Clinical trial: NCT02520063
Section: Alternatives
Subsections: Alternative Treatments And Procedures

Taking part in this research study is voluntary. Instead of being in this research study, you have other options, which may include the following:  
1. Participate in another research study. 2. Other treatment including chemotherapy or letrozole alone.
You may choose not to have treatment for cancer at all. Please talk to the research doctor about your options before you decide whether you will take part in this research study.
Clinical trial: NCT02520063
Section: Confidentiality
Subsections: Confidentiality

Records of your participation in this study will be kept confidential to the extent permitted by law. However, your doctor and his/her staff, representatives of the drug manufacturers (NOVARTIS and TRACON Pharmaceuticals) and its authorized agents, the U.S. Food and Drug Administration (FDA), and the UAB Institutional Review Board (IRB) will be able to inspect your records and have access to confidential information which identifies you by name. The results of the treatment may be published for scientific purposes. These results could include your lab tests and X-rays; however, your identity will not be given out. Any publication of the data will not identify you by name. If any part of this study takes place at University of Alabama Hospital this consent document will be placed in your file at that facility. The document will become part of your medical record chart. In addition, information from your medical records can be reviewed by foreign regulatory agencies (similar to the U.S. Food and Drug Administration) as provided in the International Conference on Harmonization - Good Clinical Practice Guidelines. These agencies may include the European Commission and Japanese Ministry of Health and Welfare. A complete list of the agencies may be obtained by calling the UAB IRB office at 205-934-3789. Should your medical record need to be reviewed by a foreign regulatory agency, a member of the IRB staff will observe the review of your medical record so that the record is not removed, copied or identifiable information recorded in any manner. By signing this document, you agree to allow access as described above to your records even if you withdraw from the study. Information relating to this study, including your name, medical record number, date of birth and social security number may be shared with the billing offices of UAB and UAB Health Systemaffiliated entities so that claims may be appropriately submitted to the study sponsor or to your insurance company for clinical services and procedures provided to you during the course of this study. A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time. If you receive services in University Hospital as part of this trial, this informed consent document will be placed in and made part of your permanent medical record at this facility.
Clinical trial: NCT02520063
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Possible Risks And Discomforts

You may have some side effects from taking these drugs. During the study, you must talk to the study doctor before you take any drug other than the study drug. This includes homeopathic, alternative, or herbal medicines and vitamins. Please avoid eating grapefruit, star fruit, and Seville oranges or drinking their juices while in the study. The juices in these fruits can change the way your body treats or breaks down the study drug. Many side effects go away shortly after the study drug is stopped. In some cases, the side effects may be serious, last a long time, or be permanent, and may even cause death. This research study may involve unknown risks. Problems or side effects that are not now known could also occur. All problems or side effects need to be reported to the study doctors or study nurses looking after you either by phone or at the next visit. For more information about risks and side effects, you should feel free to ask your study doctor. If you are concerned about your health between visits due to being in this study, please call your doctor or the study nurse at the telephone numbers provided at the end of this document. The most common, and frequently seen, side effects of letrozole include hot flashes, joint pain and stiffness, night sweats, nausea, fatigue, muscle pains, and swelling. Everolimus can cause the following side effects: weakness, chills, vomiting, weight loss, pain or swelling of the arms or legs, bleeding of the nose, cough, abnormal or loss of taste, spontaneous bleeding or bruising, dry mouth, dehydration, skin changes (acne, rash, redness, dryness or irritation, itching and skin inflammation), abdominal pain, stomach virus, passing gas, constipation, irritability, nail disorders, increased blood pressure, joint stiffness or pain, difficulty swallowing, heartburn, fever, insomnia, inflammation of the lining of the digestive system and other mucous membranes, lowering of hemoglobin in your blood which could lead to anemia, rash of small blisters, bronchitis, coughing up of blood, swelling of the dermis, congestive heart failure, chest pain unrelated to the heart, impaired wound healing, daytime urination, feeling tired, loss of appetite, headache, diarrhea, nausea, itching, shortness of breath and very rarely inflammation in the lungs which in most cases resolves once the drug is held. The most frequent side effect with everolimus is irritation and inflammation in the mouth. It is seen in about 40% of patients and can be severe in about 20-25% of patients. About 20% of patients may develop a skin rash; itching has been seen in about 13% of patients. Shortness of breath has been seen in about 7% of patients. You should be aware as well, that everolimus weakens the ability of your body to fight infections so you are at risk for infections. If you are at risk for hepatitis, you will be tested before starting the drug. Hepatitis can be silent and not cause symptoms. If you are found to have hepatitis, you will not be allowed into the study. The most frequently observed laboratory abnormalities include: decrease of the number of normal blood cells (red and white blood cells and platelets); increase cholesterol, triglycerides, glucose (which could lead to diabetes), liver function tests (aspartate transaminases, alanine transaminases, and bilirubin), renal functions tests (creatinine); and decrease of phosphate and potassium. You should not receive live vaccines and have close contact with people who have received live vaccines within 7 days of starting everolimus and while on this study without consultation with your study doctor. The most common side effects with TRC105 are allergic reactions with the infusion of the drug, mild bleeding (nose bleeds and blood spots in the skin), headaches, and anemia. In addition, nasal stuffiness, swelling around the eyes, and skin rash have also been observed. To decrease the possibility for an allergic reaction with TRC105, you will receive drugs before the infusion, and, if necessary, we will administer the drug over a longer period of time (4 hours for the first two times). If there are no reactions, we will administer the drug over progressively shorter periods of time. Headache is usually seen with the first infusions of the drug. The headache is usually throbbing and responds to common painkillers as well as drugs for migraines. To avoid headaches, we will split the first dose of the drug to be given in two separate days (days 1 and 4) rather than give it to you over one day. Risks associated with tumor biopsies include and are not limited to: 1. Pain and discomfort. The amount of pain and discomfort will vary, depending on the location of the biopsy site. These risks can be discussed with the study doctor.  
2. Minor bleeding at the biopsy site. 3. Tenderness at the biopsy site. 4. Scarring at the biopsy site. 5. Rarely, an infection at the biopsy site. 6. Uncommonly, complications from biopsies can be life threatening. As with any interventional procedure, other potentially serious complications from bleeding or organ damage may occur. These might require additional surgical intervention.  
When having an MRI (Magnetic Resonance Imaging) scan, you will lie still on a table that slides into a tunnel slightly wider than your body. People who feel uncomfortable in confined spaces (claustrophobia) may feel uncomfortable in the narrow cylinder. If you feel uncomfortable in confined spaces, please tell your doctor. Your doctor may give you a medication to make you feel more comfortable in a confined space. MRIs use powerful magnets to make images. Therefore, persons with certain metal implants, such as pacemakers should not have an MRI. (If you have an implant or any metal in your body, please check with your study care doctor to know whether you can have an MRI or not.) For people without metal implants, there are no known health risks associated with exposure to the magnet. As images are taken, a loud banging noise will be produced. Earplugs or headphones will be available if needed. The MRI can be stopped at any time at your request, but the scan may not be complete. During your treatment, you will undergo blood draws every 4 weeks. Potential risks of blood drawing include pain for the needle being inserted through the skin into the vein, bruising, clot formation under the skin, lightheadedness, possible fainting, and rarely, infection. You should also be aware that because of side effects or the time required for tests and clinic visits while you are on this research study, you may be unable to keep up with your normal daily activities.
Clinical trial: NCT02520063
Section: Procedures
Subsections: Procedures

