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UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
CONSENT TO PARTICIPATE IN A RESEARCH STUDY
Study Title: CALGB 30601: A Phase II Study of Dasatinib (NSC #732517) in Patients with Previously Treated Malignant Mesothelioma 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. You are being asked to take part in this study because you have already been treated for malignant mesothelioma and further surgery, radiation treatments, or regular chemotherapy are felt to offer little benefit. Dr. Sarita Dubey and associates of the Department of Medicine at the University of California, San Francisco are conducting a research study to compare the effects (both good and/or bad) the drug dasatinib has on you and your mesothelioma. Currently, there is only one approved chemotherapy treatment for mesothelioma (cisplatin and pemetrexed) in the United States. This study is being done in patients who have already had treatment with pemetrexed and in those whose cancer has recurred or progressed despite chemotherapy. Dasatinib has been shown to slow cancer growth in the laboratory and in animals by reducing the activity of one or more of the proteins that cause cancer cells to multiply and grow. Dasatinib is approved by the FDA for use in patients with chronic myeloid leukemia or acute lymphoblastic leukemia who have developed resistance or intolerance to imatinib (Gleevec), but is considered investigational for the treatment of mesothelioma. We will also be studying your blood and tumor specimens to determine if there is a way to predict how your tumor will respond to dasatinib. How many people will take part in the study? About 10 people will be enrolled in this study at UCSF. There will be about 42 people that will take part in this study at locations across the country. What will happen if I take part in this study? Before you begin the main part of the study…
You will need to have the following exams, tests or procedures to find out if you can be
in the main part of the study. These exams, tests or procedures are part of regular
cancer care and may be done even if you do not join the study. If you have had some of them recently, they may not need to be repeated. This will be up to your study doctor. • Blood tests (about 6 teaspoons of blood before you enter the study and then every 4 weeks while you are being treated with the dasatinib) • CT scan or MRI of chest and abdomen (before you enter the study and then every 8 weeks while you are being treated with the dasatinib) • EKG (electrocardiogram) – a recording of the electrical activity of the heart – will be • Pregnancy test, if you are a woman of child-bearing potential CT Scan: A CT scan is a type of x-ray that allows your doctors to see inside your chest, abdomen, and pelvis to observe the size of your tumor. For the CT scan, you may be given a “contrast material” (like a dye) to drink, an IV (intravenous) line may be started by a needle stick in the arm and a “contrast material” may be injected through the line, or you may receive a rectal contrast (less likely). The IV contrast material is a special dye used to get clearer pictures of your body cavity. The oral contrast material is used to help outline the stomach and intestines. The rectal contrast fills up the loops of your lower bowel so the doctors can better visualize your tumor. You will lie flat on a table that will move you into the CT scan machine. You will be asked not to move and may be asked to hold your breath for a few seconds. The CT scan is done in the radiology department and takes about 30 minutes. The CT scan is considered a part of your standard medical care. MRI Scan: An MRI (Magnetic Resonance Imaging) test takes an image of your body to observe the location and size of your tumor. For the MRI test, you may receive gadolinium (a contrast agent) through a vein in your arm. Gadolinium is an agent that causes some tumors to appear much brighter than normal tissue on MRI scans; before gadolinium is injected the tumor may not be visible. An intravenous catheter (a tiny tube inserted into a vein) may be placed in your arm for the purpose of injecting the contrast agent. You will then lie down on a narrow bed, which will then be placed in a tunnel that is 6 feet long by 22 inches wide and open at each end. You will lie there quietly for about one hour, during which time you will hear a loud machine-like noise. The MRI scan is done in the radiology department and takes approximately 1.5 hours. The MRI scan is considered a part of your standard medical care. Many of these tests will be repeated during the study. If you participate in this study, some of these tests may be done more frequently than if you were not taking part in this research study. There is a chance that there may be an interaction of dasatinib with a drug(s) you may be currently taking. Please let your doctor know what those might be. A list of drugs that are prohibited for use during dasatinib treatment is provided at the end of this consent form. Along with the drugs on the attached list, you are asked to refrain from taking aspirin, anti-coagulants (e.g. ibuprofen), and any anti-platelet agents (e.g. Plavix) during or for 7 days before the beginning of dasatinib therapy. Also if you receive bisphosphonate therapy (e.g. Zometa) this should be withheld for the first 8 weeks of study treatment. Treatment
