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IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Phase II Feasibility Trial Incorporating Bevacizumab into Dose Dense Doxorubicin and Cyclophosphamide followed by Paclitaxel in Patients with Lymph Node Positive Breast Cancer What is a research study? You are being asked to take part in this study because you have breast cancer that has spread to your lymph nodes. This is a clinical trial (a type of research study). Clinical trials include only patients who choose to take part. Please take your time to make your decision and discuss it with your friends and family. This is an important form. Please read it carefully. It tells you what you need to know about this study. If you agree to take part in this research study, you need to sign the form. Your signature means that you have been told about the study and what the risks are. Your signature on this form also means that you want to take part in this study. Why is this study being done? This research is being done because current treatment does not help everyone with breast cancer. Cancers must stimulate the growth of new blood vessels in order to continue growing. This process is called ‘angiogenesis’. New drugs may treat cancers by blocking these new blood vessels from growing in the tumor. This study is testing a new drug called Bevacizumab that affects tumor blood vessels. Bevacizumab (Avastin is the brand name) is an FDA approved medication for use along with chemotherapy in patients with newly diagnosed colorectal cancer leading to improved survival compared to chemotherapy by itself. The addition of bevacizumab to chemotherapy in patients receiving initial chemotherapy for recurrent breast cancer increased response rates and time to progression (how long the cancer remained under control). Longer follow-up is needed to see if bevacizumab improves the overall survival of women with recurrent breast cancer. Bevacizumab is the common name for the commercial drug Avastin. The bevacizumab used in this study, however, is for use in research studies only and may be made at locations different from those where Avastin is made. Although some differences may exist, bevacizumab for research use and the commercial drug, Avastin, are manufactured by a similar process, meet similar standards for final product testing and are expected to be very similar in safety and effectiveness. It is unknown how to best use Bevacizumab in combination with chemotherapy for patients with newly diagnosed breast cancer. This purpose of this study is to examine whether the use of bevacizumab along with chemotherapy drugs commonly used in treating newly diagnosed patients with breast cancer (in this study doxorubicin and cytoxan) is safe. Specifically, this study will determine if adding bevacizumab increases the effect of chemotherapy on heart function. 6/30/06 Page 1 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form How many people will take part in the study? About 200 people will take part in this study. What is involved in this study? You will have a full medical history and physical examination taken along with blood and urine tests, chest x-ray, an electrocardiogram (a test that records the electrical activity of your heart), a MUGA or echocardiogram (a test that learns the function of your heart), a mammogram, and other tests that the doctor might feel are needed to fully learn about your disease and see if you can be on this study. Some of these tests would be done even if you do not take part in this study. Routine Tests Blood and urine tests Chest x-ray Electrocardiogram before starting chemotherapy MUGA or echocardiogram before starting chemotherapy Test Specific to this Study Urine tests – about every 8 weeks during treatment Electrocardiogram - four times during the first year after you begin treatment MUGA or echocardiogram - four times during the first year after you begin treatment Please see the Study Plan on the last page of this form. You will be registered into one of the study groups described below. Which regimen you receive will depend on when you are registered to the study. Your doctor will tell you which regimen you will receive. Treatment Groups Group A: You will receive Adriamycin®, Cytoxan® (AC), and bevacizumab (a research drug that inhibits the formation of blood vessels) by vein over about one hour one day every two weeks for a total of 4 treatments. After all treatment with AC plus bevacizumab is done, you will receive Taxol® and bevacizumab by vein over about 3-4 hours every two weeks for 4 treatments. After all treatment with Taxol® plus bevacizumab is done, you will receive bevacizumab by vein over about 30 minutes one day every two weeks for a total of 18 treatments. The first dose of bevacizumab will be given over about 90 minutes. If you do well with this first dose, the 6/30/06 Page 2 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form second dose will be given over one hour. If you do well with the second dose, other doses of bevacizumab will be given over about 30 minutes. Because the AC and Taxol® may lower the blood counts and increase your risk of infection, you will receive one of two growth factors called filgrastim (also called G-CSF or Neupogen®) or pegfilgrastim (also called Neulasta®) to