Clinical trial: NCT01554371
Section: Alternatives
Subsections: Are There Benefits To Taking Part In The Study?|What Other Choices Do I Have If I Do Not Take Part In This Study?|Benefits

Taking part in this study may or may not make your health better. While doctors hope eribulin combined with cyclophosphamide will be more useful against cancer compared to the usual treatment, there is no proof of this. We do know that the information from this study will help doctors learn more about eribulin as a treatment for cancer. This information could help future cancer patients.

If you choose not to participate in this research study, other procedures or treatments for your cancer could include:
Surgery to remove tumors Radiation to shrink tumors Other anticancer therapy (either experimental or not experimental), which may include cyclophosphamide or other chemotherapy.  
Getting no treatment Getting comfort care. This type of care could help reduce pain, tiredness, appetite problems and other problems caused by the cancer. It does not treat the cancer directly, but instead tries to improve how you feel. Comfort care tries to keep you as active and comfortable as possible.
Depending on your type of cancer, its location and your general condition, all, some, or none of these alternatives may be appropriate. Another choice available to you is simply to receive supportive care to help manage only the symptoms and pain produced by your cancer. Your study doctor will discuss the other treatments available to you for your cancer. Please talk to your doctor about your choices before deciding if you will take part in this study.

The benefits of research using blood sample include learning more about what causes cancer and other diseases, how to prevent them, and how to treat them.
Clinical trial: NCT01554371
Section: Confidentiality
Subsections: Will My Medical Information Be Kept Private?

We will do our best to make sure that the personal information in your medical record is kept private. However, we cannot guarantee total privacy. Your personal information may be given out if required by law. If information from this study is published or presented at scientific meetings, your name and other personal information will not be used.  
Organizations that may look at and/or copy your medical records for research, quality assurance, and data analysis include:
The sponsor (Eisai, Inc.), it's affiliated Eisai companies, and it's consultants who are helping to conduct this study Government agencies such as the National Cancer Institute (NCI) and the Food and Drug Administration (FDA), involved in keeping research safe for people.  
The University of California
Participation in research may involve a loss of privacy, but information about you will be handled as confidentially as possible. A medical record will be created because of your participation in this study. Your consent form and some of your research test results will be included in this record. Therefore, your other doctors may become aware of your participation. Hospital regulations require that all health care providers treat information in medical records confidentially.
Clinical trial: NCT01554371
Section: Duration of Study Involvement
Subsections: How Many People Will Take Part In This Study?|When You Are Finished Receiving Eribulin And Cyclophosphamide...|How Long Will I Be In The Study?

Up to 18 patients will participate in this study in the first portion of this study (Phase Ib). Approximately 40 patients will participate in the phase II portion. A combined total of 58 subjects will be enrolled at UCSF in both phases of the study.

If you decide to discontinue your participation in the study or if your study doctor decides you should not continue in the study, the following procedures will be carried out within 30 days after you receive your last dose of study drug:  
Physical exam Performance test Laboratory/blood tests Blood sample for research tests Neuropathy assessment
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Review of any medications you are taking Review of any side effects you may be experiencing Neuropathy questionnaire Quality of Live (QOL) questionnaire Radiographic studies which may include a CT scan (to monitor the cancer in your organs), PET/CT scan or bone scan (if your cancer has spread to your bones)
Study location: Study procedures will be done at UCSF, Mt. Zion Campus,
.

You may continue participating in the study as long as the doctor feels you are benefitting from the treatment, or until you no longer wish to participate. Your study doctor or the sponsor may also decide to end your participation at any time without your approval if:
The study is stopped by the Sponsor or the FDA for any reason You fail to follow instructions given by the study doctor There is a change in your medical condition The study doctor believes it is best for you to no longer be in the study For your safety, you will be asked to return to this office for a follow-up visit if you leave the study. Your visit may include tests like physical exams and blood draws. Your visit may also include questions about your medical condition. It is important that you tell the study staff any problems or changes in the way you felt while you were in the study. The researchers will continue to monitor your health for up to 10 years after you complete the final study visit. This will involve reviewing your medical record periodically to see how you are doing.
Clinical trial: NCT01554371
Section: Participant Responsibilities
Subsections: What Are My Responsibilities While I Am In The Study?

