Clinical trial: NCT02179515
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  
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: 14-C-0142 CONTINUATION: page 9 of 13 pages  
- 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: NCT02179515
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
- Qualified representatives from Bavarian Nordic, Inc, the pharmaceutical company who produces MVA-brachyury-TRICOM.  
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: 14-C-0142 CONTINUATION: page 10 of 13 pages  
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 collaborators or designated representatives. If you withdraw your consent and leave the trial, any samples of yours that have been obtained for the study and stored at the NCI can be destroyed upon request. However, any samples and data generated from the samples that have already been distributed to other researchers or placed in the research databases cannot be recalled and destroyed.
Clinical trial: NCT02179515
Section: Duration of Study Involvement
Subsections: During The Study|How Long Will I Receive Vaccines?|When You Are Finished Getting The Vaccine (Treatment)|Long Term Follow Up

If the initial exams and tests show that you can participate in this study, you will come to the NIH about every four (4) weeks for MVA-brachyury-TRICOM vaccines, exams and tests, for periodic visits. Depending into which dose level you enroll, the MVA-brachyury-TRICOM vaccine will be given as 1, 2 or 4 small shots (injections), depending on which dose level you enroll into, under the skin into sites were of your body known to drain into a large number of lymph nodes. Lymph nodes contain large numbers of immune cells, which can potentially be activated (or turned on) by the vaccine to target cancer cells. In general, these sites will include upper thighs and the area around the armpits. The site may be dependent on the number of injections needed for each dose or other individual factors related to your body.  
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: 14-C-0142 CONTINUATION: page 4 of 13 pages The following tests and procedures will be done during the time you are on this study. Many of them are part of regular cancer care; however, some tests and procedures may be done more often because you are on this study.  
- Clinic visit **(physical exam):** we will ask you how you are feeling and do a physical examination. This exam will be done every 4 weeks if you are not having any problems.  
- **Vital signs:** we will measure your blood pressure, temperature, pulse, breathing and weight each time you come to the clinic.  
- **Routine blood tests:** lab tests of your organ functions (liver, kidneys, blood clotting, red and white blood cells, platelets, blood sugar and blood electrolytes) will be tested each time you come to clinic. In addition, there are some brachyury cells in the thyroid, so we will test your thyroid function at regular intervals to make sure the vaccine is not harming the thyroid gland
- **Urine test**: you will be asked to give a urine sample for testing each time you come for an outpatient visit.  
- **CT scans or MRI** that detect the size of your tumor will be done at baseline (beginning therapy), after 3 months on study, and again 3 months later if you remain on study to that point. This is done so that any benefit of the vaccine can be determined or if your cancer is not responding to the vaccine, the study team can tell you and help you to seek other treatment options.  
- ECG: this will be done to check your heart rhythm at 2-4 time points - once before starting vaccine and at the time of your last scheduled vaccine and on your final followup visit.
Research Blood Samples: It is important to understand the effects of this experimental vaccine on your body, particularly the immune system. To do this, blood samples (8 tubes of blood or about 5 tablespoons) will be taken at specific time points during your participation in this study.

You will receive MVA-brachyury-TRICOM vaccines every 4 weeks (or every 28 days) for 3 doses, as long as you do not have unacceptable side effects, your cancer does not get worse, and you are willing to continue participating. You will have follow-up visits for imaging and research blood draws at three months after enrollment and every three months until there is evidence of disease growth.

When you stop the MVA-brachyury-TRICOM vaccine, we will ask you to return to NIH for clinic visits at least every 3 months until you recover from any side effects and/or your cancer  
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: 14-C-0142 CONTINUATION: page 5 of 13 pages worsens. At these visits you will have exams, tests and procedures that are part of regular cancer care, including physical exam, standard blood tests, scans and x-rays.

At the end of this study, we would like to follow you for any late side effects, and see how you do on other treatments. We will request that at that time you enroll on our Long Term FollowUp Study, 04-C-0274, which the study team will review with you.
Clinical trial: NCT02179515
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.  
- 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: NCT02179515
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Risks Or Discomforts Of Participation What Side Effects Or Risks Can I Expect **From Being In This Study?**|Other Risks And Side Effects Related To Research Procedures:|Gene Therapy Risk Of Cancer **And Other Diseases**|Potential Benefits Of Participation Are There Benefits To Taking Part In This Study?