help your body produce more white blood cells. Filgrastim is given as a shot under the skin once a day for ten days starting the day after AC or Taxol® was given. Pegfilgrastim is given as a single shot under the skin the day after AC or Taxol® was given. Your doctor will decide whether you will receive filgrastim or pegfilgrastim; either growth factor can be used in this study. You should discuss this choice with your doctor. You will not receive filgrastim or pegfilgrastim after treatment with bevacizumab alone. Each two week period is considered one cycle of treatment. The total duration of treatment will be about 12 months. All treatment will be done in a clinic or doctor’s office. Group B: You will receive Adriamycin®, Cytoxan® (AC), by vein over about 30 minutes one day every two weeks for a total of 4 treatments. After all treatment with AC is done, you will receive Taxol® and bevacizumab (a research drug that inhibits the formation of blood vessels) by vein over about 3-4 hours every two weeks for 4 treatments. After all treatment with Taxol® plus bevacizumab is done, you will receive bevacizumab by vein over about 30 minutes one day every two weeks for a total of 22 treatments. The first dose of bevacizumab will be given over about 90 minutes. If you do well with this first dose, the second dose will be given over one hour. If you do well with the second dose, other doses of bevacizumab will be given over about 30 minutes. Because the AC and Taxol® may lower the blood counts and increase your risk of infection, you will receive one of two growth factors called filgrastim (also called G-CSF or Neupogen®) or pegfilgrastim (also called Neulasta®) to help your body produce more white blood cells. Filgrastim is given as a shot under the skin once a day for ten days starting the day after AC or Taxol® was given. Pegfilgrastim is given as a single shot under the skin the day after AC or Taxol® was given. Your doctor will decide whether you will receive filgrastim or pegfilgrastim; either growth factor can be used in this study. You should discuss this choice with your doctor. You will not receive filgrastim or pegfilgrastim after treatment with bevacizumab alone. 6/30/06 Page 3 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Each two week period is considered one cycle of treatment. The total duration of treatment will be about 14 months. All treatment will be done in a clinic or doctor’s office. Regardless of which treatment group you are in, at the end of all chemotherapy (Adriamycin®, Cytoxan®, and Taxol®), you may also get hormonal therapy if your tumor is estrogen or progesterone receptor (ER+ or PR+) positive. Your doctor will talk this over with you. It is a part of standard care and not a part of the research question being asked in this study. If your surgery was a lumpectomy (removal of the tumor and surrounding tissue but not the entire breast), you will also get radiation therapy after your chemotherapy has ended. Radiation therapy may also be given for some patients who have had a mastectomy (removal of the entire breast and underlying tissue). Your doctor will talk this over with you. It is part of standard care and not a part of the research being asked in this study. How long will I be in the study? If you are registered to Treatment Group A: We think you will receive treatment in this study for a maximum of 12 months unless your disease progresses or side effects of treatment would make it unsafe for you to continue. If you are registered to Treatment Group B: We think you will receive treatment in this study for a maximum of 14 months unless your disease progresses or side effects of treatment would make it unsafe for you to continue. We would like to keep track of your medical condition for up to 3 years from the time you enter the study to look at the long-term effects of the treatment. Once you complete treatment, your doctor will see you at least every 3 months for the first 6 months. Your doctor will see you at least every 6 months thereafter until 3 years from study entry. Your doctor may decide to take you off this study if your disease does not improve or if side effects of treatment would make it unsafe to continue. You will be informed of new developments that may become available that might affect your willingness to continue treatment. You may stop participating at any time. However, if you decide to stop participating in the study, we encourage you to talk to your doctor first. What side effects or risks can I expect from being in the study? While on the study, you are at risk for the following side effects. Drugs used is this study may cause some, all or none of the side effects listed. You should discuss these with your doctor. There may also be other side effects that we cannot predict or are 6/30/06 Page 4 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form unforeseen or unexpected. Other drugs will be given to make side effects less serious and less uncomfortable. Many side effects go away shortly after the drugs are stopped, but in some cases side effects can be serious, long-lasting, permanent or lifethreatening. Death is rare, but possible. Your doctor will check you closely to see if any of these side effects are occurring and routine blood tests will be done to monitor the effects of