Clinical trial: NCT03501979
Section: Alternatives
Subsections: Alternatives

There are other options to treat metastatic HER2 positive breast cancer with leptomeningeal disease that may include radiation, chemotherapy injected through the spinal canal, or chemotherapy given intravenously. Your doctor will discuss these other options with you. Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020
Clinical trial: NCT03501979
Section: Confidentiality
Subsections: Confidentiality

Information obtained about you for this study will be kept confidential to the extent allowed by law. However, research information that identifies you may be shared with the UAB Institutional Review Board (IRB) and others who are responsible for ensuring compliance with laws and regulations related to research, including people on behalf of MD Anderson Cancer Center, Seattle Genetics, Inc., and Johns Hopkins University on behalf of the TBCRC; the Office for Human Research Protections (OHRP) and FDA. The information from the research may be published for scientific purposes; however, your identity will not be given out. This consent document will be placed in your file at UAB and the document will become part of your medical record chart. 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 System affiliated entities so that the costs for clinical services can be appropriately paid for by either the study account or by the patient/patient's insurance. Your medical record may indicate that you are on a clinical trial and will provide the name and contact information for the principal investigator. Monitors, auditors, the Institutional Review Board for Human Use, and regulatory authorities will be granted direct access to your original medical records for verification of trial procedures and/or data without violating confidentiality. 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. A federal law, called the Genetic Information Nondiscrimination Act (GINA), generally makes it illegal for health insurance companies, group health plans, and most employers to discriminate against you based on your genetic information. This law generally will protect you in the following ways:  
- Health insurance companies and group health plans may not request your genetic information that we get from this research.  
- Health insurance companies and group health plans may not use your genetic information when making decisions regarding your eligibility or premiums.  
- Employers with 15 or more employees may not use your genetic information that we get from this research when making a decision to hire, promote, or fire you or when setting the terms of your employment.
Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020 Be aware that this new federal law does not protect you against genetic discrimination by companies that sell life insurance, disability insurance, or long-term care insurance, nor does it protect you against genetic discrimination by all employers.
Clinical trial: NCT03501979
Section: Duration of Study Involvement
Subsections: At Screening/Baseline - Within 28 Days Before Enrollment/Starting Treatment|Each Cycle Visit, Day 1|Every 2 Cycles (42 Days)|How Long Will I **Be In This Study?**

After you sign this informed consent form, tests or procedures will be done to find out if you can be in the study. These include the following:
- Review of your current symptoms, medications, active medical problems, and your medical history
- Physical examination (performed by medical oncologist) - Neurologic physical exam (performed by a neurologist/neuro-oncologist) - Vital signs (blood pressure, heart rate, temperature, and breathing rate) - ECHO (echocardiogram) or MUGA (multiple gated acquisition) scan to measure how much blood your heart pumps out with each heartbeat
- Performance status (measurement of how well you can carry out daily activities) - Blood draws for routine laboratory tests and cancer biomarker studies (approximately 4 tablespoons). A biomarker is a molecule or cell in your body that can be found in your blood, body fluid or tissue and a biomarker can be used to measure your health.  
- Cerebral spinal fluid (CSF)standard evaluation - the study doctor will obtain a CSF sample to assess cell count, evidence of tumor in fluid, and cancer research biomarkers.  
- Blood draw to test for Hepatitis B and Hepatitis C (approximately 2 teaspoons). If this test is positive you may be asked to have another test to confirm the first result
- Tumor assessment by CT scan or MRI that takes cross-sectional pictures (slices) of your body
- MRI of your brain and spine
- Pregnancy Test (blood or urine) - only for participants of childbearing potential.

