (an examination using magnetic field and radio waves) that detect your tumor will be done before the study and every 6 weeks while you are receiving study drugs (every 9 or 12 weeks if you have been on study for a year or 3 years). This is done so that any benefit of the treatment can be determined, and if your cancer is not responding to the treatment, the study team can tell you and discuss other treatment options (discussed further below).  
Tests and procedures that are either being tested in this study or being done to see how the drug is affecting your body:
**Measurement of AZD1775 in your blood:** We will collect blood samples to measure the amount of study drug in the blood and to help us find out how the body handles the drug. Blood will be collected at multiple time points during cycle 1 only. Please see the study chart for more details. The total blood for all these tests will be about 6 tablespoons (90 mL). Willingness to give these blood samples is required for taking part in this study. Any blood samples remaining after analysis of AZD1775 may be used for analyses of other compounds related to how the body handles AZD1775 or how the drug affects the body.  
**Other research blood samples:** We will also be collecting optional blood samples from some patients to find out the effects of the drug on any tumor cells in the blood. Blood samples will be collected at the following times during every cycle: day 1, day 4, day 8 (both before and after receiving drug), and day 11, and then every time we do a CT scan to find out how your tumor is responding to the treatment. Each blood collection is about 2 teaspoons (8 mL). In addition, we will be collecting optional blood samples to find out if there are any effects from the drug on your immune system at the beginning of the study and on day 8 of cycle 1. The total amount of blood collected for this optional study is approximately 18 tablespoons (270 mL), though this will vary depending how long you are on study. We will tell you when blood for research will be collected.  
**Tumor Biopsy:** After you are accepted to take part in the study, you will be asked to undergo imaging-directed biopsy of your tumor (removal of a small bit of tissue for microscopic examination) once before you receive the study drug and a second time a few days later. We are collecting biopsy samples to study the effects of AZD1775 on your tumor. Biopsies are an important part of this trial and are done for research purposes. If you have already had a recent tumor biopsy for research we may be able to use this instead for your before-study biopsy if you haven't had any treatment since it was collected and it is of good quality. During the early stage of the study only, a patient may choose to not undergo biopsies, and this will not affect his or her taking part in this study. During that time, if a patient decides not to have one or both biopsies collected, he or she will still receive AZD1775 and other tests that are part of the study and detailed above. However, at a certain point in this study, willingness to undergo tumor biopsies will be required for taking part in this study. We will tell you if biopsies are required before you decide to take part in the study.  
We may also ask you for an optional third biopsy if your disease comes back or shows signs of coming back during treatment. You will be asked to sign a separate consent form for each biopsy procedure.  
Tumor biopsies are only collected by trained personnel. Biopsies are collected using a small needle under imaging guidance (CT, MRI, or ultrasound as deemed appropriate by the interventional radiologist performing the biopsy). Imaging helps the specialized radiologist know that the needle has been placed into the tumor mass. Typical risks of biopsy collection include, but are not limited to, bleeding, infection, pain, and scarring. If you experience any complications from the biopsy, medical care will be offered to you. You will be counseled in more detail about biopsies, and you will be asked to sign a separate consent form that will describe the procedures and risks at that time. Your safety is the most important thing at all times. If upon attempting the first biopsy, no tissue can be obtained or it has caused you harm, further biopsies will not be done. After you are enrolled in this study, if for any reason the biopsies cannot be done safely, you may still receive the study drugs but the biopsies will not be done. I agree to allow biopsies for research purposes:
Yes No Initials_________
Clinical trial: NCT01748825
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

We are doing this study to try to develop better treatments for cancer. In this study and experimental drug, AZD1775 (formerly known as MK-1775), will be given to you. The purpose of this study is to test the safety of AZD1775 and find out the dose of the drug that can be safely given to humans. We are trying to understand how AZD1775 works in humans, how your body handles this drug, what side effects the drug causes, and the safety of the drug at the given dose. AZD1775 is thought to work by blocking a protein that affects other proteins inside the cell that are known to be important in the growth of cancer. It is an experimental drug that has shown some anti-  
PATIENT IDENTIFICATION CONSENT TO PARTICIPATE IN A CLINICAL **RESEARCH**  
STUDY  
- Adult Patient or •Parent, for Minor Patient NIH-2514-1 (07-09) P.A.: 09-25-0099 File in Section 4: Protocol Consent (1)  
cancer effects against tumor cells in the laboratory and in experimental animals. This drug is in the beginning stages of being tested in humans.  
Why are you being asked to take part in this study?  
You are being asked to take part in this research study because you have advanced cancer that has progressed after receiving standard treatment, or for which no effective therapy exists.