You may have side effects while on the study. Everyone taking part in the study will be watched carefully for any side effects. However, doctors don't know all the side effects that may happen when taking the MVA-brachyury-TRICOM vaccine, so it is important to report changes that you notice, even if your study team does not ask you specifically about them. It is very important that you tell a member of the research team before starting any new medications. We do not know what side effects could happen when other drugs are given with the MVA-brachyuryTRICOM vaccine.  
Side effects to the vaccine may be mild or very serious. Your health care team may give you medicines to help lessen side effects. Many side effects go away with those medicines, and others can go away soon after you stop receiving the vaccine. In some cases, side effects can be serious, long lasting, or may never go away, and may result in death. You should talk to your study team about all symptoms that you experience while taking part in the study.  
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: 14-C-0142 CONTINUATION: page 7 of 13 pages  
| Likely   | Less Likely                                                                                                                  | Rare but Serious   |                      |
|----------|------------------------------------------------------------------------------------------------------------------------------|--------------------|----------------------|
| -        | Injection site reaction  (including pain or  discomfort, itching,  redness, firmness,  swelling, skin  thickening, or bumps) | -                  | Acute fever          |
| -        | Chills                                                                                                                       |                    |                      |
| -        | Flu-like symptoms (including  fatigue, soreness, general body  pain, abdominal pain, cough,  fever, headache)                |                    |                      |
| -        | Chest tightness                                                                                                              |                    |                      |
| -        | Shortness of breath                                                                                                          |                    |                      |
| -        | Leg pain and / or swelling                                                                                                   |                    |                      |
| -        | Headache                                                                                                                     |                    |                      |
| -        | Loss of appetite                                                                                                             |                    |                      |
| -        | Weight loss                                                                                                                  |                    |                      |
| -        | Diarrhea                                                                                                                     |                    |                      |
| -        | Constipation                                                                                                                 |                    |                      |
| -        | Rash                                                                                                                         |                    |                      |
| -        | Nausea                                                                                                                       |                    |                      |
| -        | Dizziness                                                                                                                    |                    |                      |
| -        | Mild inflammation of the tissue  lining the lung                                                                             |                    |                      |
| -        | Chronic inflammation of the  skin                                                                                            |                    |                      |
| -        | Insomnia                                                                                                                     |                    |                      |
| -        | Open sores at the injection site  (ulceration)                                                                               |                    |                      |
| -        | Enlargement of the lymph  nodes                                                                                              |                    |                      |
| -        | Low blood levels of sodium                                                                                                   |                    |                      |
| -        | Inflammation of the testicles (in  men)                                                                                      |                    |                      |
| -        | Inflammation of thyroid tissue,  causing changes in thyroid  function test results                                           | -                  | Difficulty breathing |
| -        | Low blood pressure                                                                                                           |                    |                      |
| -        | Wheezing                                                                                                                     |                    |                      |
| -        | Clots in the lung                                                                                                            |                    |                      |
| -        | Clots in the leg                                                                                                             |                    |                      |
| -        | Kidney damage                                                                                                                |                    |                      |
| -        | Decreased oxygen levels  in the blood                                                                                        |                    |                      |
| -        | Fluid around the lining  of the lungs                                                                                        |                    |                      |
| -        | Fluid around the lining  of the heart                                                                                        |                    |                      |  
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: 14-C-0142 CONTINUATION: page 8 of 13 pages

Blood Sampling: Bruising or bleeding at the needle site; rarely infection. This is treated with bandages, pressure and, if infection, antibiotic medicines.  
Risks of blood draws: Blood samples will be drawn from a vein in your inner arm. The risk of a blood draw may include fainting or pain. There could be bruising or infection at the site where blood is drawn. The risk is no greater than if you were having blood drawn for routine and normal healthcare.  
Risks from X-rays and / or Scans: The risks of the contrast material used with the CT scan include rare allergic reactions, nausea, flushing, low blood pressure, asthma, stroke and organ damage. If the contrast material is given via your vein, it may make you feel flushed and give you a sensation of "pins and needles" for a few seconds.