- History and physical exam (performed by medical oncologist)
- Neurologic physical exam (performed by a medical oncologist and/or neurologist/neurooncologist)
- Performance status
- Vital signs (blood pressure, heart rate, temperature, and breathing rate)
- Blood tests - CBC with differential, ALT, AST, alkaline phosphatase, total bilirubin, BUN/creatinine.  
- Treatment will be given - CSF samples
- Routine blood samples
- Symptom Burden and Quality of Life (QOL) Questionnaires Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020

- MRI brain and spine Every 4 cycles (84 days)
- CT chest/abdomen/pelvis (CAP) and bone scan or PET/CT  
End of Study
- History and physical exam (performed by medical oncologist)
- Performance status
- Vital signs (blood pressure, heart rate, temperature, and breathing rate) - Neurologic physical exam (performed by a neuro-oncologist or neurologist) - CSF standard evaluation - MRI brain and spine
- Symptom Burden and Quality of Life (QOL) Questionnaires

The study is expected to last for 3 years. Clinical trial participants will receive treatment until disease progression or unacceptable toxicity or death. Clinical trial participants will be followed every 6 weeks via telephone call and/or chart review for 6 months after leaving the study, or until death, whichever occurs first. Participants who discontinue the study for unacceptable side effects will be followed in the same method. In the event that a participant does not continue her post-study care at the clinic, every attempt will be made to collect this post study follow up information either by direct contact or through communication with your outside physician(s). Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020
Clinical trial: NCT03501979
Section: Participant's Rights
Subsections: What Are My Rights If I **Take Part In This Study?**|What Are My Legal **Rights?** You Are Not Waiving Any Of Your Legal Rights By Signing This Informed Consent Document. Biospecimens **For Research**

If you take part in this study, you may leave the study at any time. No matter what decision you make, there will be no penalty to you and you will not lose any of your regular benefits. Leaving the study will not affect your medical care. You can still get your medical care from your medical team. Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020 By signing this form, you do not waive any of your legal rights to seek payment in the case of injuries resulting from this study. The treating institution will receive direct and indirect payment from Seattle Genetics, Inc. and Johns Hopkins University on behalf of the TBCRC (the study supporters) for their time spent doing research and general administrative services for this study. Seattle Genetics, Inc., and other company(ies) involved in the research studies done on blood and tissue samples may benefit financially from this research. You will receive no financial benefit from this research. If you decide to sign this consent form, you are giving your bodily fluids and tissue samples collected during the study and any new drugs that may be developed from your fluids or samples.

Your bio-specimens (tissue and blood samples) are being used for this research study. As part of the study, we may perform the following research studies on them. In addition, we will ask your permission in the next section for the use of any leftover bio-specimens (that is, samples remaining or "leftover" after the research for this study is completed) to be used for future research and the option to contact you in the future. We may use genetic analysis in some of the research we do on your samples. Researchers can learn a lot by studying genes. Genes are pieces of DNA that give instructions for building the proteins that make our bodies work. DNA stores these instructions in the form of a code. This is the code that you inherit from your parents and that you pass on to your children. One of the methods we might use to study your samples is called whole genome sequencing. This allows us to look at some or all of your genetic code. Researchers may also use other methods as they are developed. Studying genes along with your health information will help us to better understand Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020 what causes certain diseases. It may also help us to understand how different patients respond to treatment. This knowledge could help us to develop treatments for everyone. What we learn about you from your samples will not be put in your health record and will not be shared with you or your doctor. No one else (like a relative, boss, or insurance company) will be given your test results. Your samples will only be used for research and will not be sold. Health insurance companies and group health plans may not request your genetic information that comes from this research. We will remove your name and any other information that could directly identify you from your samples and information. We will replace this information with codes. We will keep a master list that links those codes to your materials. Only certain study staff can access this master list. We will keep the samples in locked freezers in locked buildings. We will keep health information and research data on secure computers. These computers have many levels of protection. The Genetic Information Nondiscrimination Act (GINA) may help protect you from health insurance or health-related employment discrimination based on genetic information. The law provides that health insurance companies and group health plans:
- May not ask for genetic information from this research and - May not use genetic information when making decision about eligibility or premiums The law will not stop health insurance companies from using genetic information to decide whether to pay claims. The law does not apply to other types of insurance (such as life, disability or long-term care). Despite the GINA protections and the best efforts of the research team to protect your information, you may still be at risk if information about you were to become known to people outside of this study.
Clinical trial: NCT03501979
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Are The Risks Of Participating In The Study?|Risks Associated With **Tucatinib**|Liver Function Problems|Diarrhea|Other Important Side Effects Interactions **With Other Medications**|Fertility, Pregnancy, And Breastfeeding Risks|Kidney Function Problems|Risks Associated With **Capecitabine**|Risks Associated With **Trastuzumab**|Is It Safe?|Can It Be Removed?|Risk Of Drawing Csf From Ommaya Reservoir|Radiation Risks Associated With Scans And X-Rays:|Risks Associated With Ct Scans:|Risks Associated With Mri **Scans:**|Risks Associated With Mri **Scans With Gadolinium As A Contrast Agent:**|Reproductive Risks:|Birth Control Requirements|Drug Interactions:|Non-Physical Risks:|Risks Associated With Genomic Testing|What Happens If I Am Injured Because I **Took Part In This Study?**|What Are The Risks?