It is important that you follow the instructions of the study doctor and study team. It is important that you come to all of your scheduled study visits. It is also important that you follow the schedule when you take the study drug. It is important that during the study, you tell the study doctor and/or the study team all changes in how you feel. You need to tell them even if you do not believe these changes are related to the study. This may include mental or emotional changes. You will be checked during the study for side effects. You will also be checked for other injuries or illnesses that may happen while you are in the study.  
  
Before taking any medicines besides the study drug, you must first ask the study doctor. These medicines may be ones that are ordered by a doctor. They may also be drugs like allergy medicines, cough and cold medicines and pain relievers, or they may be vitamins, herbs and minerals. The use of any investigational or antitumor therapies (other than eribulin and cyclophosphamide given as part of the study) is prohibited. Only you, the study subject, can take the study drug.
Clinical trial: NCT01554371
Section: Participant's Rights
Subsections: What Are My Rights If I Take Part In This Study?

Taking part in this study is your choice. You may choose either to take part or not to take part in the study. If you decide to 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 our institution. We will tell you about new information or changes in the study that may affect your health or your willingness to continue in the study. In the case of injury resulting from this study, you do not lose any of your legal rights to seek payment by signing this form.
Clinical trial: NCT01554371
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: What Side Effects Or Risks Can I Expect From Being In The Study?|Risks Of Eribulin: Common Side Effects:|Less Common Side Effects:|Risks Of Cyclophosphamide:|Other Risks Medications:|Radiation (X-Ray) Risks:|Ct And Pet/Ct Scan Risks:|Pregnancy Risks:|Unknown Risks:|What Happens If I Am Injured Because I Took Part In This Study?|Risks|Risks|Risks|Risks

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You may have side effects while on the study. Everyone taking part in the study will be watched carefully for any side effects. However, doctors don't know all the side effects that may happen. Side effects may be mild or very serious. Your health care team may give you medicines to help lessen side effects. Many side effects go away soon after you stop taking the study drugs. In some cases, side effects can be serious, long lasting, or may never go away. There is also a risk of death. You should talk to your study doctor about any side effects you experience while taking part in the study.

Decreased white blood cells (may increase chance of infection)
Decreased red blood cells (may cause weakness and tiredness)
Fatigue Hair loss Peripheral neuropathy (a form of damage to the nerves supplying the hands and feet, which leads to numbness or the feeling of "pins and needles" and/or impairment of muscle strength in the hands and feet)
Nausea Constipation

Eyes watering  
Upset Stomach/abdominal pain Inflammation or ulcers in the mouth (stomatitis)
Dry mouth Fluid retention Upper respiratory tract infection Low potassium in the blood (can cause constipation, weakness, and abnormal heart rhythms)
Muscle spasms, muscular weakness Change in taste Dizziness
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Insomnia Depression Rash Liver function test changes

Decrease in bone marrow function (resulting in lower level of blood cells)
Low levels of all blood cells (white blood cells, red blood cells, platelets)
Liver function test changes Inability to have children Rash Skin pigmentation changes Nail changes Stevens-Johnson syndrome (severe reaction that includes a painful rash that spreads and blisters, causing the top layer of skin to die and shed)
Congestive heart failure Infusion-related symptoms such as fever, chills, rigors, headache Abdominal pain Nausea Vomiting Diarrhea Inflammation or ulcers in the mouth and digestive tract (mucositis)
Hair loss Anorexia Pain Irritation of the bladder, which causes pain and can result in blood in the urine Scarring of the bladder Inflammation and pain in the urinary tract Kidney damage Stomach flu Inflammation and scarring of the lungs
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Jaundice Infections Secondary cancer Anaphylaxis (a severe, whole-body allergic reaction, which may require immediate medical attention)
SIADH (Excessive water retention that may cause electrolytes in your blood to fall to low levels)
General feeling of being sick (Malaise)
Lack of energy or strength
Additional information on cyclophosphamide (Cytoxan®) may be found in the approved package insert.

Before taking any over the counter medicines, herbal products, vitamins, food supplements, or any other types of special products while participating in this study, please discuss this with the study doctor who will tell you whether it is appropriate to start or continue taking these medicines. You should also talk to the study doctor before taking any medicines other doctors may have prescribed for you. This is to ensure that there are no harmful interactions between the study drug and any other medicines you are taking. Your study doctor may need to change or discontinue these for the duration of the study.

The amount of radiation you will be exposed to is relatively small. Such doses of radiation may be potentially harmful, but the risks are so small that they are difficult to measure. If you have already had many x-rays, you should discuss this with the researchers before agreeing to be in the study.

