Download A Randomized Trial of Adjuvant Chemotherapy with Standard

IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
4/05
A Randomized Trial of Adjuvant Chemotherapy with Standard Regimens,
Cyclophosphamide, Methotrexate, and Fluorouracil – (CMF) or
Doxorubicin and Cyclophosphamide – (AC), Versus Capecitabine in Women
65 Years and Older with Node Positive or Node Negative Breast Cancer
What Is a Research Study?
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. Discuss it with your
friends and family.
4/02
You are being asked to take part in this study because you are a woman 65 years of age or
older with early stage breast cancer that has been removed by surgery.
4/02
You may be contacted by a Y-ME volunteer to discuss general aspects of this study and this
consent document. Medical questions about the treatment of your breast cancer should be
directed to the medical staff taking care of you.
4/02
4/02
4/02
11/02
Why Is This Study Being Done?
Breast cancer in women your age is a major health issue in the United States. Because very
few women 70 years of age and older participate in breast cancer treatment studies, there
is a lack of information about the risks and benefits of chemotherapy in this age group. In
patients in your age group, adjuvant chemotherapy may be less beneficial because older
patients may have more than one serious disease in addition to breast cancer. Your doctor has
discussed the risks, benefits and the uncertainties of adjuvant chemotherapy with you and
suggests that you consider participating in this clinical trial. Previous studies of metastatic
(cancer that had spread to other parts of the body) breast cancer, which included a small
percentage of women in your age group, indicated that the response to treatment and
tolerability of the side effects were similar in older and younger women.
The standard treatment is surgery, followed by adjuvant combination chemotherapy (adjuvant
means “in addition” to the surgery) and/or radiation therapy. If your cancer is responsive to
hormones, this is then followed by the hormonal therapy (blocks the hormones that are known
to stimulate the growth of cancer cells) with the drug tamoxifen, or letrozole or anastrozole for
5 years. Adjuvant combination chemotherapy for women who are less than age 65 with early
stage breast cancer is associated with significant improvements in both preventing the cancer
from returning and overall survival. It is not known if the same benefits apply to similar
women who are age 65 and older.
The purpose of this study is to compare the safety and effectiveness of standard adjuvant
combination chemotherapy using cyclophosphamide + methotrexate + 5-fluorouracil (CMF),
or doxorubicin (also called Adriamycin) + cyclophosphamide (AC), to the chemotherapy
drug capecitabine, in women 65 years of age and older. The study will also help gain more
information about the effects of each of the treatments on physical and emotional
well-being and how well the participants assigned to receive capecitabine follow the
treatment plan.
9/15/01
Page 1 of 11
Participant Initials _____
IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
Previous studies in patients with advanced breast cancer have shown that capecitabine
has the ability to shrink breast cancer. In previous studies which compared CMF to
capecitabine, it appeared that the capecitabine was at least as effective as CMF in
shrinking breast cancers.
Cyclophosphamide, methotrexate, 5-fluorouracil, and doxorubicin have been approved by
the Food and Drug Administration (FDA) of the United States for the treatment of breast
cancer. Capecitabine has been approved for the treatment of breast cancer that has spread to
other parts of the body and does not respond to other chemotherapy drugs. Its use as adjuvant
treatment for early stage breast cancer, as used in this study, is considered to be research.
How Many People Will Take Part in the Study?
Between 600 and 1,800 women will take part in this study.
What Is Involved in the Study?
You will be “randomized” into one of the treatment groups described below. Randomization
means that you are assigned to a group by chance. The treatment group you are assigned
to is chosen by a computer. Neither you nor your doctor will choose which group you will
be in. You will have an equal chance of being assigned to either group.
R
A
N
D
O
M
I
Z
E
Treatment A
CMF or AC
Treatment B
Capecitabine
Treatment A
If you are assigned to this treatment group, you and your doctor will decide whether you
will receive the CMF or the AC standard combination chemotherapy. These treatments are
given as outpatient treatment in the clinic.
4/02
9/05
If you choose CMF, you will be given a prescription for cyclophosphamide tablets, which
you will take by mouth, daily for 14 days. You will be asked to record each dose of
cyclophosphamide on a Cyclophosphamide Calendar every time your take it. You will be
given methotrexate and 5-fluorouracil through a vein over approximately 15-30 minutes on
days 1 and 8. This treatment will be repeated every 28 days. This 28 day period is called a
treatment cycle. You will receive 6 cycles (6 months) of this treatment.