treatment. Risks and side effects related to the drugs we are studying include: Adriamycin® plus Cytoxan® (AC) with filgrastim or pegfilgrastim More Likely: Nausea and vomiting Loss of appetite Heartburn Hair loss Lowering of your blood cell counts that could cause infection, easy bruising and bleeding or anemia Less Likely: Sores in mouth Tingling and redness in the hands and feet Change in color or loosening of fingernails and toenails Inflammation of damage to the skin around the IV tubing Bladder inflammation Bone or joint pain Cramps in the legs or back Rare: Heart damage Bevacizumab may increase the risk of heart damage Increased risk of blood cancer called leukemia Taxol® with filgrastim or pegfilgrastim More Likely: Lowering of your blood cell counts that could cause infection, easy bruising and bleeding or anemia Mild to severe allergic reaction Numbness and pain of the hands and feet that sometimes worsens with additional treatment and may not disappear after the drug is stopped Hair loss 6/30/06 Page 5 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Muscle weakness and muscle loss Muscle and joint aches Less Likely: A slowing of the heart rate Irregular heartbeats Nausea and/or vomiting Diarrhea Sores in the mouth or throat Fatigue Lightheadedness Headaches A sensation of flashing lights or spots Changes in kidney function tests An increase in triglyceride (blood lipid) levels Changes in liver enzymes Confusion or mood changes Skin irritation and swelling if the drug leaks from the vein into which it is being injected into the surrounding skin Rare: Liver damage or failure Seizures Bevacizumab Likely: High blood pressure (including dangerously high blood pressure called hypertensive crisis) Shortness of breath Abnormal levels of protein in the urine (which may indicate kidney damage) Mild to moderate bleeding in the gastrointestinal tract Nose bleeds Sores in mouth and/or throat Changes in taste Skin changes (including itching, rash, discoloration, ulcers or peeling) 6/30/06 Page 6 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Less Likely: Clots in the arteries, including stroke or heart attack: When several studies were looked at together, problems due to clots in arteries were increased about two-fold in patients receiving chemotherapy plus bevacizumab compared to chemotherapy alone. Patients who were elderly and had a past history of clots in the arteries appeared to be at greater risk for these problems. These conditions can be life-threatening or fatal. Lowered white blood cell count (may make you more likely to get infections) Lowered platelet count that might interfere with clotting (may make you more likely to bruise or bleed) Lowered sodium and/or potassium levels that might make you feel weak or dizzy Changes in blood tests that indicate possible damage to the kidney Gastrointestinal upset (which may include gas, constipation, diarrhea, nausea, vomiting, loss of appetite, heartburn or dry mouth) Cough Watery eyes Voice changes (hoarseness) Headache Pain Weight loss Confusion Poor coordination and balance Frequent urination (peeing) Tiredness or weakness Flu-like symptoms, such as fever, chills, stiffness, and muscle aches Impaired fertility Rare, but Serious Coughing up blood Worsening of any fluid within the tissues of the lung or lung problems Delay in wound healing or breakdown of a wound that had healed Heart problems (including irregular heartbeats, changes in blood pressure, fluid collections surrounding the heart, chest pain, and possibly heart attack or heart failure) Bleeding in various parts of the body including the brain (stroke), the lungs (especially in lung cancer patients), the stomach, and the colon: This bleeding can lead to disability or death. Blood clots in the legs, lungs or abdomen Serious stomach and/or bowel problems (such as the breakdown of tissue at the site where bowel is re-attached after removal of a tumor, formation of a hole in the stomach or bowel wall) which can lead to serious infection and require surgery to repair 6/30/06 Page 7 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Bowel perforation: an opening occurs in the bowel wall, allowing bowel contents to spill into the abdomen Breakdown in the surgical connection between two pieces of bowel (Bowel anastomotic dehicense): This event can be life-threatening. Blockage of the intestines and breakdown of the tissue in the intestines Reversible changes in liver function tests that may indicate liver damage Damage to the kidney Allergic reaction Infection Reversible Posterior Leukoencephalopathy Syndrome (RPLS) or similar leukoencephalopathy syndrome: RPLS is a medical condition related to leakiness of blood vessels in the brain and can cause confusion, blindness or vision changes, seizure and other symptoms, as well as changes in brain scans. This condition is usually reversible, but in rare cases, it is potentially life-threatening and may have a long-term effect on brain function. NOTE: Bevacizumab is the common name for the commercial drug Avastin. The bevacizumab used in this study, however, is for use in research studies only and may be made at locations different from those where Avastin is made. Although some differences may exist, bevacizumab for research use and the commercial drug, Avastin, are manufactured