Clinical trial: NCT03329378
Section: Alternatives
Subsections: Other Possible Options To Consider:

You may decide not to take part in this research study without any penalty. The choice is totally up to you.  
If you choose not to participate in this research study, you will continue to receive treatments and diagnostic procedures including radiographic imaging, and blood tests for your cancer that are standard of care and appropriate as determined by your medical oncologist and could potentially include either one of these treatment regimens.
Clinical trial: NCT03329378
Section: Confidentiality
Subsections: Maintaining Confidentiality - Hipaa Authorization:|Why Is Your Protected Health Information Being Used?|Who, Outside Mount Sinai, Might Receive Your Protected Health Information?|Notice Concerning Hiv-Related Information

As you take part in this research project it will be necessary for the research team and others to use and share some of your private protected health information. Consistent with the federal Health Insurance Portability and Accountability Act (HIPAA), we are asking your permission to receive, use and share that information.  
What protected health information is collected and used in this study, and might also be disclosed (shared) with others? As part of this research project, the research team at the hospital(s) involved in the research will collect your: name, address, telephone, dates directly related to the individual (birth, admission, discharge, etc.), social security number, medical records number, health plan numbers, , and other unique numbers] The researchers will also get information from your medical record at the Mount Sinai Health System and your private doctor. During the study the researchers will gather information by:  
taking a medical history (includes current and past medications or therapies, illnesses, conditions or symptoms, family medical history, allergies, etc.)
doing a physical examination that generally also includes blood pressure reading, heart rate, breathing rate and temperature completing the tests, procedures, questionnaires and interviews explained in the description section of this consent.

Your personal contact information is important to be able to contact you during the study. Your health information and the results of any tests and procedures being collected as part of this research study will be used for the purpose of this study as explained earlier in this consent form. The results of this study could be published or presented at scientific meetings, lectures, or other events, but would not include any information that would let others know who you are, unless you give separate permission to do so. The Principal Investigator may also use and share the results of these tests and procedures to treat you in collaboration with others in the Mount Sinai Health System. The research team and other authorized members of The Mount Sinai Health System ("Mount Sinai") workforce may use and share your information to ensure that the research meets legal, institutional or accreditation requirements. For example, the School's Program for the Protection of Human Subjects is responsible for overseeing research on human subjects, and may need to see your information. If
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you receive any payments for taking part in this study, the Mount Sinai Finance Department may need your name, address, social security number, payment amount, and related information for tax reporting purposes. If the research team uncovers abuse, neglect, or reportable diseases, this information may be disclosed to appropriate authorities.

As part of the study, the Principal Investigator, study team and others in the Mount Sinai workforce may disclose your protected health information, including the results of the research study tests and procedures, to the following people or organizations: (It is possible that there may be changes to the list during this research study; you may request an up-to-date list at any time by contacting the Principal Investigator).  
- Other collaborating research center(s) and their associated research/clinical staff who are working with the investigators on this project: the Mount Sinai Hospital, Mount Sinai Beth Israel, Mouth Sinai West.
- Research data coordinating office and/or their representative(s) who will be responsible for collecting results and findings from all the centers: the Mount Sinai Hospital.  
- A Data Safety Monitoring Board or other committee that will monitor the study on an ongoing basis for safety.  
- The United States Food and Drug Administration.  
- The United States Department of Health and Human Services and the Office of Human Research Protection.
In all disclosures outside of Mount Sinai, you will not be identified by name, social security number, address, telephone number, or any other direct personal identifier unless disclosure of the direct identifier is required by law. Some records and information disclosed may be identified with a unique code number. The Principal Investigator will ensure that the key to the code will be kept in a locked file, or will be securely stored electronically. The code will not be used to link the information back to you without your permission, unless the law requires it, or rarely if the Institutional Review Board allows it after determining that there would be minimal risk to your privacy. It is possible that a sponsor or their representatives, a data coordinating office, a contract research organization, may come to inspect your records. Even if those records are identifiable when inspected, the information leaving the institution will be stripped of direct identifiers. Additionally, when applicable, the monitors, auditors, the IRB, the Office of Human Subjects Protection (OHRP) of the Department of Health and Human Services as well as the Food and Drug Administration (FDA) will be granted direct access to your medical records for verification of the research procedures and data. OHRP and FDA are authorized to remove information with identifiers if necessary to complete their task. By signing this document you are authorizing this access. We may publish the results of this research. However, we will keep your name and other identifying information confidential. For how long will Mount Sinai be able to use or disclose your protected health information? Your authorization for use of your protected health information for this specific study does not expire.  
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If you are authorizing the release of HIV-related information, you should be aware that the recipient(s) is (are) prohibited from re-disclosing any HIV-related information without your authorization unless permitted to do so under federal or state law. You also have a right to request a list of people who may receive or use your HIV-related information without authorization. If you experience discrimination because of the  
  