CT scans involve the risks of radiation (see above). In addition, if contrast material is used, there is a slight risk of developing an allergic reaction, from mild (itching, rash) to severe (difficulty breathing, shock, or rarely, death). The contrast material may also cause kidney problems, especially if you are dehydrated or have poor kidney function. The study doctors will ask you about any allergies or related conditions before the procedure. If you have any of these problems, you may not be allowed to have a CT scan.  
  
Having a CT scan may mean some added discomfort for you. In particular, you may be bothered by feelings of claustrophobia when placed inside the CT scanner, or by lying in one position for a long time. If contrast material is used, you may feel discomfort when it is injected. You may feel warm and flushed and get a metallic taste in your mouth. Rarely, the contrast material may cause nausea, vomiting or a headache.

The effects of the study drugs (eribulin and cyclophosphamide) on an unborn child are currently unknown. Therefore it is important that you take measures to avoid becoming pregnant while participating in the study. If you are pregnant, breast-feeding, or if you are not planning to take precautions against pregnancy, you are not allowed to take part in this study. If you are a woman who is not menopausal, a pregnancy test will be performed prior to study start. You should discuss any pregnancy plans with your study doctor before you are registered in this study. Additionally you must agree to use medically acceptable contraception as suggested by your study doctor for the time you are receiving the study drugs. If it is possible for you to become pregnant, you must agree to use two highly effective forms of birth control - one of which must be a barrier method (for example, use of a spermicide, an intrauterine device (IUD) or oral contraceptive, plus a barrier method such as a condom, diaphragm or cervical cap). Oral contraception must not be used alone. You and your partner must use adequate birth control from at least the first day of your last normal menstrual period before you take a study drug, and should continue until 30 days after the last dose of study drug.  
The only subjects who will be exempt from the birth control requirement are those who are unable to become pregnant:
Women who had hysterectomy (uterus removed), bilateral oophorectomy (both ovaries removed), bilateral tubal ligation and documentation of the procedure.  
Postmenopausal women in the appropriate age group who had their last period more than 1 year before start of the study treatment.  
If your partner had a vasectomy more than 3 months ago and a follow-up check showed zero sperm count, then you do not need other birth control.
If you are abstinent (no sexual intercourse), you must agree to use an acceptable method of birth control if you become sexually active during the study. If you become pregnant during the study or think that you might be pregnant, you must notify the study doctor immediately.

The experimental treatments may have side effects that no one knows about yet. The researchers will let you know if they learn anything that might make you change your mind about participating in the study. For more information about risks and side effects, ask your study doctor.

It is important that you tell your study doctor, Hope Rugo, M.D., if you feel that you have been injured because of taking part in this study. You can tell the doctor in person or call him/her Treatment and Compensation for Injury: If you are injured as a result of being in this study, the University of California will provide necessary medical treatment. The costs of the treatment may be billed to you or your insurer just like any other medical costs, or covered by the University of California, depending on a number of factors. The University does not normally provide any other form of compensation for injury. For further information about this, you may call the office of the Committee on Human Research at 415-476-1814.

The greatest risk to you is the release of information from your health records. We will do our best to make sure that your personal information will be kept private. The chance that this information will be given to someone else is very small.

The greatest risk to you is the release of information from your health records. We will do our best to make sure that your personal information will be kept private. The chance that this information will be given to someone else is very small. Genetic information that results from this study does not have medical or treatment importance at this time. However, there is a risk that information about taking part in a genetic study may Consent Form 06-27--2016 Page 16 of 19UCSF-CC\# 11996  
  
influence insurance companies and/or employers regarding your health. To further safeguard your privacy, genetic information obtained in this study will not be placed in your medical record. Taking part in a genetic study may also have a negative impact or unintended consequences on family or other relationships. If you do not share information about taking part in this study, you will reduce this risk. Although your name will not be with the sample, it will have other facts about you such as age, sex, ethnicity and treatment. These facts are important because they will help us learn if the factors that cause cancers to occur or get worse are the same or different based on these facts. Thus it is possible that study finding could one day help people of the same race, ethnicity, or sex as you. However, it is also possible through these kinds of studies that genetic traits might come to be associated with your group.

The greatest risk to you is the release of information from your health records. We will do our best to make sure that your personal information will be kept private. The chance that this information will be given to someone else is very small.