by a similar process, meet similar standards for final product testing, and are expected to be very similar in safety and effectiveness. NOTE: Problems due to blood clots in the arteries were seen in about 2.9% of patients 65 years or older receiving chemotherapy alone, and about 8.5% of patients in this age group treated with chemotherapy plus bevacizumab. Elderly patients with a past history of clots in arteries appeared to be at even higher risk, although further study is required before an estimate of the risk can be provided. Tamoxifen: Tamoxifen may cause changes in the lining of the uterus (endometrium). In addition, in a few patients tamoxifen has been associated with an increased risk of uterine cancer. Of course, if you have had a total hysterectomy, there is no risk of getting uterine cancer. Tamoxifen side effects that frequently happen are: Frequent: Hot flashes A feeling of being sick to the stomach Throwing up Menstrual irregularities including vaginal discharge, bleeding, and dryness 6/30/06 Page 8 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Infrequent: Abnormal occurrence of blood clots Women taking tamoxifen may be at a slightly higher risk for getting cataracts (a clouding of the lens inside the eye). As women age, they are more likely to get cataracts whether or not they take tamoxifen. Cataracts may lead to poor vision. Tamoxifen can raise sensitivity to blood thinners such as coumadin. Anastrozole Common side effects (happens in greater than 5% of patients) Hot flashes Fluid retention (swelling in legs, puffiness around the eyes, and generalized swelling) Pain (in chest, bone, and pelvic areas, in legs and joints, and at the tumor site) Headache Dizziness Depression Rash Feeling sick to the stomach Throwing up Loose stools Abdominal pain Loss of appetite Dry mouth Muscle weakness Tingling of the arms and leg Shortness of breath Cough Inflammation of the throat area Less common side effects (happens in 2-5% of the patients) High blood pressure Inflammation of the veins Problems sleeping Confusion Anxiety Fever Nervousness Feeling out of sorts Hair thinning Rash 6/30/06 Page 9 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Breast pain Weight loss Infections (upper and lower respiratory tract and urinary tract) Loss of energy Lowered blood counts that can lead to infection, bleeding, and bruising Muscle and joint pain Neck pain Inflammation of the nose and throat areas Flu-like symptoms Infection Possible fracture Letrozole Common side effects (happens in more than 10% of patients) Hot flashes Headache Tiredness Feeling sick to the stomach Pain (in chest, rib, and back areas, in legs and joints, muscles, and at the tumor site) Shortness of breath Cough Less common side effects (happens in 2-9% of patients) Chest pain Fluid retention (swelling in legs, puffiness around the eyes, and generalized swelling) High blood pressure Problems sleeping Dizziness Depression and anxiety Rash Loss of hair Breast pain Throwing up Trouble passing stool Loose stools Abdominal pain Loss of appetite Weight loss or weight gain Increase in cholesterol levels Stomach discomfort after eating 6/30/06 Page 10 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Rare side effects (happens in less than 2% of patients) Blood clots Heart problems (heart attack, coronary artery disease, etc.) Exemestane Common side effects (happens in more than 9% of patients) Hot flashes Fatigue Pain (in chest, rib, and back areas, in legs and joints, and at the tumor site) Problems sleeping Depression or anxiety Difficulty with breathing Feeling sick to the stomach Decreased number of a type of blood cell called lymphocytes, which could increase your chance of infection Less common side effects (happens in about 3 to 9% of patients) Dizziness Sweating Fluid retention (swelling in legs, puffiness around the eyes, and generalized swelling) High blood pressure Burning or prickling sensations Skin rash Itching Flu-like symptoms Fever Coughing Infections (upper and lower respiratory tract and urinary tract) Weakness Weight gain Throwing up Loose stools Abdominal pain Loss of appetite Increased appetite Constipation Intestinal or stomach discomfort Headache Hair loss Confusion Decreased sensitivity to stimuli 6/30/06 Page 11 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Rare, but Serious Changes in blood test results that indicate problems with liver and/or kidney function Exemestane causes breaks in the genetic material (DNA) of human cells grown in the laboratory. Studies to test whether exemestane causes cancer in rats and mice have not been completed yet, but it is known that drugs that cause breaks in DNA sometimes cause cancer in people Radiation therapy: During radiation therapy, you may get the following side effects: Redness and irritation of the skin in the area being treated After ending radiation therapy, you may get none, some or all of the following side effects: Tanning and dryness of the skin in the treatment area Swelling of the arm Chest or breast discomfort Less common side effects may be: Lung or heart injury Broken rib(s) Reduced arm motion Start of another cancer Risks related to fertility and pregnancy: The drugs in this study may affect the way a woman’s ovaries work and her ability to get pregnant. The drugs in