ESR1 Peptide + GM-CSF Phase I Trial FAQ

What is the purpose of this study?

The purpose of this study is to find out what effects (good and bad) an investigational cancer vaccine, ESR1 peptides, in combination with GM-CSF and Montanide ISA, may have on your immune system’s activity and ability to control your cancer. The word “investigational” means that the vaccine is still being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA).
In ER-positive breast cancer (the type of breast cancer you have), the ER gene is over-active and produces extra ER protein. A gene contains information that determines in part the traits, such as eye color, height, or disease risk, that are passed on from parent to child. Genes do this by producing proteins. Proteins are the building blocks of your body, organs, and cells. In this case, the ER gene produces ER protein present on cancer cells. This research is designed to use the ER-overexpressing cancer cells as a target for a vaccine that will activate your immune system to fight the cancer cells.
The ESR1 peptide vaccine that will be studied in this research consists of five peptides that are fragments of the ER protein. Once these peptides are given to you as a vaccine, it can stimulate immune cells in your body. Your immune cells will react to the ESR1 peptides and activate other immune cells to tell them to attack cancer cells expressing ER.
This is the first study of ESR1 peptides in humans. The goal of this study is to find out if ESR1 peptides given in combination with GM-CSF and Montanide can cause an immune response against your cancer and whether it is safe.

How does this study work? What do patients receive?

The purpose of this research study is to find out if the investigational study vaccine, ESR1 peptides, are safe and has beneficial effects in people with Estrogen receptor positive (ER+) breast cancer.
If you decide to participate in this study, you will receive the ESR1 peptide vaccine in combination with GM-CSF (granulocyte-macrophage colony-stimulating factor) and Montanide, substances which enhance the body’s immune response. You will also be asked to:

 Return to the Duke Cancer Center for study visits 6-8 times over 10 weeks.
 Have blood drawn approximately 6 months, 1 year and 2 years after the injections.
 Be contacted by phone every 12 weeks to see how you are doing.
 Have a skin biopsy of your injection site for research purposes.

Who will be my doctor on this study?

If you decide to participate, Dr. Lyerly or one of the other oncologist investigators will be your doctor for the study and will be in contact with your regular health care provider throughout the time that you are in the study and afterwards, if needed.

Why is this study being done?

How many people will take part in this study?

Up to 40 people will take part in this study all at Duke.

What is involved in this study?

If you are eligible to participate in the study, you will be asked to return to the Duke Cancer Center for approximately 6-8 study visits over 10 weeks (about 2 months). The study will enroll people that have recurrent or metastatic breast cancer with no evidence of disease following previous therapies or surgery. People who have been stable on hormonal therapy for their cancer can continue this therapy during the trial. The study staff will schedule your visits with you and let you know when you will need to come back.

 Exams and Blood Tests: At each study visit, a medical history and a nurse assessment including vital signs will be performed. You may also have up to 90 mL of blood (6 tablespoons) drawn from a vein by needle stick, for routine tests such as blood count and chemistries, as well as for testing for research purposes only (tests to determine the response of your immune system).
o We will also review the results of your standard of care CT or MRI scans around the time of the last dose of study drug(s) and at 24 weeks after the initial dose to evaluate the extent of your cancer.
 Study Drug: You will receive a total of six injections of the ESR1 peptide cancer vaccine on weeks 0, 1, 2, 4, 5, 6.
o Each time you receive ESR1 peptide vaccine, you will be requested to remain at the hospital or clinic for one hour afterwards.
 Follow-up Visit: About 2 weeks after the last dose of study drug(s) you will return for a safety follow-up visit where we will ask you how you are feeling and if you are experiencing any ongoing issues. You will have a physical exam and we will also take blood for routine testing and up to 90mL of blood for research purposes.
o Skin Biopsy: you will be asked to have two 3-5 mm punch biopsies of the skin to collect samples of your ESR1 peptides injection site and a normal patch of skin for research purposes. This is optional. Please indicate if you agree to have skin biopsy(s) taken for research.