Study ID \#: IRB-17-02073 **Form Version Date: 8.23.2019**
release or disclosure of HIV-related information, you may contact the New York State Division of Human Rights at (888) 392-3644 or the New York City Commission on Human Rights at (212) 306-5070. These agencies are responsible for protecting your rights.  
Signature Block for Capable Adult Your signature below documents your permission to take part in this research and to the use and disclosure of your protected health information. A signed and dated copy will be given to you.  
| Signature of subject    | Date   |
|-------------------------|--------|
| Printed name of subject | Time   |
Clinical trial: NCT03329378
Section: Duration of Study Involvement
Subsections: Funds For Conducting This Research Are Provided By Mount Sinai. Length Of Time And Number Of People Expected To Participate

Your participation in this research study is expected to last 3 years (1 year on study, 2 years of cardiac follow-up). The study will take place in the Dubin Breast Center at Mount Sinai Hospital, Mount Sinai Beth Israel Comprehensive Cancer Center West, and Mount Sinai West. The number of people expected to take part in this research study at MSH (Mount Sinai Hospital) is 45 patients, 18 patients at MSBI (Mount Sinai Beth Israel), and 12 patients at MSW (Mount Sinai West). The total number of people expected to take part in this research study is 75.
Clinical trial: NCT03329378
Section: Participant Responsibilities
Subsections: Your Responsibilities If You Take Part In This Research:

If you decide to take part in this research study you will be responsible for the following things:
Attending study visits as specified Following the instructions of the study team Using effective birth control Informing the study team of new medications prescribed by any of your health providers before starting chemotherapy Informing the study team of any side effects you may experience.
Clinical trial: NCT03329378
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: You Will Not Be Paid For Taking Part In This Study. Possible Benefits:|Reasonably Foreseeable Risks And Discomforts: Trastuzumab And Pertuzumab|More Likely >10%|Very Unlikely<1%|Doxorubicin|Less Likely 1% To 10%|Cyclophosphamide|Paclitaxel|Blood Draw Risks|Fertility/Pregnancy Risks

It is important to know that you may not get any benefit from taking part in this research. Others may not benefit either. However, possible benefits may be the potential benefits of neoadjuvant chemotherapy such as shrinkage of the tumor and therefore potentially breast conserving surgery vs mastectomy as your surgical option after chemotherapy. There is no way to predict whether a response to the study treatment will improve your quality of life or prolong survival. The results of this study may or may not help future breast cancer patients.

Less Likely < 20%
Cardiomyopathy: heart muscle becomes abnormally enlarged or thickened, decreased left ventricle ejection fraction (LVEF), fluid in the sac around the heart (pericardial effusion), inflammation/swelling of the sac around the heart (pericarditis), fast heartbeat with regular rhythm (sinus tachycardia), and fast heartbeat usually in an area above the heart's chambers (supraventricular tachycardia). We will monitor your heart function by echocardiogram every three months as standard of care. Diarrhea Fever associated with low white blood cell count Abdominal pain Mouth sores Nausea Vomiting Body aches Decreased red blood cells and increased liver proteins, these levels will be monitored during the study Headaches or numbness in the hands and feet can occur Lung inflammation (pneumonitis)
Runny, stuff nose, sneezing or cough Acne Skin rash Hives Very Unlikely < 1%  
  