Your condition may not improve and could even worsen if you take part in this study. You may have side effects as a result of your participation in this study. A side effect is an unwanted or unintended problem that may be caused by taking a drug. If you take tucatinib, capecitabine and trastuzumab certain side effects and discomforts may happen after you take tucatinib, capecitabine and trastuzumab. Tucatinib, capecitabine and trastuzumab may affect several organs (or parts) of your body including, but not limited to, effects on your cancer cells. Side effects that you may have during this study may be minor, life-threatening, or even cause your death sooner than would have been expected from your cancer. You may also have other side effects that doctors don't know about yet. Your study doctor and other medical staff will be performing the procedures to reduce any side effects that may occur; however, you may have unforeseen side effects. You will be monitored closely (with blood tests, physical exams, and heart scans) for any side effects and the study therapy will be stopped if serious side effects happen. You will be asked to report any side effects or changes in your health to your doctor, no matter how minor the changes may seem to you. Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020 Taking other drugs (including alcohol, over-the-counter medications, prescriptions, illegal drugs, herbal preparations, or nutritional supplements) may cause additional side effects or even lifethreatening reactions when combined with the drugs or experimental agents used in this study. It is very important that you discuss ALL medications that you are taking with your study doctor.

The most common side effects reported in patients with cancer treated with tucatinib include:
- Feeling sick to your stomach (nausea) - Watery poop (diarrhea) - Feeling tired (fatigue) - Throwing up (vomiting) - Rash - Difficulty pooping (constipation)
- Cough
- Pain in your arms or legs (pain in the extremity) - Back pain - Headache - Infection that could cause frequent and painful urination (urinary tract infection) - Muscle pain (myalgia) - Muscle and bone pain in your chest (musculoskeletal chest pain) - Belly pain (abdominal pain) - High levels of liver enzymes (increased liver function tests). This may mean you have a problem with your liver.  
- Not wanting to eat (anorexia) - Feeling dizzy (dizziness) - Feeling out of breath (dyspnea) - Patchy redness on your skin (erythema) - Low levels of magnesium in your blood (hypomagnesemia). You may feel weak, have an abnormal heartbeat, muscle cramps, or seizures.  
- Heavy sweating while sleeping (night sweats) - Infection in the nose, sinuses or throat (upper respiratory tract infection). You may have fever, pain, or a hard time breathing.

Some patients who took tucatinib had problems with their liver. Your doctor will run tests to check that your liver is working properly during your treatment with tucatinib. Your doctor may change your tucatinib dose based on the test results.

Tucatinib can cause severe watery poop (diarrhea). If you have watery poop, tell your doctor right away. Your doctor may change your tucatinib dose if you have watery poop. Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020

Tucatinib may change how your body reacts to some other drugs, which could stay in your body longer than usual. While you are taking part in this study, you might need to stop some medications or replace them with other medications. If you can't stop taking these medications, your doctor might need to change how much you take. Your doctor might also need to watch your health more closely while you are taking part in this study.