The greatest risk to you is the release of information from your health records. We will do our best to make sure that your personal information will be kept private. The chance that this information will be given to someone else is very small. Genetic information that results from this study does not have medical or treatment importance at this time. However, there is a risk that information about taking part in a genetic study may Consent Form 06-27--2016 Page 16 of 19UCSF-CC\# 11996  
  
influence insurance companies and/or employers regarding your health. To further safeguard your privacy, genetic information obtained in this study will not be placed in your medical record. Taking part in a genetic study may also have a negative impact or unintended consequences on family or other relationships. If you do not share information about taking part in this study, you will reduce this risk. Although your name will not be with the sample, it will have other facts about you such as age, sex, ethnicity and treatment. These facts are important because they will help us learn if the factors that cause cancers to occur or get worse are the same or different based on these facts. Thus it is possible that study finding could one day help people of the same race, ethnicity, or sex as you. However, it is also possible through these kinds of studies that genetic traits might come to be associated with your group.
Clinical trial: NCT01554371
Section: Procedures
Subsections: What Will Happen If I Take Part In This Research Study?|Before You Begin The Main Part Of The Study...|During The Main Part Of The Study...|Study Drug Administration:|Procedures That Are Part Of Regular Cancer Care:|Procedures That Are For Research Purposes Only: Ekg (Once; Cycle 1)|Bone Scan:|Ct Or Pet/Ct Scan:|Questionnaires (Neuropathy And Quality Of Life (Qol)):|Blood Samples For Research:|Archival Tumor Tissue Samples For Research (Optional):|Blood Sample For Future Genetic Research (Optional):

Each study visit may last between 3 to 6 hours depending on the particular procedures. The first day of the study drug dose will last over 8 hours due to the pharmacokinetics (PK) blood samplings.

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You will need to have the following exams, tests or procedures to find out if you can be in the main part of the study. These exams, tests or procedures are part of regular cancer care and may be done even if you do not join the study. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor.  
Medical history and physical exam Review of any medications you are currently taking or have taken within the last 30 days Radiographic studies which may include a CT scan (to monitor the cancer in your organs), PET scan, or bone scan (if your cancer has spread to your bones)
Other radiology tests may need to be done depending on your type of cancer Electrocardiogram (EKG): Done to monitor how your heart is working Laboratory/blood tests: Routine tests done to see if your kidney, liver, and other organs are working well Pregnancy test (if you are a female of childbearing age)
Research blood tests

If the exams, tests and procedures show that you can be in the main part of the study, and you choose to take part, then you will need to have the tests and procedures described below.

You will receive treatment with eribulin and cyclophosphamide as described below. The same treatment will be repeated every 3 weeks (21-days). This 3-week period is called a treatment cycle. Cyclophosphamide is injected into a vein on the first day (Day 1) of each cycle. The injection will take approximately 60-120 minutes. The exact dose of cyclophosphamide you receive will also be calculated based on your weight and height. You will also receive eribulin. Eribulin is injected into a vein on Day 1 and Day 8 of each cycle. The injection will take approximately 2-5 minutes. The exact dose of eribulin you receive will also be calculated based on your weight and height. At the beginning of the study (the Phase Ib portion), the first group of patients will be treated with a lower dose of study drug. If this low dose causes no or minimal side effects, new patients enrolled in the study will be given a slightly higher dose. Additional patients will be given higher doses until we have determined the highest dose that can be given without severe side effects; patients in the second part of the study (Phase II portion) will receive this highest dose.  
  
Neither you nor your doctor can choose the group you will be in. You can ask your doctor what group you will be in and what dose of study drug you will be receiving.

Physical exam (once per cycle) Performance score: You will be asked questions about your daily activities to evaluate your level of daily function.  
Laboratory/blood tests (twice per cycle in the Phase Ib portion, and twice per cycle in Cycle 1 and Cycle 2, then once per cycle in Cycle 3 and beyond in the Phase II portion)
CT, PET/CT, bone scan, and/or other radiology tests (every 6 weeks in the Phase Ib portion, and every 9 weeks in the Phase II portion)