  
Anaphylaxis (allergic reaction which is an abnormal reaction of the body to substances called allergens). Can cause life threatening low blood pressure, shortness of breath and death.  
Rare risk of pulmonary edema (fluid buildup in the lungs) Lung scarring (pulmonary fibrosis) This drug should not be given to anyone who has a known allergy or sensitivity to benzyl alcohol Carboplatin:

Peripheral Neuropathy: Tingling, numbness or pain in fingers or toes that may progress Electrolyte imbalances (Low Potassium or sodium for example)
Vomiting Abdominal pain Nausea (without vomiting)
Bone marrow depression or cytopenias of red blood cells or white blood cells or platelets thereby potentially increasing your risks of anemia, infection or bleeding Increased serum alkaline phosphatase, increased serum AST, these are levels of liver function Hypersensitivity to the medication Weakness Acute Kidney Injury

Severe allergic reaction which is an abnormal reaction of the body to substances called allergens. Can cause life threatening low blood pressure, shortness of breath, and death.  
Loss of appetite Stroke Cardiac Failure Dehydration Redness of the skin Febrile neutropenia (fever in the setting of low white blood cell counts)
High or low blood pressure Injection site reaction (pain, redness, swelling) Fatigue
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Study ID \#: IRB-17-02073 **Form Version Date: 8.23.2019**
Skin rash

More Likely >10%
Cardiomyopathy (heart muscle becomes abnormally enlarged or thickened, decreased left ventricle ejection fraction (LVEF) which is the output of blood from the heart.  
Cardiotoxicity Chest tightness Fatigue Headache Palmar-plantar erythrodysesthesia: rash that can start as redness of palms of hands and plantar aspects of feet and progress to pain and skin peeling of these areas Skin rash Kaposi sarcoma (a rare type of cancer)
Hair Loss Facial swelling Nausea Constipation Diarrhea Loss of appetite Thrombocytopenia (low platelets)
Neutropenia (low white blood cell count)
Leukopenia (low white blood cell count)
Anemia (low red blood cell count)
Weakness Back pain Pharyngitis (throat pain or irritation) Dyspnea (shortness of breath)
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Cardiac arrest Chest pain Tachycardia- accelerated heart rate Dizziness Drowsiness Acne vulgaris Weight loss Dehydration Elevated blood sugar Difficulty swallowing  
Study ID \#: IRB-17-02073 **Form Version Date: 8.23.2019**
Inflammation or irritation of the esophagus Oral candidiasis (thrush or fungal infection of the mouth) Hematuria (blood in the urine)
Hemorrhagic cystitis (bladder irritation resulting in blood in the urine)
Hypersensitivity reaction Nose bleeds Very unlikely < 1%
Anxiety Muscle aches Electrolyte imbalances Skin rash Flatulence (gas)

More likely > 10%
Alopecia (hair loss which may be reversible; onset: 3-6 weeks after start of treatment)
Loss of periods Sterility (loss of fertility) Cytopenias: low red blood cell counts, low white blood cell counts that may increase risk for infection or bleeding Less Likely: 1% to 10%
Abdominal pain Anorexia (an eating disorder characterized by an abnormally low body weight)
Diarrhea Mucositis (painful inflammation of the mucous membranes lining the digestive tract)
Nausea/vomiting Mouth sores Hemorrhagic cystitis Very unlikely < 1%
Acute respiratory distress syndrome: accumulation of fluid in the lungs which can be severe High blood pressure Pneumonia Secondary malignancy Kidney infections Sepsis or systemic infections