Tucatinib could hurt or kill a baby developing in the womb. You should not try to get pregnant or get your partner pregnant while you are in this clinical trial or for 30 days after your last dose of tucatinib. If you are pregnant or breastfeeding, you can't be in this study. We will remove anyone who becomes pregnant while on study from the study treatment immediately. Tucatinib could hurt a breastfeeding baby. You must not breastfeed during the study or for 30 days after you stop treatment with tucatinib.  
Tell your study doctor **right away** if
- you or your partner become pregnant while you are in this study - you think that you are pregnant while taking part in this study - you or your partner become pregnant within 30 days after being treated with Tucatinib.
Page 9

Some patients who got tucatinib had higher creatinine levels. This could mean that there are problems with your kidneys. If this happens, it's usually within the first treatment cycle. Patients who have had increased levels of creatinine had these levels stay increased while they were getting treated. The levels went back down after treatment stopped. Seattle Genetics would like to follow any pregnancy that happens during this study during the pregnancy and for some time after the birth of any child. If you give permission, we will follow your baby for up to 8 weeks after birth, or longer if there are problems. If your partner becomes pregnant, we will ask for their consent to follow their pregnancy and the health of the baby.

The most common side effects associated with capecitabine include:
- Nausea - Diarrhea
- Abdominal pain
- Tiredness Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020  
- Acid reflux
- Eye tearing
- Fatigue (tiredness)
- Changes in taste
- Mouth sores
- Hair thinning - Hand-foot syndrome (rash or skin changes on the hands and feet) - Peripheral neuropathy (numbness and tingling in fingers and toes) - Low blood counts
- Hyperbilirubinemia (abnormal liver function)
Management of capecitabine side effects may include temporary interruption, dose reduction, or treatment discontinuation with capecitabine.

Trastuzumab has different side effects that your study doctor will discuss with you. The most common side effects are:  
- Allergic reaction to infusion
- Nausea/vomiting
- Tiredness
- Fever/chills - Swelling of the legs and arms
- Anemia (low red cell count)
- Neutropenia (low white blood count)
- Congestive heart failure (damage to heart)
Note: Management of left ventricular dysfunction (heart failure), or infusion reactions may include temporary interruption or stopping treatment of trastuzumab permanently.

Ommaya reservoirs are generally safe. However, the procedure to place them carries the same risks as any other surgery involving your brain, including:
- Infection - Bleeding into your brain - Partial loss of brain function To prevent infection, your doctor might prescribe you antibiotics following the procedure. Talk to your doctor about any concerns you have about complications. They can go over their approach with you and let you know about any additional steps they'll take to lower your risk of having complications.

Ommaya reservoirs usually aren't removed unless they cause problems, such as an infection. Though at some point in the future you may no longer need your Ommaya reservoir, the process to remove it carries the same risks as the process to implant it. Generally, removing it isn't worth the risk. If you have an Ommaya reservoir and are considering having it removed, make sure you go over the potential risks with your doctor.

- Pain - Bleeding
- Infection
- Headache
- Nausea/Vomiting
- Others as explained to me by my doctor
o **Note:** This procedure is required for the first stage or the first 15 patients to enroll on the study so that your CSF can be collected for standard evaluation and to study drug levels in the fluid. If you are enrolling in the study on the 2nd stage, it is strongly recommended that you have an ommaya reservoir placed to help with collection of your CSF during the study for standard evaluations, which help determine if you are responding to the treatment. Alternatively, this can be done via lumbar puncture. Your study doctor will clearly discuss the stage of the study in which you will be enrolled. Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020

While you are in this research study, CT scans, PET/CT scans, bone scans, x-rays, and/or other radioactive agents may be used to evaluate your disease status. The frequency of these exams is similar to that which you would receive as standard care. There is thought to be a small but increased risk of cancers associated with radiation in the long term over many years.

In this study, you will be exposed to some radiation from the CT scan[s]. The total radiation from each [combined chest, abdominal and pelvic] CT scan is approximately equal to [five years] of exposure to natural background radiation. Background radiation is radiation normally received from sources such as cosmic rays and natural radioactivity in building materials and the ground. There is a small risk that the radiation may cause cancer or other radiation effects in several years. To prepare you for your CT scan, a liquid called a "contrast dye" may be injected into your veins to improve the quality of the image. There is a small possibility that you could have a severe allergic reaction to this dye that could cause injury or death. If you have any kidney problems, the dye may cause other medical problems.  
- If you have any kidney problems or have ever had an allergic reaction to contrast dye, you must let the study physician know as soon as possible.