9/15/01
Page 2 of 11
Participant Initials _____
IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
9/05
If you choose AC, you will be given doxorubicin and cyclophosphamide through a vein over
approximately 15-30 minutes on day 1, every 21 days. This 21 day period is called a treatment
cycle. You will receive 4 cycles (3 months) of this treatment.
Treatment B
If you are assigned to this treatment group you will be given a supply of capecitabine
tablets, which you will take at home, by mouth, twice daily for 14 days. This treatment will
be repeated every 21 days. This 21 day period is called a treatment cycle. You will receive
6 cycles (4 l/2 months) of this treatment. If you take antacids which contain aluminum
hydroxide or magnesium hydroxide (like Maalox®) they should not be taken within one hour
of taking the capecitabine. The study staff will give you additional instructions on how to take
the capecitabine.
5/15/06
All Treatment Groups
After you have completed the study treatment, if your breast cancer is the type that is
responsive to hormones your doctor may recomment hormonal therapy with tamoxifen,
anastrozole, exemestane or letrozole.
If your breast cancer is the type that is responsive to trastuzumab (also known as Herceptin®)
your doctor may recommend treatment with this drug.
Quality of Life
The researchers are also interested in learning if there are differences in the physical and
emotional well being of the women who receive Treatment A and Treatment B. Before you
are told about your treatment assignment, you will be given a quality of life questionnaire,
which you will fill out in the clinic and take home with you. About 2-3 days later a Research
Interviewer will contact you by telephone to collect your answers to the questionnaire. This
will take about 45 minutes. You will then be interviewed five more times: midway through the
study treatment, 1 month after you have completed the study treatment, and at months 12, 18,
and 24. These interviews will take about 35 minutes each time. The quality of life questionnaire
will be mailed to you before each telephone interview.
If you have difficulty hearing and cannot be interviewed by telephone, the questionnaires
may be filled out and mailed to the interviewer in addressed, stamped envelopes, which will
be sent to you.
You will be asked to fill out all of the quality of life questionnaires, even if you do not finish
the study treatment.
Capecitabine Adherence
Consistently following a medication schedule (known as drug adherence) may have a
relationship to the effectiveness of the medication. With the availability of more
chemotherapy drugs given by mouth, which patients can take themselves, it will be
important for doctors to understand any difficulties patients may have in following their
medication schedules.
9/15/01
Page 3 of 11
Participant Initials _____
IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
If you are assigned to receive capecitabine, and have agreed to participate in the quality
of life interviews, you will be asked to participate in the drug adherence portion of this
study. If you agree to participate, the capecitabine tablets will be given to you in special
bottles with an electronic device in the lid. The device will record the time that you open
and close the bottle. For this reason, we ask that you do not put the tablets into any
other bottle and that you do not open the capecitabine bottle unless you are taking a
tablet. Also, you should always replace the lid back on the bottle after each time you open
it. If you agree to participate you will be given detailed instructions on how to use the
special medication containers.
If you use a daily pill organizer you can still participate in the adherence portion of this
study. Please ask the study team for details.
I agree to participate in the quality of life telephone interviews. If I am assigned to receive
capecitabine, I also agree to participate in the adherence portion of this study.
_____ Yes
_____ No
_____ Initials
Testing and Follow-up
If you take part in this study, you will have the following routine tests and procedures
before the study treatment begins: you will be asked to give your medical history and have
a physical examination, blood tests, a chest x-ray, and a mammogram. If you are going to
receive the AC treatment, you will have a MUGA scan or an echocardiogram, which
measure your heart’s ability to pump.
During the time that you are receiving the study treatment, a physical examination and
blood tests will be done on day 1 of each treatment cycle. If you are receiving the CMF
treatment, blood tests will also be done on day 8 of each cycle. MUGA scans or
echocardiograms will be done, as your doctor feels necessary.
After the study treatment has been completed, the physical examinations will be done every 6
months for 2 years, then annually thereafter. The blood tests and mammograms will be done
annually.
How Long Will I Be in the Study?
We think you will receive study treatment for 3 to 6 months, depending on which treatment
group you are assigned to. After the treatment has been completed your doctor will follow your
medical condition for up to 15 years to learn about the long-term effects of the study.
Your doctor will discontinue the study treatment if: the breast cancer returns in the breast
or an area outside the breast; you experience intolerable side effects; you and your doctor
decide that it is in your best interest to stop; or if new information become available which
suggests that the study treatment is unsafe or not effective for you.