Study ID \#: IRB-17-02073 **Form Version Date: 8.23.2019** More Likely >10%
Flushing Swelling in the lower limbs Low blood pressure Hair loss Rash Nausea/vomiting Diarrhea Mouth sores or inflammation Neutropenia (low white blood cells)
Anemia (low red blood cells)
Thrombocytopenia (low platelets)
Alkaline phosphatase increased/AST increased (measures of liver function) Peripheral neuropathy (tingling or numbness in fingers and toes)
Muscle or joint aches or pains Weakness Allergic reaction Infection Less Likely 1% to 10%
Abnormal heart rhythms Nail changes or weakening or breaking Febrile neutropenia (fevers associated with a low white blood cell count)
Bilirubin increased (a measure of liver function)
Very Unlikely <1%
Abnormal heart rhythms Skin infections Severe allergic reaction Skin Rash Blood clots Pancreatitis Docetaxel More Likely >10%
Flushing Lower limb swelling Low blood pressure Hair loss Rash Nausea/vomiting
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Study ID \#: IRB-17-02073 **Form Version Date: 8.23.2019**
Diarrhea Mouth sores or inflammation Neutropenia (low white blood cells)
Anemia (low red blood cells)
Thrombocytopenia (low platelets) Alkaline phosphatase increased, AST increased (measures of liver function, require surveillance)
1% to 10%: Less Likely Abnormal heart rates Nail changes Febrile neutropenia (fevers associated with low white blood cells)
Bilirubin increased (a measure of liver function)
Pegfilgastrim More Likely > 10%
Muscle and skeletal pain Limb pain Less Likely 1-10%
Acute respiratory distress syndrome (ARDS)
Severe allergic reaction Swelling of the body Chest pain Fever Injection site reactions Rash Other Risks Risk of loss of private information; this risk always exists, but there are procedures in place to minimize the risk.

The risks of a blood draw include pain, bruising, and the slight possibility of infection at the place where the needle goes in. Some people feel dizzy or may faint during or after a blood draw.

If you are or become pregnant, this research may hurt your baby or your pregnancy in ways that are unknown. The unknown risks might be minor or might be major (death). You should not become  
  
  
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Clinical trial: NCT03329378
Section: Procedures
Subsections: Description Of What'S Involved:|Study Treatment:

Research activities will take place at Mount Sinai Hospital, Mount Sinai Beth Israel and Mount Sinai West. Screening: After signing this consent form, you will enter the screening phase of the study during which you will have various tests and procedures to determine if you are eligible to participate in this study.  
Your medical history, height, weight, and vital signs ( heart rate, blood pressure, breathing rate and temperature) will be taken. You will have a physical exam and screening echocardiogram (ultrasound of the heart) to assess the function of your heart Depending on the extent of lymph node involvement or abnormal lab values, imaging may be required to rule out metastatic breast cancer (cancer that has spread from the primary site
[place where it started] to other places in the body) so you may also have a CT of your chest, abdomen and pelvis and bone scan or a PET/CT scan to assess the extent of disease. Your breast biopsy will confirm your cancer is Her2+ to be eligible for the study. All of this is considered standard of care.  
Approximately 3 teaspoons of blood will be taken for blood analysis. The blood will be used for a complete blood count, chemistry profile (routine lab tests looking at electrolytes and chemicals in your blood), and liver function tests. If you are a woman of child bearing age, a urine pregnancy test will be performed to ensure you are not pregnant. If you are pregnant you will be excluded from the study. All of this is standard of care.  
For Research Purposes only the following tests will be done:
1. Performing an extra measurement on your baseline echocardiogram called longitudinal strain which is a number we will follow during the study to assess cardiac (heart) toxicity. This is done after the processing of the echocardiogram and is non-invasive. This extra measurement will not be billed to you or to your insurance.  
  
2. Checking a baseline blood test as a marker of heart function, called troponin I (approximately a teaspoon of blood). This test will not be billed to you or to your insurance.  
Once it is determined that you are eligible for the study, you will enter the treatment phase.