 Long-term Follow-up: After 8 weeks, you will enter the follow-up phase of the study. We will also ask you to participate in the follow-up phase if you leave the study early. The follow-up phase will consist of a review of the following:
o A review of your medical record by our study team,
o Contact by a member of our study team by phone, email or in person (if you come for a clinic visit) approximately every 12 weeks for one year to inquire about your health and any problems you have had since receiving the study drug(s).
o You will also have up to 90 mL of blood (6 tablespoons) drawn from a vein by needle stick for research purposes only (tests to determine the response of your immune system) at 24 weeks (approximately 6 months) and 48 weeks (approximately 1 year)
o We will contact you once more a year later (approximately 2 years after the last vaccine injection) to see how you are doing and ask for you to have up to 90 mL of blood (6 tablespoons) drawn from a vein by needle stick for research purposes only (tests to determine the response of your immune system).

Future Research and Genetic Testing
There may be blood and/or tissue samples left over from this study. We would like to save these samples to be used for research purposes that are not specifically related to this study. You do not have to allow the use of your samples for future research to participate in this study. If you do not wish to have your samples used in the future, they will be destroyed at the end of this study. If you agree to allow your specimens to be used for future research, the information may be used to study changes in genetic material (DNA) that is passed on in families, or that is influenced by environment and lifestyle. The results can then be studied to identify changes in DNA that may result in the development of diseases or the effectiveness of specific treatments. Genetic studies are for research purposes only.

Potential Risks and the Genetic Information Non-Discrimination Act (GINA):
There is a potential risk of loss of confidentiality. Every effort will be made to protect your confidential information, but this cannot be guaranteed. The genetic information obtained as a result of your participation in this research will not be included in your medical record. Information from which you may be personally identified will be maintained in a confidential, secure location at DUHS, accessible only by authorized members of the study team, and will not be disclosed to third parties except as described in this consent form, with your permission, or as may be required by law.

The Genetic Information Nondiscrimination Act (GINA) is a Federal law that will protect you in the following ways:

 Health insurance companies and group plans may not request genetic information from this research
 Health insurance companies and group plans may not use your genetic information when making decisions regarding your eligibility or premiums

How long will I be in this study?

You will be in the study drug phase of the study until 8 weeks from the first administration of the study drug. At that time, you will then continue into the follow-up phase of the study. The follow-up phase, as described above, will continue for two years.
You can choose to stop participating at any time without penalty or loss of any benefits to which you are entitled. However, if you decide to stop participating in the study, we encourage you to talk to your doctor first.

Can I continue to take my medications?

To participate in this study you may need to stop or change some of your current medications because they may affect how well the study drugs work. However, this is unlikely. You will be notified if any of your current medications need to be stopped or changed to allow you to participate in this study. If there are any changes, your doctor will let you know of any risks that may be associated with changes in your current medications. If you participate in this study, there may also be limitations to the other medications and supplements or foods that you can take while you are taking the study drug. Changing or limiting the medications you take for other conditions may be associated with additional inconvenience, costs, and/or side effects.

What are the risks of the study?

This is the first time ESR1 peptide vaccine has been given to humans. While on this study, you are at risk for side effects below and possibly others. There may be other side effects not listed that the researchers cannot predict. You should discuss these with your doctor.

he ESR1 Peptide Vaccine consists of ESR1 peptides, GM-CSF, and Montanide. The possible side effects for each are described.
ESR1 Peptide Risks
ESR1 Peptides may cause some, all or none of the side effects listed below.

 Fever
 Chills
 Headache
 Injection site reactions

Allergic reactions with swelling in such places as your throat or lungs.

Medications that might be needed to treat allergic reactions include antihistamines such as diphenhydramine (Benadryl), epinephrine and corticosteroids. Other medications may be given to make side effects less serious and uncomfortable.

Risks using Montanide and GM-CSF are well documented and included in our consent form

Additional Study Drug Risks:

Your immune system could be stimulated to attack your own body (called autoimmunity), causing a low white blood cell count, which could lead to developing an infection, skin rash, joint swelling, intestinal inflammation (chronic colitis), or fluid around the heart and lungs.
Because this is the first time ESR1 peptide vaccine has been given to humans, there may be risks, discomforts, drug interactions or side effects that are not yet known.
Some side effects may occur that do not need medical attention and may go away as your body adjusts. Others may be severe and need immediate attention or lead to hospitalization. Seek emergency care and contact your doctor immediately if severe side effects occur.
Administration of ESR1 peptide vaccine with any other breast cancer therapies is investigational and the possible risks and side effects of combining the study drug with these therapies are unknown.
Your doctor will discuss with you the risks of the specific breast cancer therapy you receive. You should inform your doctor immediately of any side effects you experience.