During the main part of the study…
If the exams, tests and procedures show that you can be in the main part of the study, and you choose to take part, then you will receive the following treatment. You will take one dasatinib tablet by mouth twice daily every day until your doctor tells you to stop. The tablets should be taken about the same time each day approximately 12 hours apart (i.e., 8 a.m. and 8 p.m.) with about 1 cup of water. Take the dasatinib whole, do not cut or crush the tablets. It does not matter whether or not you take the tablets with food. You will be given a calendar to help remind you to take the dasatinib; please fill out the calendar each time you take the medicine. If you forget to take a dose, take it as soon as you remember, however, if the dose is missed by more than 6 hours, the dose should be skipped. Do not take 2 doses at one time. Record the dose as missed on the calendar. Call your study nurse if you have any questions about a missed dose. Dasatinib is eliminated from your body through the liver. The use of certain other medicines may change the levels of dasatinib in your bloodstream. Such changes can increase the side effects, or reduce the activity of the medicines you are taking, including dasatinib. Your study doctor will review all medicines you take including prescription and over-the-counter medicines, vitamins, antacids, and herbal supplements. Dasatinib is best absorbed from your stomach into your bloodstream in the presence of stomach acid. You should avoid taking medicines that reduce stomach acid such as TAGAMET® (cimetidine), PEPCID® (famotidine), ZANTAC® (ranitidine), Protonix (pantoprazole), Prilosec (omeprazole), and Aciphex (rabeprazole) . Medicines that neutralize stomach acid, such as MAALOX® (aluminum hydroxide/magnesium hydroxide), TUMS® (calcium carbonate), or ROLAIDS® (calcium carbonate and magnesia) may be taken up to 2 hours before or 2 hours after dasatinib. You also should not drink grapefruit juice while on this study. You will return to the clinic every 4 weeks for a physical examination and routine blood tests. You will be asked to bring the completed medication calendar and the study medication containers with all unused medication to these visits. Also, please tell your doctor about any other medicines you are taking. In order to be treated on this study, tumor tissue that was obtained from you before treatment with dasatinib must be available. Analysis of this tissue will be done at a CALGB laboratory to determine whether certain tumors have characteristics that make them more likely to respond to drugs like dasatinib. The results of these research studies will not be provided to you or your physicians. You will continue taking the dasatinib until your doctor decides the treatment is no longer working. While on treatment, you will be asked to return to the clinic every 4 weeks for study examinations which will take place in the clinic and take about 90 minutes to complete. After you stop taking the dasatinib you will be asked to come in for follow-up evaluations including a physical exam, updated medical history, evaluation of any treatment-related side effects, and a CT scan/MRI at least every 2 months for 1 year, then every 4 months for 1 year, and then every 6 months for 1 year (for a total of 3 years). Each follow up visit will take place in the clinic and take about 90 minutes to complete. Your doctor may decide to take you off this study if: • The treatment does not work in your cancer. • Your health gets worse. • Your cancer begins to grow.
Can I stop being in the study?
Yes. You can decide to stop at any time. Tell the study doctor if you are thinking about
stopping or decide to stop. He or she will tell you how to stop your participation safely.
It is important to tell the study doctor if you are thinking about stopping so any risks from
the dasatinib can be evaluated by your doctor. Another reason to tell your doctor that
you are thinking about stopping is to discuss what follow-up care and testing could be
most helpful for you.
The study doctor may stop you from taking part in this study at any time if he/she
believes it is in your best interest, if you do not follow the study rules, or if the study is
stopped.