this study can affect an unborn baby. Therefore, women should not become pregnant and men should not father a baby while on this study. Both men and women must use a reliable method of birth control while participating in this study. Reliable methods of birth control are considered to be: abstinence (not having sex), tubal ligation, hysterectomy or vasectomy of the partner (with confirmed negative sperm counts) in a monogamous relationship (same partner). An acceptable, although less reliable method involves the careful use of condoms and spermicidal foam or gel and/or cervical cap or sponge. Both male and female patients should ask about counseling and more information about preventing pregnancy. Female patients who feel they might be pregnant, even though they practiced birth control, must notify the study doctor immediately. A pregnancy test may be performed. Male patients should also inform the study doctor immediately if their sexual partners become pregnant while the patient is receiving treatment. Women should not breastfeed a baby while on this study. Pregnant women and nursing mothers are excluded from participation in this study. If a woman becomes pregnant, she will be withdrawn from the study. If a man fathers a child, there may be potential risk to the unborn baby; therefore, female sexual partners of men on treatment should use an adequate form of birth control. 6/30/06 Page 12 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form If you are able to become pregnant, a blood test will be performed before the study to insure you are not pregnant. Because the drug in this study can possibly affect an unborn baby and infants, you should not become pregnant or father a baby or breast feed while you are on this study. Also, bevacizumab remains in your body for weeks to months, you should continue to use adequate contraceptive measures and avoid nursing a baby for at least 3-4 months after your last dose of bevacizumab, although the exact duration of bevacizumab remaining in the body is not predictable for each individual patient. If you have any questions about these issues, or have questions about preventing pregnancy, please discuss them with your doctor. For more information about risks and side effects, ask the researcher or contact your local doctor. Will I benefit from taking part in the study? If you agree to take part in this study, there may or may not be direct medical benefits to you. The possible benefits of taking part in the study may be the same as receiving doxorubicin, cyclophosphamide, and paclitaxel without being in the study. The benefits of adding bevacizumab to your treatment is unknown. We hope the information learned from this study will benefit other patients with breast cancer in the future. What other choices do I have if I do not take part in this study? Instead of being in this study, you have these options: Standard chemotherapy or hormonal therapy No treatment at this time, with care to help you feel more comfortable. You may receive doxorubicin, cyclophosphamide, and paclitaxel at this medical center and at other medical centers, even if you do not take part in this study. Will my medical information be kept private? This study is being conducted by the Eastern Cooperative Oncology Group (ECOG). ECOG is a cancer group that conducts studies for the National Cancer Institute. Your doctor is a member of ECOG or another group that is participating in this study. To help protect your privacy, ECOG has obtained a Confidentiality Certificate from the Department of Health and Human Services (DHHS). With this Certificate, ECOG cannot be forced (for example, by court subpoena) to disclose information that may identify you in any federal, state or local civil, criminal, administrative, legislative or other proceedings. Disclosure will be necessary, however, upon request of DHHS for audit or program evaluation purposes. You should understand that a Confidentiality Certificate does not prevent you or a member of your family from voluntarily releasing information about you or your 6/30/06 Page 13 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form involvement in this research. Note, however, that if an insurer or employer, learns about your participation and obtains your consent to receive research information, then ECOG may not use the Certificate of Confidentiality to withhold this information. This means that you and your family must also actively protect your privacy. Finally, you should understand that your doctor and ECOG are not prevented from taking steps, including reporting to authorities, to prevent serious harm to yourself or others and the Certificate does not prevent the review of your research records under some circumstances by certain organizations for an internal program audit or evaluation. Organizations that may inspect and/or copy your research records for quality assurance and data analysis include groups such as: We will do our best to make sure that the personal information in your medical record will be 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. A record of your progress will be kept in a confidential form at your hospital or doctor’s office where you receive treatment. Organizations that may inspect and/or copy your research and medical records (blood