If you give your consent for this study by signing this form, certain tests will be performed to see if you can participate (inclusion criteria). The study consists of the following parts: a screening period, a treatment period that will last up to 24 weeks, and a follow-up period. The maximum time of study participation is 24 weeks. Additionally, basic information concerning your condition will be collected following the study period. Before receiving letrozole, everolimus, and TRC105, you will undergo a screening process that involves the following: a medical history, a complete physical examination including vital signs (blood pressure, pulse, temperature, weight, respirations, and height), mammogram, ultrasound of the breast with and without contrast media, CT scans or MRI of your body if indicated, baseline measurement of heart function if it has not been tested in the past 3 months and you have a history of heart disease, laboratory blood (approximately 3-4 tablespoons) and urine tests. We will also perform a breast MRI (magnetic resonance imaging: take pictures of your breasts using a large magnet similar to a CT scan but without the radiation) and a breast ultrasound. Breast ultrasound does not involve radiation. If a sample of your tumor has not been frozen immediately after the biopsy, a new sample of the tumor will be taken (biopsy) for research purposes only. The tumor sample will be obtained by the surgeon or the mammographer. After completing the screening process, your physician will determine whether you are still eligible for participation in the study. If you are eligible and still wish to participate, a number will be assigned to you. As part of the study we are looking for changes in the characteristics of the tumor in response to therapy. Therefore, as part of the study we ask that you undergo a biopsy of the breast tumor (core needle biopsy) after 4 weeks of treatment. A biopsy of your normal breast tissue may be obtained if you consent to the procedure (optional). The tumor sample will be obtained by the surgeon or the mammographer. The area of the breast that is to be sampled will be cleaned and numbed with local anesthetic.
Clinical trial: NCT02520063
Section: Withdrawal from Study
Subsections: Participant **Withdrawal**

Whether or not you take part in this study is your choice. There will be no penalty if you decide not to be in the study. If you decide not to be in the study, you will not lose any benefits you are otherwise owed. You are free to withdraw from this research study at any time. Your choice to leave the study will not affect your relationship with this institution. However, you should return to see the study doctor for safety reasons so you can be taken off the study drug and referred, if necessary, for follow-up care. When you return to see the doctor, the doctor will examine you and assess possible side effects associated with the study drugs. You will also undergo bloodwork and your urine will be tested. The doctor may ask you to come back if there are ongoing side effects related to the study drugs. You may be removed from the study without your consent if the sponsor ends the study, if the study doctor decides it is not in the best interest of your health, or if you are not following the study rules. Other reasons for which the doctor may take you off the study include severe side effects, growth of the tumor despite treatment, or if the need arises for drugs or treatment such as surgery or radiation therapy that is not allowed by the study. If you are a UAB student or employee, taking part in this research is not a part of your UAB class work or duties. You can refuse to enroll, or withdraw after enrolling at any time before the study is over, with no effect on your class standing, grades, or job at UAB. You will not be offered or receive any special consideration if you take part in this research.