What side effects or risks can I expect from being in the study? While on the study, you are at risk for these side effects. You should discuss these with the researcher and/or your doctor. Everyone taking part in the study will be watched carefully for any side effects. There also may be other side effects that we cannot predict. Other drugs will be given to make side effects less serious and uncomfortable whenever possible. Many side effects go away shortly after the dasatinib is stopped, but in some cases side effects can be serious, long lasting or may never go away. • Lowered white blood cell count (which may lead to fever and infection) • Lowered red blood cell count (anemia may cause tiredness, or shortness of • Lowered platelet count (which may lead to bruising or bleeding) • Diarrhea • Fatigue • Rash / flaking or shedding of outer layer of skin • Nausea • Headache or head pain • Pleural effusion, which is a collection of fluid in the chest (may cause difficulty in breathing, chest pain, fever or a nonproductive cough) Less Likely
• vomiting • Decrease in blood calcium and/or phosphate levels • Increase in liver enzymes • Pain in the belly, chest, joints, muscles or general pain • Cough • Nerve damage causing numbness, tingling and/or burning • Chills • Weight gain or loss • Constipation • Ulcer, irritation or sores, with possible bleeding in the digestive tract • Dizziness • Pericardial effusion, which is a collection of fluid around the heart (may cause chest pain, light-headedness, abnormal heart beat, etc.) • Loss of appetite • Fever • itching • infection • feeling of fullness and tightness in the belly Rare but Serious
• Changes and irregularities in heart rhythm • Tumor lysis syndrome (Sudden and rapid breakdown of tumor cells that can lead to damage of kidneys and changes in blood chemistry leading to damage to internal organs and even potentially death) The doctor will check blood tests four changes that may indicate the occurrence of this condition. • Bleeding into the brain or spinal cord • A syndrome caused by high blood pressure that may cause symptoms like headache, confusion, seizures, and vision loss Blood drawing (venipuncture) risks: Drawing blood may cause temporary
discomfort from the needle stick, bleeding, bruising, and infection.
Radiation (x-ray) risks: the amount of radiation you will be exposed to is relatively
small. Such doses of radiation may be potentially harmful, but the risks are so small
that they are difficult to measure. If you have already had many x-rays, you should
discuss this with the researchers before agreeing to be in the study.
CT scan risks: CT scans involve the risks of radiation (see above). In addition, if
contrast material (iodine dye) is used, there is a slight risk of developing an allergic
reaction, from mild (itching, rash) to sever (difficulty breathing, shock, or rarely, death).
The contrast material may also cause kidney problems, especially if you are dehydrated
or have poor kidney function. The study doctors will ask you about any allergies or
related conditions before the procedure. If you have any of these problems, you may
not be allowed to have a CT scan.
Having a CT scan may mean some added discomfort for you. In particular, you may be
bothered by feelings of claustrophobia when placed inside the CT scanner, or by lying in
one position for a long time. If contrast material is used, you may feel discomfort when
it is injected. You may feel warm and flushed and get a metallic taste in your mouth.
Rarely, the contrast material may cause nausea, vomiting or headache.
MRI risks: Because the MRI machine acts like a large magnet, it could move iron-
containing objects in the MRI room during your examination, which in the process could
possibly harm you. Precautions have been taken to prevent such an event from
happening; loose metal objects, like pocket knives or key chains, are not allowed in the
MRI room. If you have a piece of metal in your body, such as a fragment in your eye,
aneurysm clips, ear implants, spinal nerve stimulators, or a pacemaker, you will not be
allowed into the MRI room and cannot have an MRI.
Having an MRI may mean some added discomfort for you. In particular, you may be
bothered by feelings of claustrophobia and by the loud banging noise during the study.
Temporary hearing loss has been reported from this loud noise. This is why you will be
asked to wear ear plugs. At times during the test, you may be asked to not swallow for
a while, which can be uncomfortable.
Because the risks to a fetus from MRI are unknown, pregnant women cannot participate
in this study.