9/15/01
Page 4 of 11
Participant Initials _____
IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
You can 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 Are the Risks of the Study?
While on the study, you will be at risk for these side effects. You should discuss these
with your doctor and the study staff. There may also be other side effects that we cannot
predict or are unforeseen or unexpected. Other drugs will be given to make the side effects less
serious and uncomfortable. Many side effects go away shortly after the study drugs are
stopped, but in some cases side effects can be serious, long lasting or permanent.
Cyclophosphamide + Methotrexate + 5-Fluorouracil (CMF)
Likely
• Temporary lowering of the number of white blood cells (cells that help your body fight
infection)
• Nausea, vomiting or diarrhea
• Abdominal discomfort
• Loss of appetite
• Loss of scalp and body hair
• Skin and nail discoloration
• Sores in the mouth and/or throat
• Irritation of the bladder (where urine is stored)
• Skin rash
• Hand and foot syndrome (the palms of the hands or soles of the feet tingle, become
numb, painful, swollen or red)
• Increased sensitivity to sunlight
Less Likely, But Serious
• Temporary lowering of the number of red blood cells (may cause a feeling of tiredness,
and shortness of breath)
• Temporary lowering of the number of blood platelet cells (cells that help your blood
clot)
• Blood in the urine
• Irregular heart beat (may occur right after the drugs are given)
• Weakened kidney function
• Eye irritation
• Nasal congestion
Doxorubicin + Cyclophosphamide (AC)
Likely
• Temporary lowering of the number of white blood cells (cells that help your body fight
infection)
• Temporary lowering of the number of red blood cells (may cause a feeling of tiredness
and shortness of breath)
9/15/01
Page 5 of 11
Participant Initials _____
IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
• Temporary lowering of the number of blood platelet cells (cells that help your blood
clot)
• Nausea, vomiting or diarrhea
• Loss of scalp and body hair
• Skin and nail discoloration
• Sores in the mouth and/or throat
• Urine may turn red for 1-2 days (due to the color of the doxorubicin)
• Irritation of the bladder (where urine is stored)
• Sensitivity to sunlight
Less Likely, But Serious
• Blood in the urine
• Heart damage
• Irregular heart beat (may occur right after the drugs are given)
• Congestive heart failure (a decrease in the heart’s ability to pump effectively, which may
lead to shortness of breath)
• Skin tissue damage if some of the drug leaks from the vein while it is being given
• Acute leukemia
Capecitabine
10/03
Likely
• Diarrhea
• Nausea and vomiting
• Sores in the mouth and/or throat
• Abdominal pain
• Constipation
• Hand and foot syndrome (the palms of the hands or soles of the feet tingle, become
numb, painful, swollen or red)
Less Likely, But Serious
• Temporary lowering of the number of white blood cells (cells that help
your body fight infection)
• Temporary lowering of the number of red blood cells (may cause a feeling
of tiredness and shortness of breath)
• Temporary lowering of the number of blood platelet cells (cells that help
your blood clot)
• Dizziness
• Headache
• Insomnia (difficulty sleeping)
• Loss or decrease of appetite
• Eye irritation
• Muscle aches
• Edema (fluid retention, which can cause swelling of the body)
• Problems with liver function (as seen on a blood test)
9/15/01
Page 6 of 11
Participant Initials _____
IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
10/03
In some individuals, the side effects associated with chemotherapy may be severe or lifethreatening. You will be asked to contact your doctor immediately if you have:
 Diarrhea: if you have more than 3 bowel movements in one day or diarrhea at night
 Mouth sores: if you have pain, redness, swelling or sores in your mouth
 Pain or swelling of the hands or feet: if you have pain, swelling or redness of your hands
or feet that prevents normal activity
 Fever or infection: if you have a temperature of 100.0oF or higher, or other signs of
infection
10/15/01
There are many medications (prescription and non-prescription), which may interact with
capecitabine. Your doctor will review all of the medications you are currently taking before
your participation on this treatment study. You should not take any new medications without
discussing it with your doctor first. If you are taking blood thinners such as warfarin
(Coumadin®) or phenytoin (Dilantin®), your doctor will need to monitor these medications
while your are taking capecitabine.