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. A magnetic resonance imaging (MRI) exam is a test that uses magnetic fields and radio waves to generate images of the inside of your body. You will be placed inside a scanner and asked to lie still for approximately 30 minutes. This is a noisy exam; you will be given earplugs to protect your hearing. During the scan, a liquid will be injected into your vein to Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020 improve the quality of the scan. MRI has negligible risks for most people; however, if you have any metal objects in your body MRI may not be safe for you and you will not be allowed to take part in this study.

A few side effects of gadolinium injection such as mild headache, nausea, and local pain may occur. Rarely (less than 1% of the time), low blood pressure and lightheadedness occurs. This can be treated immediately with intravenous fluids. Very rarely (less than on in one thousand), patients are allergic to gadolinium. These effects are most commonly hives and itchy eyes, but more severe reactions have been seen which result in shortness of breath. Patients with severe kidney disease sometimes have a bad reaction to gadolinium contrast. The condition is called nephrogenic sclerosing fibrosis (NSF). It can cause skin to tighten or scar and can damage internal organs. Sometimes it can be life threatening. There are no reports of NSF in patients with normal kidney function. Before you have a MRI scan requiring an injection of gadolinium contrast, you will have a blood test in order to check the function of your kidneys. Based on your medical history and the results of the test, a doctor will decide whether it is safe for you to undergo the MRI scans.

We do not know if the study drug will affect mother's milk or an unborn fetus. Therefore, breastfeeding and pregnant women are not allowed to take part in the study. If you are pregnant or become pregnant, there may be risks to the embryo or fetus. Administration of the drug resulted in harm to the fetus of pregnant animals and could cause harm or death to a baby developing in the womb. Women who can become pregnant must take a pregnancy test before the start of the study. While participating in this research study, you should not become pregnant or father a child, and should not nurse a baby as the treatment may indirectly affect an unborn child. If you are sexually active and are at risk of causing a pregnancy, you and your female partner(s) must use a method to avoid pregnancy that works well or you must not have sex. You must agree to use an adequate method of birth control during the study (such as surgical sterilization, IUDs or abstinence). Barrier methods such as diaphragms or condoms may also be used if a spermicide is used with them. Women cannot use birth control pills due to effects that they cause on breast cancer. If you think you may be pregnant (have a missed or late menstrual period) at any time during this study, you must let the study doctor know immediately. Women who become pregnant will be removed from the study. Let your doctor know immediately if you become pregnant or find out that you are going to be the father of a child. Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020

If you can get pregnant, you must use a safe birth control method while you are taking part in this study. Safe birth control methods fail less than 1% of the time. This means that if 100 people used this birth control for a whole year, at most 1 person would get pregnant. You must use safe birth control methods while you take part in the study and keep using them for 30 days after stopping all study treatment. If you don't use safe birth control methods while you take part in the study, we might decide that you can't take part in the study anymore. The safe birth control methods that you can use are:
- hormonal methods that have both estrogen and progestogen. These can be taken by mouth
(birth control pills), inserted into the vagina, or absorbed through the skin (patches). hormonal methods that have only progestogen. These can be taken by mouth (birth control pills), injected, or implanted in your body.  
- intrauterine device (IUD)
- intrauterine hormone-releasing system
- tubal ligation for females ("tubes tied") - vasectomy for males Talk with your doctor about your birth control options. You may also choose to not be sexually active (complete abstinence) while you take part in the study. If you are able to get someone pregnant, and your partner is able to get pregnant, you must use a barrier method such as a male or female condom when you are taking part in the study. You must keep using a barrier method for 30 days after finishing treatment with tucatinib. If you think you may be pregnant (have a missed or late menstrual period) at any time during this study, you must let the study doctor know immediately. Women who become pregnant will be removed from the study. Let your doctor know immediately if you become pregnant or find out that you are going to be the father of a child.

