Download Phase II Feasibility Trial Incorporating Bevacizumab into Dose

IRB Approval _________
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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.
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Participant Initials_____
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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
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Participant Initials_____
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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.
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Participant Initials_____
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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
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Participant Initials_____
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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
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 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)
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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
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Participant Initials_____
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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
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Infrequent:
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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
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Participant Initials_____
IRB Approval _________
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CALGB 40504
Southeast Cancer Control Consortium Consent Form
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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
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Participant Initials_____
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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
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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.
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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:
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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
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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.
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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.
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Version: Activation 6/30/06
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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.
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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
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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.
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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)
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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.
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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 ___________
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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 __________
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