Clinical trial: NCT02298946
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: NCT02298946
Section: Confidentiality
Subsections: 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 National Cancer Institute (NCI) and other government agencies, like the Food and Drug Administration (FDA), which are involved in keeping research safe for people.  
- National Cancer Institute Institutional Review Board
- The study Sponsor, Center for Cancer Research or their agent(s). - Qualified representatives from Amplimmune, Inc, the pharmaceutical company who produces AMP-224.
Clinical trial: NCT02298946
Section: Duration of Study Involvement
Subsections: During The Study|When You Are Finished Taking The Drugs (Treatment)

If the exams, tests and procedures show that you can be in the study, and you choose to take part, then you will begin treatment. Before you begin treatment you will have a mandatory biopsy of your tumor using a needle. You will have another mandatory biopsy of your tumor around day 29 after you start treatment unless you were unable to tolerate the first biopsy. Treatment involves receiving Cyclophosphamide (CTX) through your vein (IV) and SBRT on day 0 and AMP-224 through an IV once every 2 weeks for 6 doses. After you have completed the first two doses of AMP-224, you will have another biopsy of your tumor. If your disease is responding and you are tolerating the treatment well you will have the option of continuing the same every two week dose schedule until your disease shows clear evidence of growth. SBRT begins with a treatment planning session, which involves using imaging (4D computerized tomography) to precisely map the exact position of the tumor to be treated. These images are then used to create customized treatment plans in which sophisticated computerized devices direct several radiation beams of different intensities at different angles, so that the radiation is directed precisely to the tumor. The dose of AMP-224 is 10 milligrams per kilogram (a unit of body weight equal to about 2.2 pounds). AMP-224 will be administered over a minimum of 2 hours in the first treatment cycle. For subsequent treatment cycles, AMP-224 will be administered over a minimum of 1 hour. The AMP-224 infusion duration may be increased for patient safety at any time at the Investigator's discretion. CTX and AMP-224 will be administered on different days as an intravenous (injected into a blood vessel through a plastic tube or needle) injection. There are two groups of patients on the study. The first group of patients will receive one dose of radiation treatment (the SBRT). We plan to treat approximately 6 patients like this and this will be the first part of the study. Once the first part of the study is complete we will enroll new patients to the second part of the study. In this part of the study patients will receive 3 doses of the SBRT. In other words the main difference between the first and second parts of the study will the length of time you receive the radiation - either one or three doses.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
STUDY NUMBER: 15-C-0021 CONTINUATION: page 4 of 15 pages