The other medications you take may affect the study drug(s) in ways that we do not know. For your safety, you must tell the study doctor or nurse about all the prescription drugs, herbal products, overthe-counter (OTC) drugs, vitamins, and natural remedies that you are taking before you start the study and before taking any of these products while you are on the study. Please be sure to tell us also about any changes you make with your medications during your participation. Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020

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. During the research study, you will be provided with any new information that may affect your health or willingness to participate. You may be asked to sign a new consent form that shows that you have been informed of new information relating to this research study.

Despite the GINA protections and the best efforts of the research team, there may still be a risk if information about you were to become known to people outside of this study. Genetic information is unique to you, even without your name or other identifiers. For this reason, genetic information like DNA may be used to identify you and possibly your family members. We have procedures (such as, labeling your biospecimens with a password protected code known only to select research staff) to prevent people working with your DNA from discovering if it belongs to you. However, there is the risk this can happen as new ways of tracing genetic information are being developed that may make re-identification of genetic information possible.

Side effects or harm are possible in any research study, and you might be injured or develop medical complications because you take part in this study. Medical complications could occur through no fault of yours or the study doctors involved. Known side effects have been described in this consent form, and there may also be unexpected side effects. It is important that you tell your study doctor if you feel that you have been injured because of taking part in this study. In the event you have an injury, the treating hospital will offer you the care needed to treat injuries directly resulting from taking part in this research. These treatments will be billed to your insurance company. You will be responsible for deductibles and co-payments. There are no plans to pay you or give you other compensation for the injury. Your health insurance company may or may not pay for treatment of injuries as a result of your taking part in this study. You should consult with your insurance company if you have questions. Additional reimbursement or compensation for study-related injuries (such as payments for costs like lost wages, or for pain and suffering, or for expenses other than medical care) are not provided. You do not give up any of your legal rights to seek payment for study-related injuries by signing this form or by agreeing to participate in this study.

One risk of giving samples for this research may be the accidental release of your name that could link you to the stored samples and/or the release of results of the tests run on your samples, including genetic testing. There are safeguards in place such as coding your samples and information, secure buildings and equipment, and the Genetic Information Nondiscrimination Act (GINA) as described previously.
Clinical trial: NCT03501979
Section: Procedures
Subsections: How Is This Study Designed?|Screening Tests And Procedures:|Biospecimen Samples|Mandatory Ommaya Reservoir Placment|Preparation:|Recovery

If you complete the consent process, then you may be eligible to participate in this study. Eligible participants will receive tucatinib, capecitabine, and trastuzumab.  
The research team wants to learn:
- What effect tucatinib has (if any) when given with capecitabine and trastuzumab on the growth of tumors in the brain and meninges (tissues that surround the brain and/or spinal cord).
Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020 STUDY DESIGN

As part of the study screening process, this consent form must be signed. The following tests and procedures will be done during screening to determine if you are eligible to participate in the study. It is possible that these tests may show that you can't take part in the study. If this happens, your doctor will discuss these reasons with you.

Biospecimens will be collected in this study. Biospecimens may include any of the following: blood, tissue, saliva, urine, bone marrow, cells, CSF, etc. Most biospecimens contain DNA, which is the genetic code for each person. In this study, the planned biospecimen samples are blood and spinal fluid. As part of this study, we may collect DNA (genetic information) about you and these data will be used for research purposes. If you would like to review the information for this study, ask the study team doctor for the ClinicalTrials.gov study registration number. Also, the results of the trial will be available on the Translational Breast Cancer Research Consortium website.