samples, x-rays, scans, pathology slides, etc.) for quality assurance, research, and data analysis include groups such as: Southeast Cancer Control Consortium (SCCC) Operations Office Cancer and Leukemia Group B (CALGB) Eastern Cooperative Oncology Group (ECOG) National Cancer Institute (NCI) and its representatives Food and Drug Administration (FDA) Office for Human Research Protections (OHRP) Institutional Review Board (IRB) at your hospital A qualified representative of Genentech, Inc., the maker of bevacizumab Possible other federal or state government agencies If your record is used or given out for governmental purposes, it will be done under conditions that will protect your privacy to the fullest extent possible consistent with laws relating to public disclosure of information and law-enforcement responsibilities of the agency. These agencies may review the research to see that it is being done safely and correctly. You authorize the use of clinical information contained in your records, but any publication which includes such information or data shall not reveal your name, show your picture or contain any other personally identifying information, except as otherwise required by law. 6/30/06 Page 14 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form What are the costs of taking part in this study? You and/or your health plan/insurance provider (Medicare should be considered a health insurance provider) will need to pay for some or all of the costs of treating your cancer in this study. Some health plans will not pay these costs for people taking part in studies. Check with your health plan or insurance company to find out what they will pay for. Taking part in this study may or may not cost your insurance company more than the cost of getting regular cancer treatment. You or your insurance carrier will be responsible for the costs of clinic visits, any hospital admissions, laboratory tests, xrays, scans, chemotherapy treatments, radiation treatments, and any other tests. Please ask your doctor about any added costs or insurance problems. The Division of Cancer Treatment and Diagnosis with the NCI will provide you with the research drug, bevacizumab, free of charge to all participants. If bevacizumab becomes commercially available for this indication, there is a remote possibility that you may be asked to purchase subsequent supplies. Your doctor will discuss this with you should this situation arise. For more information on clinical trials and insurance coverage, you can visit the National Cancer Institute’s Web site at http://cancer.gov/clinicaltrials/understanding/insurancecoverage. You can print a copy of the “Clinical Trials and Insurance Coverage” information from this Web site. You will not be paid to participate in this study. What happens if I am injured because I took part in this study? It is important that you tell your study doctor, _________________________ 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 at #____________________________. You will get medical treatment if you are injured as a result of taking part in this study. You and/or your health plan will be charged for this treatment. The study will not pay for medical treatment. Although no funds or monies have been set aside to compensate you in the event of injury or illness related to the study treatment or procedures, you do not waive any of your legal rights for compensation by signing this form. You or your insurance company will be charged for continuing medical care and/or hospitalization. What are my rights if I take part in this study? Taking part in this study is voluntary. You may choose to take part, not to take part, or 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 or result in any penalty or loss of benefits to which you are entitled. 6/30/06 Page 15 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Even after you agree to take part in this study, you may withdraw at any time. Before you withdraw, you should talk to one of the researchers or nurses involved. This will allow them to inform you of any medical problems that could result from stopping your treatment. You can choose to withdraw one of two ways. In the first, you can stop your study treatment, but still allow the study doctor to follow your care. In the second, you can stop your study treatment and not have any further contact with the study staff. Either way, there will be no penalty to you. Your decision will not affect your medical treatment or your relationship with those treating you or with this institution. If you withdraw from the study, you will still be offered all available care that suits your needs and medical condition. You are free to seek care from a doctor of your choice at any time. We will tell you about new information that may affect your health, welfare or willingness to stay in this study. You may be asked to sign another consent form in response to new information. Who can answer my questions about the study? For questions about the study or a research-related injury, contact your doctor, _________________, at # _____________________. You may ask your doctor for further information on the risks, benefits or alternative treatments. For questions about your rights as a research participant, contact the ___________________ Institutional Review Board (which is a group of people at the hospital in the community where you receive treatment who review the research to protect your rights) at # ____________________ (the office of __________________________). Will any of the samples (for example: tissue) taken from me be used for other research studies? About Using Tissue for Research To determine if you have cancer, your doctor performed a biopsy. ECOG would like to keep some of the tissue collected from your biopsy for future research. If you agree, this tissue will be kept and may be used in research to learn more about cancer and other diseases. This tissue will be given only to researchers approved by the Eastern Cooperative Oncology Group (ECOG). Any research done on the tissue also must be approved by the researcher’s Institutional Review Board. Your tissue may be helpful for research, whether you do or do not have cancer. The research that may be done with your tissue will probably not help you. It might help people who have cancer and other diseases in the future. Reports about the research done with your tissue will not be given to you or to your doctor. These reports will not be put into your health record. The research will not have an effect on your care. 6/30/06 Page 16 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Things to Think About The choice to let us keep the leftover tissue for future research is up to you. No matter what you decide to do, it will not affect your care, and you may still take part in the Eastern Cooperative Oncology Group study. If you decide now that your tissue can be kept for research, you can change your mind at any time. Just contact your study doctor and let him or her know that you do not want us to use your tissue. Then the tissue will no longer be used for research. In the future, people who do research may need to know more about your health. When the Eastern Cooperative Oncology Group gives them reports about your health, it will not give them your name. Sometimes tissue is used for genetic research (about disease that are passed on in families). Even if your tissue is used for this kind of research, the results will not be put into your health records. Your tissue will be used only for research, and it will not be sold. You will not be paid for allowing your leftover tissue to be used in research, even though the research done with your tissue may help to develop new products in the future. Similarly, there will be no cost to you for any tissue collected and stored by the Eastern Cooperative Oncology Group. It is possible that, at some time in the future, as part of deciding on which treatment to give you, a new test might become available that could be done on some of the tissue that is now thought of as “leftover.” This situation is unusual, but it could happen. In order to see that not all of this leftover tissue is used up, the Eastern Cooperative Oncology Group will take care to see that some of your cancer tissue is stored for 10 years so it is available if you or your doctors should need it. This will depend upon the amount of leftover tissue that is submitted for this study. However, there may not be any leftover tissue to store. Benefits The benefits of research using tissue include learning more about what causes cancer and other diseases, how to prevent them, how to treat them, and how to cure them. Risks There are very few risks to you. The greatest risk is the release of information from your health records. The Eastern Cooperative Oncology Group will protect your records so that your name will be kept private. The chance that this information will be given to someone else is very small. Making Your Choice Please read each sentence below and think about your choice. After reading each sentence, circle “Yes” or “No.” No matter what you decide to do, it will not affect your 6/30/06 Page 17 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form care. You can participate in the treatment part of the study without participating in all or part of the tissue research studies. If you have any questions, please talk to your doctor or nurse or call our Institutional Review Board at #__________________________. My tissue may be kept for use in future research to learn about, prevent, treat, or cure cancer. Yes No My tissue may be kept for use in future research about other health problems (for example: causes of diabetes, Alzheimer’s disease, and heart disease). Yes No My doctor (or someone from the Eastern Cooperative Oncology Group) may contact me in the future to ask me to take part in more research. Yes No Where can I get more information? You may call the National Cancer Institute’s (NCI’s) Cancer Information Service at: 1-800-4-CANCER (1-800-422-6237) or TTY: 1-800-332-8615 You may also visit the NCI Web site at http://cancer.gov For the NCI’s clinical trials information, go to: http://cancer.gov/clinicaltrials For the NCI’s general information about cancer, go to: http://cancer.gov/cancerinfo Cancer Fax includes NCI information about cancer treatment, screening, prevention, and supportive care. To obtain a contents list, dial 301-402-5874 or 800-624-2511 from a fax machine hand set and follow the recorded instructions. Participant Contract I have been offered the opportunity to ask questions about this study and all questions have been answered to my satisfaction. The contents of this form have been explained to me and I understand them. I agree to allow the research personnel specified above the access to my medical records. 