You will be seen weekly for three weeks, then every two weeks for one month, then month two, and month five after that after completion of the study treatment to assess for possible delayed or ongoing side effects and overall clinical status. At these visit, you will have basic blood tests as well as blood collected for research purposes.  
| Study Chart Day 0      | -                                                                                                                         | History and physical exam   |
|------------------------|---------------------------------------------------------------------------------------------------------------------------|-----------------------------|
| -                      | Review of current medications and treatments                                                                              |                             |
| -                      | Routine blood tests                                                                                                       |                             |
| -                      | Stereotactic body radiation therapy                                                                                       |                             |
| -                      | CTX infusion                                                                                                              |                             |
| Day 1                  | -                                                                                                                         | Physical exam               |
| -                      | Vital Signs                                                                                                               |                             |
| -                      | Review of current medications and treatments                                                                              |                             |
| -                      | Routine and research blood tests                                                                                          |                             |
| -                      | Routine urine tests                                                                                                       |                             |
| -                      | ECG                                                                                                                       |                             |
| -                      | Report any side effects                                                                                                   |                             |
| -                      | Pre-medications                                                                                                           |                             |
| -                      | AMP-224 Infusion                                                                                                          |                             |
| Day 8                  | -                                                                                                                         | Physical exam               |
| -                      | ECG                                                                                                                       |                             |
| -                      | Report any side effects                                                                                                   |                             |
| -                      | Review of current medications and treatments                                                                              |                             |
| -                      | Routine and research blood tests                                                                                          |                             |
| Day 15                 | -                                                                                                                         | Physical exam               |
| -                      | Vital Signs                                                                                                               |                             |
| -                      | Review of current medications and treatments                                                                              |                             |
| -                      | Routine and research blood tests                                                                                          |                             |
| -                      | Routine urine tests                                                                                                       |                             |
| -                      | Report any side effects                                                                                                   |                             |
| -                      | Pre-medications                                                                                                           |                             |
| -                      | AMP-224 Infusion                                                                                                          |                             |
| Day 29                 | -                                                                                                                         | Physical exam               |
| -                      | Vital Signs                                                                                                               |                             |
| -                      | Review of current medications and treatments                                                                              |                             |
| -                      | Routine and research blood tests                                                                                          |                             |
| -                      | Routine urine tests                                                                                                       |                             |
| PATIENT IDENTIFICATION | CONTINUATION SHEET for either: NIH-2514-1 (07-09) NIH-2514-2 (10-84) P.A.: 09-25-0099 File in Section 4: Protocol Consent |                             |  
STUDY NUMBER: 15-C-0021 CONTINUATION: page 5 of 15 pages  
| -      | Tumor Biopsy                                 |               |
|--------|----------------------------------------------|---------------|
| -      | Report any side effects                      |               |
| -      | Pre-medications                              |               |
| -      | AMP-224 Infusion                             |               |
| Day 43 | -                                            | Physical exam |
| -      | Vital Signs                                  |               |
| -      | Review of current medications and treatments |               |
| -      | Routine and research blood tests             |               |
| -      | Routine urine tests                          |               |
| -      | Report any side effects                      |               |
| -      | Pre-medications                              |               |
| -      | AMP-224 Infusion                             |               |
| Day 57 | -                                            | Physical exam |
| -      | CT Scan or MRI                               |               |
| -      | Vital Signs                                  |               |
| -      | Review of current medications and treatments |               |
| -      | Routine and research blood tests             |               |
| -      | Routine urine tests                          |               |
| -      | Report any side effects                      |               |
| -      | Pre-medications                              |               |
| -      | AMP-224 Infusion                             |               |
| Day 71 | -                                            | Physical exam |
| -      | Vital Signs                                  |               |
| -      | Review of current medications and treatments |               |
| -      | Routine and research blood tests.            |               |
| -      | Routine urine tests                          |               |
| -      | Report any side effects                      |               |
| -      | Pre-medications                              |               |
| -      | AMP-224 Infusion                             |               |
Clinical trial: NCT02298946
Section: Participant's Rights
Subsections: Research Subject'S Rights What Are The Costs Of Taking Part In This Study?

If you choose to take part in the study, the following will apply, in keeping with the NIH policy:  
- You will receive study treatment at no charge to you. This may include surgery, medicines, laboratory testing, x-rays or scans done at the Clinical Center, National Institutes of Health (NIH), or arranged for you by the research team to be done outside the Clinical Center, NIH if the study related treatment is not available at the NIH.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
STUDY NUMBER: 15-C-0021 CONTINUATION: page 11 of 15 pages  
- There are limited funds available to cover the cost of some tests and procedures performed outside the Clinical Center, NIH. You may have to pay for these costs if they are not covered by your insurance company.  
- Medicines that are not part of the study treatment will not be provided or paid for by the Clinical Center, NIH.  
- Once you have completed taking part in the study, medical care will no longer be provided by the Clinical Center, NIH.
Clinical trial: NCT02298946
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation Cyclophosphamide (Ctx)|Risk Of Radiation|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

Specific symptoms that have been associated with cyclophosphamide as listed below. However, we will be using cyclophosphamide at a much lower doses at which the side effects listed are unlikely:  
- Changes in blood counts including: low red cell count (causing fatigue and shortness of breath), low platelet count (increasing the risk of bleeding and bruising), decrease in white blood cells (increasing the risk of infection and the need for treatment with antibiotics or other treatment)
- Loss of appetite, nausea, vomiting
- Diarrhea, stomach pain
- Mouth sores
- Hair loss
- Fatigue
- Muscle or joint aches
- Bladder damage which can cause blood in your urine

This research study involves exposure to radiation from stereotactic body radiation therapy and the CT used during your biopsies. Please note that this radiation exposure is not necessary for your medical care and is for research purposes only. The total amount of radiation you will receive in this study is from up to 3 treatments of stereotactic body radiation therapy and 2 CT guided biopsies. The NIH Radiation Safety Committee has reviewed the use of radiation in this research study and has approved this use as involving acceptable risk and necessary to obtain the research information desired. Using the standard way of describing radiation dose, from participating in this study, you will receive a total of 2400 rem to your gallbladder wall and liver and 600 rem to your adrenals. The total effective dose will be 309 rem. All other organs will receive smaller amounts of radiation. The amount of radiation received in this study exceeds the dose guideline established by the NIH Radiation Safety Committee for research subjects. The guideline is an effective dose of 5 rem (or 5,000 mrem) received per year. The specific side effects related to the effects of stereotactic body radiation therapy are described above.  
If you would like more information about radiation and examples of exposure levels from other sources, please ask the investigator for a copy of the pamphlet called, *An Introduction to* Radiation for NIH Research Subjects. Please tell your doctor if you have taken part in other research studies or received any medical care at the NIH or other places/hospitals that used radiation. This way we can make sure that you will not receive too much radiation. Consider 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. It is best to avoid radiation exposure to unborn or nursing children since they are more sensitive to radiation than adults.  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
STUDY NUMBER: 15-C-0021 CONTINUATION: page 10 of 15 pages