All patients enrolled on the first stage of the study, MUST undergo MANDATORY placement of an ommaya reservoir if you do not already have one in place. An Ommaya reservoir is a small drum-like device that is placed under the skin of the skull to give chemotherapy and/or medicines. Placement of an Ommaya reservoir is usually recommended as standard of care in patients with newly diagnosed leptomeningeal disease and will be covered by your insurance. Although the reservoir is not being used to deliver chemotherapy to the brain in this study, it will be useful to assess your response to Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020 treatment, as determined by your doctor. If you have one and/or have one placed, it will also be used to collect the study-required CSF samples rather than needing to undergo repeated lumbar punctures. To collect samples from the reservoir, it works similar to a port in that it is tapped or accessed with a needle to remove or collect CSF fluid. This fluid is then sent to the lab to detect any abnormal cells or collected for the research study. The risks of drawing CSF fluid are also as noted above. Your doctor can explain the standard of care ommaya reservoir placement procedure and discuss the risks with you.

Getting an Ommaya reservoir implanted does require some preparation, such as:  
- Not drinking alcohol once the procedure is scheduled - Not taking vitamin E supplements within 10 days of the procedure - Not taking aspirin or medications containing aspirin during the week before the procedure - Telling your doctor about any additional medications or herbal supplements you take - Following your doctor's guidelines about eating and drinking before the procedure

Once the Ommaya reservoir is placed, you'll feel a small bump on your head where the reservoir is. You'll likely need a CT scan or an MRI scan within a day of your surgery to make sure it's correctly placed. If it needs to be adjusted, you may need a second procedure. While you recover, keep the area around the incision dry and clean until your staples or stitches are removed. Be sure to tell your doctor about any signs of infection, such as:  
- Fever - Headaches - Redness or tenderness near the incision site - Oozing near the incision site - Vomiting - Neck stiffness - Fatigue
Once you have healed from the procedure, you can return to all of your normal activities. Ommaya reservoirs don't require any care or maintenance. Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020
Clinical trial: NCT03501979
Section: Purpose of Research
Subsections: What Is A **Clinical Study?**|Why Is This Study Being Done?

A clinical study is a research study that tests the effects of a new medicine or treatment in people. Your study doctor will explain the study to you. The study will only include people who understand the study, meet the study's entry criteria, and choose to be in it. If you choose to volunteer for this study, you will be asked to sign this form. This process is called informed consent. This form explains what the study is about, how it will be done, the possible risks, benefits, and side effects of participating in the study and your responsibilities as a participant. This form will answer some questions about the study, but you should speak with your study doctor if you have additional questions. Please take your time to review the information in this form carefully. You may take home an unsigned copy of this form for review before making a decision. If you have any questions about the study, or if this form has any words that you do not understand, ask your study doctor or the study staff. You may also want to talk to others (for example, your friends, family, or other doctors) about being in this study. Prot Version: 20-Nov-20 Consent Version 11.0: 20 Nov 2020 You do not have to be in this study. You are free to say 'yes' or 'no', or to drop out at any time. No penalty or loss of benefits will occur if you say 'no' or stop participating. Whatever—and wheneveryou make your decision, your regular medical care will not be affected by your decision.

The purpose of this study is to evaluate a new treatment for patients with HER2+ Metastatic Breast Cancer (MBC) with leptomeningeal disease (LMD). Currently, there is no standard of care for the treatment of metastatic HER2-neu positive (HER2+) metastatic breast cancer (MBC) with leptomeningeal disease (LMD). When breast cancer has spread to the meninges (tissues that surround the brain and/or spinal cord), LMD is diagnosed. LMD is a rare and fast growing form of cancer with few treatment options. Therefore, further study in search of new treatments is needed. We want to find out what effects, good and bad, using a combination of tucatinib and trastuzumab with capecitabine has on patients with HER2+ MBC with LMD. We think that this combination therapy will be safe and well-tolerated with few side effects and will control LMD and disease in the body. We also hope that this combination of drugs will improve survival with few side effects in patients diagnosed with metastatic breast cancer with LMD. As part of this study we will also collect samples, such as blood and spinal fluid, to assess the effects of the drug in the body and on the cancer, which may help us to understand why patients do and do not respond to therapy.
Clinical trial: NCT03501979
Section: Voluntary Participation
Subsections: Voluntary Participation And **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 for follow-up care. You may be removed from the study without your consent if the study doctor decides it is not in the best interest of your health, or if you are not following the study rules.