What benefits are there to being in this study?

If you agree to take part in this study, there may be direct medical benefit to you. If the study drug(s) work for you, you may have better control of your cancer, which may extend your life, however this cannot be guaranteed. We hope the information learned from this study will benefit other people with cancer in the future.

Will my information be kept confidential?

Participation in research involves some loss of privacy. We will do our best to make sure that information about you is kept confidential, but we cannot guarantee total confidentiality. Your personal information may be viewed by individuals involved in this research and may be seen by people including those collaborating, funding, and regulating the study. We will share only the minimum necessary information in order to conduct the research. Your personal information may also be given out if required by law.
As part of the study, results of your study-related laboratory tests, scans, and procedures may be reviewed in order to meet federal or state regulations. Reviewers may include representatives from the Food and Drug Administration, the Duke University Health System Institutional Review Board, Duke Cancer Institute, Duke Office of Audit, Risk and Compliance and others as appropriate. If any of these groups review your research record, they may also need to review your entire medical record.
As part of this study, you will be asked to have certain tests and/or procedures performed. Some of these tests and/or procedures would have been done as part of your regular care. The study doctor will use these test results both to treat you and to complete this research. These test results will be recorded in your medical record and will be reported to the research data office at Duke. Results of tests and studies done solely for this research study and not as part of your regular care will also be included in your medical record.

As part of this protocol, you will be tested for HIV (human immunodeficiency virus, which is the virus that causes the acquired immunodeficiency syndrome [AIDS]) and Hepatitis B and C antigens. You will be notified of the results of the testing, and counseled as to the meaning of the results, whether they are positive or negative. If the test indicates that you are infected with HIV or Hepatitis B or C, you will receive additional counseling about the significance of your care and possible risks to other people. We are required to report all positive results to the North Carolina Division of Public Health. The test results will be kept confidential to the extent permissible under the law. If you do not want to be tested for HIV or Hepatitis, then you should not agree to participate in this study.
The study results will be retained in your research record for at least six years after the study is completed. At that time, either the research information not already in your medical record may be destroyed or information identifying you will be removed from study results at DUHS. Any research information in your medical record will be kept indefinitely.
While the information and data resulting from this study may be presented at scientific meetings or published in a scientific journal, your name or other personal information will not be revealed.
Some people or groups who receive your health information might not have to follow the same privacy rules. Once your information is shared outside of DUHS, we cannot guarantee that it will remain private. If you decide to share private information with anyone not involved in the study, the federal law designed to protect your health information privacy may no longer apply to the information you have shared. Other laws may or may not protect sharing of private health information.

Will participating in this study cost me anything?

No. You or your insurance provider will be responsible and billed for all costs related to your routine medical care, including copayments and deductibles. Routine medical care services are those that you would have received for your condition if you were not participating in this research study. Not all services are covered by insurance. Some procedures or scans may require pre-authorization by your insurance plan. We will notify you if we learn that a service is not covered by your insurance plan as part of the pre-authorization process. If it is not covered, you will be responsible for paying for it. The amount of your out-of-pocket expense will depend on your insurance plan. For beneficiaries with Medicare Advantage Plans, traditional Medicare is billed for the routine cost of a research study. You may have more or higher co-pays than with a Medicare Advantage plan. Please discuss the costs of the study with Dr Lyerly. At your request, a Financial Counselor in the clinic may provide you with an estimate of costs for routine services.
The study will pay for services and procedures that are done solely for research purposes, including providing the ESR1 peptide vaccine, lab tests that are not standard of care, and the research biopsies that are not performed for standard of care. Please talk with the PI/study team about the specific services and procedures that will be paid for, and the ones for which you or your insurance will be responsible.