10/03
Reproductive Risks (Pregnancy/Birth Control): Due to the unknown risks and potential
harm to the unborn fetus, sexually active women of childbearing potential 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 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. We encourage you to discuss this issue further with
your doctors if you have any questions. A woman should not nurse her baby while on this
study. Ask about counseling and more information about preventing pregnancy. Pregnant
women and nursing mothers are excluded from participation in this study. If a woman
becomes pregnant, she will be withdrawn from the study. Since most methods of birth control
are not 100% reliable, if you are a sexually active woman of childbearing potential, a
pregnancy test (at least 10 days from your last normal menstrual period) is required.
For more information about risks and side effects, ask your doctor or contact your researcher.
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 benefit to
you. We hope the information learned from this study will benefit other patients with
breast cancer in the future.
The possible benefits of taking part in the study may be the same as receiving standard
CMF or AC treatment without being in the study. Although capecitabine is known to be
effective in women with metastatic breast cancer, this study will help the researchers
learn if capecitabine is as effective as standard adjuvant chemotherapy in older women
with early stage breast cancer.
9/15/01
Page 7 of 11
Participant Initials _____
IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
What Other Options Are Available?
You do not have to participate in this study to receive treatment for your breast cancer.
Standard treatment for your type of breast cancer can include surgery, chemotherapy,
radiation therapy, and tamoxifen. You do not have to participate in this study to receive
adjuvant CMF or AC chemotherapy.
Please talk to your doctor about these and other options.
What About Confidentiality?
Efforts will be made to keep your personal information confidential. We cannot guarantee
absolute confidentiality. Your personal information may be disclosed if required by law.
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 and
data analysis include groups such as:
Southeast Cancer Control Consortium (SCCC) Operations Office
Cancer and Leukemia Group B (CALGB)
National Cancer Institute (NCI)
Food and Drug Administration (FDA)
Office for Human Research Protections (OHRP)
Institutional Review Board (IRB) at your hospital
A qualified representative of Roche Laboratories, Inc., the drug manufacturer of
capecitabine
Possible other federal or state government agencies
Y-ME, a patient support organization, will be provided with your name solely for the
purpose of evaluating an educational program related to this study.
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.
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.
What Are The Costs?
Taking part in this study may lead to added costs to you or your insurance company. You or
your insurance carrier will be responsible for the costs of clinic visits, any hospital admissions,
laboratory tests, x-rays, scans, chemotherapy treatments, and any other tests. Please ask your
doctor about any added costs or insurance problems. You will not be paid to participate in this
study.
9/15/01
Page 8 of 11
Participant Initials _____
IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
In the case of injury or illness resulting from this study, emergency medical treatment is
available but will be provided at the usual charge. No funds or monies have been set aside to
compensate you in the event of injury.
You or your insurance company will be charged for continuing medical care and/or
hospitalization.
The study drug capecitabine (Xeloda) will be provided free of charge to your doctor by Roche
Laboratories, Inc., through the Division of Cancer Treatment and Diagnosis of the National
Cancer Institute (NCI). However, if the manufacturer of this drug should discontinue to supply
it for this study, you may be required to purchase subsequent doses. You and/or your insurance
company will be responsible for all other costs of the study treatment.
What Are My Rights As A Participant?
Taking part in this study is voluntary. You may choose not to take part or you may leave the
study at any time. Leaving the study will not result in any penalty or loss of benefits to which
you are entitled. If you withdraw from the study, you will continue to be followed and clinical
data will be collected from your medical records as long as we have your consent. You are free
to seek care from a doctor of your choice at any time.
A Data and Safety Monitoring Board, an independent group of experts, will be reviewing
the data from this research throughout the study. We will tell you about the new information
from this or other studies that may affect your health, welfare or willingness to stay in this
study.
Who Do I Call If I Have Questions Or Problems?
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 ____________________).
Related studies
The researchers are also interested in learning more about breast cancer in older women,
such as the possibility of predicting response to cancer treatment, survival after treatment,
and to learn if there are differences between older and younger women. These research
studies will measure levels of certain enzymes and proteins called “tumor markers”, which
are found in cancer tissue. These research studies will not involve the study of cancer
genes that can be inherited (passed from parents to children).
The results of these research studies will not be given to you or your doctor, nor will the
results have any effect on your treatment.
9/15/01
Page 9 of 11
Participant Initials _____
IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
If you agree a sample of your breast cancer tissue, which was taken at the time of
diagnosis for routine testing, will be sent to a CALGB research laboratory where it will be
used for these studies.