We hope that you will get personal medical benefit from taking part in this study, but we cannot be certain. 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: NCT02298946
Section: Procedures
Subsections: What Will Happen If You **Take Part In This Research Study?** Before You Begin The Study

Before you begin this study you will have several exams and tests to make sure you are eligible for this study. The exams and tests are part of regular cancer care and may be done even if you do not join the study. If you recently had some of the tests, they may not need to be repeated. The research team will explain these exams and tests to you. You will have:  
- History and physical exam
- Review of current medications and past treatments
- Routine blood work
- Viral blood tests  
PATIENT IDENTIFICATION CONTINUATION SHEET for **either:**  
NIH-2514-1 (07-09)  
NIH-2514-2 (10-84)  
P.A.: 09-25-0099  
File in Section 4: Protocol Consent  
STUDY NUMBER: 15-C-0021 CONTINUATION: page 3 of 15 pages  
- Routine urine tests
- Tumor measurements using special x-rays called computerized tomography (CT or CAT
scans) or magnetic resonance imaging (MRI) of your chest, stomach, and pelvis areas
- A heart test called an electrocardiogram or ECG to check your heart
- Urine or blood pregnancy test
Clinical trial: NCT02298946
Section: Purpose of Research
Subsections: Why Is This Study Being Done?|Why Are You Being Asked To Take Part In This Study?

Our immune system helps to protect us from germs and can also fight against cancer. T-cells are a type of white blood cell that can find and kill germs and tumors. T-cells are often present inside tumors, but cancers block the activity of these T-cells in many different ways. In tumors, some T-cells become dysfunctional, meaning that they are not able to kill tumor cells. These dysfunctional T-cells in the tumor make a protein called "PD-1" which they express on their surface. Some functional T-cells may also be present, but they are usually outnumbered.  
STUDY NUMBER: 15-C-0021 CONTINUATION: page 2 of 15 pages AMP-224 is an investigational drug that binds to the PD-1 on the surface of the T-cells. AMP224 therefore blocks the dysfunctional cells so that the functional cells can fight the tumor.  
"Investigational" means that AMP-224 has not been approved by the Food and Drug Administration (FDA) as either a prescription or over-the-counter drug. It has not been tested in combination with stereotactic body radiation therapy (SBRT), which is the main goal of this study. Stereotactic radiation treatment is a type of radiation therapy in which a few very high doses of radiation are delivered to small, well-defined tumors. The goal is to deliver a radiation dose that is high enough to kill the cancer while minimizing exposure to surrounding healthy organs. In this protocol SBRT is being used for research to see if tumor antigens will be released. This research is being done to study if the safety and effectiveness of the investigational drug AMP224 together with either 1 or 3 days of SBRT directed to the liver.  
This is the first study in which AMP-224 will be tested in combination with SBRT. In addition to the AMP-224 and radiation treatment you will also receive an additional small dose of chemotherapy drug called cyclophosphamide. Cyclophosphamide is a chemotherapy drug that has been shown to also have some immune effects at lower doses.

You have been invited to take part in this research study because you have been diagnosed with metastatic colorectal cancer that has spread to the liver and that has either not responded to prior treatment, or there are no curative treatment options available.
Clinical trial: NCT02298946
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 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
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. If you decide at any time to withdraw your consent to participate in the trial, we will not collect any additional medical information about you. However, according to FDA guidelines, information collected on you up to that point may still be provided to The Center for Cancer Research, Amplimmune, Inc. or designated representatives. If you withdraw your consent and leave the trial, any samples of yours that have been obtained for the study and stored at the NCI can be destroyed upon request. However, any samples and data generated from the samples STUDY NUMBER: 15-C-0021 CONTINUATION: page 12 of 15 pages that have already been distributed to other researchers or placed in the research databases cannot be recalled and destroyed.