The study treatment you get will be chosen by chance, like flipping a coin (randomization). Neither you nor the study doctor will choose what study treatment you get. You will have an equal chance of being given each study treatment.  
Arm A is for the chemotherapy treatment plan AC THP where A stands for doxorubicin and C stands for cyclophosphamide. This treatment is given once every 2 weeks for 4 cycles (a cycle for this regimen is 14 days). Pegfilgastrim will be administered on the second day of each cycle to boost the white blood cells to prevent infection from the chemotherapy during the AC portion. Thereafter you will receive 4 cycles (a cycle is 21 days for this portion of the treatment) of T (taxol) once weekly along with Trastuzumab and Pertuzumab (2 antibodies that target the Her2Neu receptor), given on the first day of the first week of every cycle for a total of 4 treatments. The duration of chemotherapy is approximately 20 weeks. Please see the table below.  
| Arm A AC THP    | Cycle  5  21  days   | Cycle  6 21  days   | Cycle  7 21  days   | Cycle  8 21  days   | Surg ery   |     |     |
|------------------|----------------------|---------------------|---------------------|---------------------|------------|-----|-----|
| Cycle 1          | Cycle 2              | Cycle 3             | Cycle 4             |                     |            |     |     |
| 14 days          | 14 days              | 14 days             | 14 days             |                     |            |     |     |
| Visit Day        | Days 1, 8,  15       |                     |                     |                     |            |     |     |
| Doxorubicin      | X                    | X                   | X                   | X                   |            |     |     |
| Cyclophosphamide | X                    | X                   | X                   | X                   |            |     |     |
| Pegfilgastrim    | X                    | X                   | X                   | X                   |            |     |     |
| Paclitaxel       | X                    | X                   | X                   | X                   |            |     |     |
| Trastuzumab      | Day 1                | Day 1               | Day 1               | Day 1               |            |     |     |
| only             | only                 | only                | only                |                     |            |     |     |
| Pertuzumab       | Day 1                | Day 1               | Day 1               | Day 1               |            |     |     |
| only             | only                 | only                | only                |                     |            |     |     |
| Days 1, 8,  15   | Days  1, 8,  15      | Days 1, 8,  15      |                     |                     |            |     |     |
| Day              | Day                  | Day                 | Day                 | Day                 | Day        | Day | Day |
| 1                | 2                    | 1                   | 2                   | 1                   | 2          | 1   | 2   |  
AC takes approximately 3 hours to administer by infusion (a method of putting drugs into the bloodstream through a needle or catheter) THP takes approx. 3-4 hours to administer by infusion. Pegfilgastrim is an injection given subcutaneously (a needle applied just under the skin).  
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Clinical trial: NCT03329378
Section: Purpose of Research
Subsections: Purpose Of This Research Study:

The purpose of this study is to determine if one chemotherapy regimen administered before surgery works better than another regimen to treat early stage Her2+ breast cancer and to determine how harmful each regimen is to the function of the heart. Her2 positive breast cancer is a type of breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). This protein promotes the growth of cancer cells. One option for the treatment of Her2 positive breast cancer is the use of chemotherapy to shrink the breast tumor before surgery. This is called neoadjuvant chemotherapy We will be measuring how much tumor may or may not be present at the time of surgery after 1 or 2 different regimens of chemotherapy has been given to shrink the tumor. When there is no cancer left at the time of surgery this is called a pathologic complete response (pCR). We are measuring the rates of pathologic complete response for each chemotherapy regimen. The two chemotherapy regimens to which patients may be randomized (like the flip of a coin) are:
**Dose Dense AC  THP** which contains doxorubicin (A), cyclophosphamide (C) every 2 weeks for 4 cycles followed by paclitaxel (T), trastuzumab (H) and pertuzumab (P) for a total of 12 weeks and
**TCHP** which contains Docetaxel (T), Carboplatin (C), Trastuzumab (H), Pertuzumab (P) every 3 weeks for 6 cycles for total of 18 weeks.  
Doxorubicin, cyclophosphamide, paclitaxel, docetaxel and carboplatin are standard chemotherapeutics. Trastuzumab and Pertuzumab are monoclonal antibodies which are specific proteins or antibodies directed against the Her2 protein or receptor on breast cancer cells. Trastuzumab and Pertuzumab are FDA approved in the treatment of Her2 positive breast cancer. Pertuzumab is a newer agent and is believed to contribute to higher rates of pCR. You may qualify to take part in this research study because you have early stage breast cancer or inflammatory breast cancer that is Her2+ and have baseline normal heart function. After completion of the neoadjuvant chemotherapy, Anti-Her2 therapy will be continued on a specified schedule as per standard of care for a total of a year for BOTH regimens. After completion of the neoadjuvant chemotherapy you will be evaluated for surgical treatment by your breast surgeon. You will be offered surgery and radiation as determined by your breast surgeon and radiation oncologist.  
  