It is not possible for you or the CALGB to know what studies of breast cancer may be
appropriate in the future. So we ask that you give permission in advance for other studies
related to breast cancer without being re-contacted for each test. The research that may
be done with your breast cancer tissue samples probably will not help you. It might help
people in the future who have breast cancer.
In addition, some of this tissue may be used to establish products that could be patented
and licensed. There are no plans to provide financial compensation to you should this
occur.
There will be no charge to you for participating in these research studies. If you decide now to
allow your tissue sample to be used in these and future studies and then change your mind at
any time about participating in the studies, just contact your institution and let them know that
you do not want the researchers to use your sample. Then it will no longer be used for research.
The results from these studies may be published, but individual patients will not be identified
in these publications.
Your participation in these research studies is entirely voluntary. You do not have to participate
in this portion of the study to receive the study treatment.
I agree to the use of my specimen for research and teaching purposes related to my cancer,
including the specific studies described above.
_____ Yes _____ No
Initials _____
I agree to be contacted in the future to discuss whether I will give permission for my specimen
to be used for genetic research.
_____ Yes _____ No
Initials _____
I agree to allow my specimen to be used for research unrelated to my cancer.
_____ Yes _____ No
9/15/01
Initials _____
Page 10 of 11
Participant Initials ____
IRB Approval Date ____________
Version: Update #14 5/15/06
CALGB 49907
Southeast Cancer Control Consortium Consent Form
4/02
Where Can I Get More Information?
You may call the NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237)
or TTY: 1-800-332-8615 or you may visit the Cancer Information Service Website:
http://www.cancer.gov/cis
You may visit the NCI’s Web site:
http://www.cancer.gov
This website contains comprehensive clinical trials information and accurate cancer
information.
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.
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.
10/15/04
My signature below means that I have voluntarily agreed to participate in this research study. I
will be given a copy of all 11 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)
9/15/01
_________________________________
(Signature of Person Obtaining Consent)
Page 11 of 11
CALGB 49907
Southeast Cancer Control Consortium Withdrawal of Treatment Consent
I, _____________________________, withdraw my consent for treatment on CALGB 49907.
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 __________________________ CALGB ID Number _____________
(Please Print Name)
Participant Signature _________________________________
Date _______________
Witness Signature ___________________________________
Date _______________
9/15/01
CALGB 49907
Southeast Cancer Control Consortium Withdrawal of Consent
I, __________________________, withdraw my consent to participate in CALGB 49907 and
refuse to be followed and have clinical data collected from my medical records.
Participant Name __________________________ CALGB ID Number _______________
(Please Print Name)
Participant Signature _________________________________
Date _______________
Witness Signature ___________________________________
Date _______________
9/15/01
CALGB 49907
Southeast Cancer Control Consortium Consent Form
CALGB 49907 Y-ME TELEPHONE CONTACT PROGRAM
Because you have said that you are undecided about whether or not your want to participate in
this clinical trial (research study) that your doctor and/or the medical staff have already discussed
with you, we would like to offer you the opportunity to speak with a Y-ME volunteer.
Sometimes women who are making decisions about their cancer treatment find it helpful to
speak with someone who has previously received treatment for cancer. The Y-ME National
Breast Cancer Organization has a special program to provide telephone contact from a breast
cancer survivor. Through this program women in your age group from the Y-ME organization
who have received chemotherapy for breast cancer are available to provide information about the
clinical trial and to discuss their experiences during breast cancer treatment.
If you agree to be contacted, your doctor will forward your name and telephone number to the
Y-ME National Breast Cancer Organization. A few days later, a breast cancer counselor from
Y-ME will contact you over the phone. During the telephone call, the Y-ME counselor will
provide general information about the clinical trial, the informed consent document, the
counselor’s personal experience with participation in a clinical trial, and emotional support. If
you wish, the Y-ME counselor can speak with a member of your family, or provide a follow-up
call at another date.
Efforts will be made to keep your personal information confidential. We cannot guarantee
absolute confidentiality. Your personal information may be disclosed if required by law.
Your participation in this telephone contact program is voluntary. Refusal will not affect your
medical care in any way.
By signing below, you indicate that you have read this form and willingly consent to be called.
You will receive a copy of this form with the informed consent document for this clinical trial
attached. We encourage you to have this document with you at the time of the telephone call.
AUTHORIZATION
I have read this form and have decided that I will participate in the telephone contact program
described above.
______________________________________
(Please Print Participant Name)
______________________________________
(Participant Signature)
4/15/02
123
________________________
(Date)