Blood samples for Pharmacokinetic (PK) tests (Cycle 1): PK blood samples will be collected over an 8-hour period at the following time points: before you receive the study drug infusion (pre-dose), at the end of your study drug infusion, and then 15 minutes, 30 minutes, 1, 2, 3, 4, 6 and 8 hours following your infusion.  
Blood sample for Pharmacogenomic tests (once; before your first treatment)
Blood samples for measuring circulating tumor cells (CTCs) (Cycle 1 and possibly Cycle 2, depending on the results from your Cycle 1 test)
Archival tumor tissue (this is optional - permission is given at the end of this form) Neuropathy assessment (before your first treatment, then once per cycle beginning with cycle 2)
Neuropathy questionnaire (before your first treatment, then once per cycle beginning with cycle 2)
Quality of Life (QOL) questionnaire (before your first treatment, then at 6 weeks, 3 months, 12 months, 18 months, 24 months, and/or at study termination )

A bone scan is a test that makes detailed images of your bones and any tumors on them. Before the bone scan a small amount of radioactive substance is injected into your vein. About 3 hours later you will lay on a table under a machine which will make an image of your bones. The test itself will take about 1 hour, but the whole process takes up to 4 hours.

You will have a computerized tomography (CT) scan or positron emission tomography/CT (PET/CT) scan to check the status of your tumor. These scans use special x-ray equipment to make detailed pictures of body tissues and organs. You may first be injected with contrast material (iodine dye and/or radioactive substance). This contrast material makes your tissues and organs more visible in the pictures. You will be asked to rest for about 30 minutes while the contrast material circulates throughout your body. For the scan, you will need to lie still on a table inside a large doughnut-shaped machine. The table will move and the machine will make clicking and whirring noises as the pictures are taken. Each scan will take between 15 minutes to an hour.  
EKG (electrocardiogram):
An EKG records the natural electrical activity of your heart. You will lie down, and wires or "leads" will be attached to your chest with an adhesive. You will be asked to lie still while the machine prints out an electrical "picture" of your heart activity. The EKG takes about 15 minutes.

Because the study drug eribulin may potentially cause nerve damage, the study doctors will assess you for any nervous system changes throughout your participation in the study. This will be done by filling out these two questionnaires. These are standard questionnaires that are commonly used by health care professionals.

This includes Pharmacogenomic (PG), Pharmacokinetic (PK), and circulating tumor cell (CTC) tests. These tests are done to look for the presence or absence of certain genetic material (DNA or RNA) and proteins in your blood. This genetic material and protein are referred to as "biomarkers". These biomarkers may come from healthy cells or from cancer cells circulating in your blood. Studying these biomarkers may help us understand why different people respond differently to the study drugs (for example how it is stored, broken down, and excreted from the body, or why some people respond favorably to the drugs and some don't). No more than 2 tablespoons will be taken at any one time.

This tissue will be taken from a biopsy or surgery that was performed to diagnose your cancer. You do not need to undergo any extra procedure to donate this sample. Only extra tissue (tissue that is not needed to plan your care and which would normally be discarded) will be used to perform these research tests. Research tests performed on this tissue will involve looking for biomarkers (similar as for the blood samples above)

You may be asked to donate a blood sample (1-2 tablespoons) before the start of the treatment for future genetic testing. This sample is optional and will be discussed in greater detail at the end of this consent.
Clinical trial: NCT01554371
Section: Purpose of Research
Subsections: Why Is This Study Being Done?

The purpose of this study is to test the safety of eribulin (Halaven™) and cyclophosphamide
(Cytoxan®) given together at different doses. We want to find out what effects, good and/or bad, these drugs have on you and your cancer. Eribulin is a drug that has been approved by the U.S. Food and Drug Administration (FDA) for breast cancer that has spread to other parts of the body. Cyclophosphamide has been approved for different types of cancers (including breast cancer). However, the combination of eribulin and cyclophosphamide is considered experimental; that means this combination has not been approved by the FDA. The funding for this study is provided by Eisai Inc., the maker of eribulin.
Clinical trial: NCT01554371
Section: Withdrawal from Study
Subsections: Can I Stop Being In The Study?

Yes. You can decide to stop at any time. Tell the study doctor if you are thinking about stopping or decide to stop. He or she will tell you how to stop your participation safely. It is important to tell the study doctor if you are thinking about stopping so any risks from the study drugs can be evaluated by your doctor. Another reason to tell your doctor that you are thinking about stopping is to discuss what follow-up care and testing could be most helpful for you. The study doctor may stop you from taking part in this study at any time if he/she believes it is in your best interest, if you do not follow the study rules, or if the study is stopped.