After completion of surgical and/or radiation therapy, patients with estrogen receptor (ER)–positive and/or progesterone receptor (PR)–positive tumors will be offered an antiestrogen pill for further treatment of their breast cancer which is standard treatment.
Clinical trial: NCT03329378
Section: Withdrawal from Study
Subsections: In Case Of Injury During This Research Study:|Ending Participation In The Research Study:|Can You Change Your Mind?

If you are injured or made sick from taking part in this research study, medical care will be provided. Generally, this care will be billed to you or your insurance in the ordinary manner and you will be responsible for all treatment costs not covered by your insurance, including deductibles, co-payments and coinsurance. This does not prevent you from seeking payment for injury related to malpractice or negligence. Contact the investigator for more information. You are not waiving any legal right to seek additional compensation through the courts by signing this form.

You may stop taking part in this research study at any time without any penalty. This will not affect your ability to receive medical care at any of the Mount Sinai Health System hospitals or to receive any benefits to which you are otherwise entitled. If you decide to stop being in the research study please contact the Principal Investigator or the research staff. If you decide to stop being in the research study, the following may occur: If you were getting benefit from the study drug(s) you may experience progression off the drug and need to discuss alternative therapies with your provider. If you stop being in the research study, already collected information may not be removed from the research study database and will continue to be used to complete the research analysis. You may be asked whether the investigator can collect information from your routine medical care. If you agree, this data will be handled the same as research data. You may also withdraw your permission for the use and disclosure of any of your protected information for research, but you must do so in writing to the Principal Investigator at the address on the first page. Even if you withdraw your permission, the Principal Investigator for the research study may still use the information that was already collected if that information is necessary to complete the
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research study. Your health information may still be used or shared after you withdraw your authorization if you have an adverse event (a bad effect) from participating in the research study. Withdrawal without your consent: The study doctor, the sponsor or the institution may stop your involvement in this research study at any time without your consent. This may be because the research study is being stopped, the instructions of the study team have not been followed, the investigator believes it is in your best interest, or for any other reason. If specimens or data have been stored as part of the research study, they too can be destroyed without your consent. More possible reasons for removal from the study include: subjects will be removed from the research study if they become pregnant, potentially if they have tumor progression, or experience certain adverse events such as cardiac events.

You may withdraw your permission for the use and disclosure of any of your protected information for research, but you must do so in writing to the Principal Investigator at the address on the first page. Even if you withdraw your permission, the Principal Investigator for the research study may still use your protected information that was already collected if that information is necessary to complete the study. Your health information may still be used or shared after you withdraw your authorization if you should have an adverse event (a bad effect) from being in the study. If you withdraw your permission to use your protected health information for research that means you will also be withdrawn from the research study, but standard medical care and any other benefits to which you are entitled will not be affected. You can also tell us you want to withdraw from the research study at any time without canceling the Authorization to use your data. If you have not already received it, you will also be given The Hospital's Notice of Privacy Practices that contains more information about how The Hospital uses and discloses your protected health information. It is important for you to understand that once information is disclosed to others outside Mount Sinai, the information may be re-disclosed and will no longer be covered by the federal privacy protection regulations. However, even if your information will no longer be protected by federal regulations, where possible, Mount Sinai has entered into agreements with those who will receive your information to continue to protect your confidentiality. If as part of this research project your medical records are being reviewed, or a medical history is being taken, it is possible that HIV-related information may be revealed to the researchers. If that is the case, the following information concerns you. If this research does not involve any review of medical records or questions about your medical history or conditions, then the following section may be ignored.