We are unsure if this type of gene therapy will cause you to become sick in the future. It is possible that it may cause your immune system or nerves not to work well or cause a sickness of your blood cells or even a cancer (for example leukemia). We do not know if you will develop any of these disorders, but you need to be aware of this possible risk. Children in France and England received gene therapy for a particular disease of the immune system. Most of the children were cured but 5 children out of 22 later developed leukemia and one died. Experts who looked at these cases thought that the gene therapy caused the leukemia in these children. To watch you for this risk we will be testing your blood as described before.

The purpose of this study is to test the safety of the experimental vaccine MVA-brachyuryTRICOM, and to test whether it stimulates your immune system. Taking part in this study may or may not make your health better. 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: NCT02179515
Section: Procedures
Subsections: Description Of Research Study What Will Happen If You **Take Part In This Research Study?** Before You Begin The Study:

You will need to have the following exams, tests and procedures if you can be in the study. These exams, tests and procedures are part of regular cancer care and may be done even if you do not join the study. If you have had some of them done recently, they may not need to be repeated. This will be up to the study team.  
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: 14-C-0142 CONTINUATION: page 3 of 13 pages  
- A complete medical history, including your cancer history and prior cancer treatments, all drugs that you may be taking, including over the counter drugs, vitamins and herbal supplements.  
- Pathology review of your tumor sample.  
- A complete physical examination, including assessing your ability to do physical activities and measuring your blood pressure, heart rate and breathing.  
- Standard blood and urine tests to evaluate your organs' functioning (such as liver, kidneys, thyroid, blood sugar and blood electrolytes), including tests of your immune system and presence of infections.  
- Evaluation of your cancer, which may include a CT (computed tomography) scan, a PET
(positron emission tomography) scan, Bone scan and/or a Brain MRI (magnetic resonance imaging).  
- A 12 lead ECG (electrocardiogram) to assess your heart.  
- As part of this study, we will test you for infection with the human immunodeficiency virus (HIV), the virus that causes AIDS. If you are infected with HIV you will not be able to participate in this study because this cancer drug relies on the immune system to work. We will tell you what the results mean, how to find care, how to avoid infecting others, how we report newly diagnosed HIV infection, and the importance of informing your partners at possible risk because of your HIV infection.  
- A pregnancy test will be performed in women who are able to have children. Women who are pregnant or breast-feeding will not be allowed to participate, as the effects of vaccine on a developing fetus or infant are not known.  
- HLA typing: this blood test is done to see what protein is expressed by your blood cells, human leukocyte antigen (HLA).
Clinical trial: NCT02179515
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

The NIH research team is studying an experimental vaccine made with yeast and designed to target cells expressing the brachyury protein. Brachyury is a 'transcription factor' within the T gene that regulates making proteins. Research shows that in some cancers, such as gastrointestinal, bladder, kidney, ovary, uterus and testicular cancers, brachyury is 'over expressed' and is thought to play a role in cancer growth and metastasis.  
  
STUDY NUMBER: 14-C-0142 CONTINUATION: page 2 of 13 pages The vaccine is made with modified vaccinia Ankara (MVA) virus. This is a replication-deficient, attenuated derivative of vaccinia. The virus is genetically modified, made to express the brachyury protein, and deliver a combination of three human T-cell costimulatory molecules that stimulate the immune system, called TRICOM (B7.1, ICAM-1 and LFA-3). The goal is to "teach" the immune system to kill the tumor cells that express the brachyury protein, to help stop tumor cell growth and metastasis. This study will test the safety of giving the MVA-brachyury-TRICOM vaccine to people with cancer. The vaccine is manufactured by Bavarian Nordic, Inc. and is known as MVAbrachyury-TRICOM. In previous studies, similar vaccines were found to be safe, well-tolerated, and had few side effects.
Clinical trial: NCT02179515
Section: Voluntary Participation
Subsections: Why Are You Being Asked To Take Part In This Study?

You are being asked to participate in this study because standard therapies have not been effective for your type of cancer and we are testing possible new agents for safety and to see if they are effective. Your participation is entirely voluntary.