6/30/06 Page 18 of 20 Participant Initials_____ IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form It may be necessary for my doctor to contact me at a future date regarding new information about the treatment I received; therefore I agree to notify my doctor of any change of address and/or telephone number. My signature below means that I have voluntarily agreed to participate in this research study. I will be given a copy of all 20 pages of this consent. I may also request a copy of the study (complete study plan). ______________ (Date) _________________________________ (Participant Signature) I certify that I have explained to the above individual the nature and purpose, the potential benefits, and possible risks associated with participation in the research study and have answered any questions that have been raised. ______________ (Date) 6/30/06 _________________________________ (Signature of Person Obtaining Consent) Page 19 of 20 IRB Approval _________ Version: Activation 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Consent Form Study Plan Register* You will receive Adriamycin®, Cytoxan®, (AC), and bevacizumab1 by vein over about 30 minutes one day every two weeks for a total of 4 treatments. 2 You will receive Taxol® and bevacizumab1 by vein over about 3-4 hours every 2 weeks for a total of 4 treatments. 2 You will receive bevacizumab1 by vein over 30 minutes one day every 2 weeks for a total of 18 treatments. 3,4 You will receive Adriamycin® and Cytoxan®, (AC) by vein over about 30 minutes one day every two weeks for a total of 4 treatments. 2 You will receive Taxol® and bevacizumab1 by vein over about 3-4 hours every 2 weeks for a total of 4 treatments. 2 You will receive bevacizumab1 by vein over 30 minutes one day every 2 weeks for a total of 22 treatments. 3,4 1 cycle or treatment = 2 weeks (14 days) 1 = The first dose of bevacizumab will be given over about 90 minutes. If you do well with this first dose, the second dose will be given over one hour. If you do well with the second dose, other doses of bevacizumab will be given over about 30 minutes. 2 = Because the AC and Taxol® may lower the blood counts and increase your risk of infection, you will receive either filgrastim (G-CSF or Neupogen®) or pegfilgrastim (Neulasta®) to help your body produce more white blood cells. Filgrastim is given as a shot under the skin once a day for ten days starting the day after AC or Taxol® was given. Pegfilgrastim is given as a single shot under the skin the day after AC or Taxol® was given. You will not receive filgrastim or pegfilgrastim after treatment withbevacizumab alone. 3 = At the end of all chemotherapy (Adriamycin®, Cytoxan®, and Taxol®), you may also get amoxifen, a hormonal therapy, for five years if your tumor is estrogen or progesterone receptor (ER+ or PR+) positive. If you are postmenopausal and your tumor is estrogen or progesterone receptor positive, you could get an anti-estrogen drug called an aromatase inhibitor (either anastrozole, letrozole or exemestane) for five years instead of tamoxifen. If you are postmenopausal and are taking tamoxifen, you will continue to take it for two to five years and then be able to take an aromatase inhibitor for an additional three to five years. Both tamoxifen and aromatase inhibitors are given by mouth each day; they have been proven helpful in lessening the risk of the return of breast cancer. Your doctor will talk this over with you. It is a part of standard care and not a part of the research question being asked in this study. 4 = If your surgery was a lumpectomy (removal of the tumor and surrounding tissue but not the entire breast), you will also get radiation therapy after your chemotherapy has ended. Radiation therapy may also be given for some patients who have had a mastectomy (removal of the entire breast and underlying tissue). * You will be registered into one of the study groups described above. Which regimen you receive will depend on when you are registered to the study. Your doctor will tell you which group you will receive. 6/30/06 Page 20 of 20 CALGB 40504 Southeast Cancer Control Consortium Withdrawal of Consent I, _____________________________, withdraw my consent to participate in this study and refuse to be followed and have clinical data collected from my medical records. Participant Name ______________________________ Study/ID #___________ (Please Print Name) Participant Signature ______________________________ Date ___________ Witness Signature ________________________________ Date ___________ 6/30/06 CALGB 40504 Southeast Cancer Control Consortium Withdrawal of Treatment Consent I, _____________________________, withdraw my consent for treatment on this study. Even though I withdraw my consent for treatment, I will continue to be followed and clinical data will be collected from my medical records. Participant Name ____________________________Study/ID #____________ (Please Print Name) Participant Signature _______________________________ Date __________ Witness Signature _________________________________ Date __________ 6/30/06