Contrast agent (gadolinium) risks: If you have an MRI scan, you may receive the
contrast agent, gadolinium, through a vein in your arm. A few side effects of gadolinium
injection such as mild headache, nausea, and local pain may occur. Rarely (less than
1% of the time) low blood pressure and lightheadedness occurs. This can be treated
immediately with intravenous fluids. Very rarely (less than one in one thousand),
patients are allergic to gadolinium. These effects are most commonly hives and itchy
eyes, but more severe reactions have been seen which result in shortness of breath.
Patients with severe kidney disease sometimes have a bad reaction to gadolinium
contrast. The condition is called nephrogenic sclerosing fibrosis (NSF). It can cause
the skin to tighten or scar and can damage internal organs. Sometimes it can be life-
threatening. There are no reports of NSF in patients with normal kidney function.
Before you have a MRI scan requiring an injection of gadolinium contrast, you will have
a blood test in order to check the function of your kidneys. Based on your medical
history and results of the test, a doctor will decide whether it is safe for you to undergo
the MRI scan.
Reproductive risks: Because dasatinib can affect an unborn baby, you should not
become pregnant or father a baby while on this study. For this reason, both men and
women will be asked to practice an effective method of birth control while participating
in this study. You should continue with your birth control methods for at least 14 days
after receiving your final dose of dasatinib. Also, because the risk is unknown to young
children, you should not nurse your baby while on this study. Ask about counseling and
more information about preventing pregnancy.
Unknown risks: The drug being used in this study may have side effects that no one
knows about yet. The researchers will let you know if they learn anything that might
make you change your mind about participating in the study.
For more information about risks and side effects, ask the researcher or your study
doctor.
Are there benefits to taking part in the study? The benefit of dasatinib to patients with malignant mesothelioma is unknown. The purpose of this study is to find out if dasatinib can shrink or stop your tumor from growing. 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 mesothelioma 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: • Treatment with other commonly used chemotherapy drugs. • No therapy at this time with care to help you feel more comfortable. Please talk to your doctor about these and other options before deciding if you will take part in this study. Will my medical information be kept private? We will do our best to make sure that the personal information in your medical record is
kept private. However, we cannot guarantee total privacy. Your personal information
may be given out if required by law. If information from this study is published or
presented at scientific meetings, your name and other personal information will not be
used.

Organizations that may look at and/or copy your medical/research records for research,
quality assurance and data analysis include:
•
Bristol-Myers Squibb (the company that is providing the dasatinib to you free-of-charge) The CALGB has received a Certificate of Confidentiality from the federal government, which will help us to protect your privacy. The Certificate protects against the involuntary release of information about you collected during the course of the study. The researchers involved in this project may not be forced to identify you in any legal proceedings (criminal, civil, administrative, or legislative) at the federal, state, or local level. However, some information may be required by the Federal Food, Drug, and Cosmetic Act, the U.S. Department of Health and Human Services, or for purposes of program review or audit. Also, you may choose to voluntarily disclose the protected information under certain circumstances. For example, if you or your guardian requests the release of information about you in writing (through, for example, a written request to release medical records to an insurance company), the Certificate does not protect against that voluntary disclosure. What are the costs of taking part in this study? You and/or your health plan/insurance company 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 taking part in studies. Check with your health plan/insurance company to find out what they will pay for. Taking part in this study may or may not cost you or your insurance company more than the cost of getting regular cancer treatment. Bristol-Myers Squibb will provide you with the dasatinib free of charge for this study. Every effort will be made to ensure adequate supplies of the dasatinib are available, free of charge, for all participants. If the drug becomes commercially available for this indication there is a remote possibility that you may be asked to purchase subsequent
supplies. Your physician will discuss this with you should this situation arise.
Taking part in this study may lead to added costs to you or your insurance company.
Please ask about any expected added costs or insurance problems.

For more information on clinical trials and insurance coverage, you can visit the National
ical Trials and Insurance Coverage”
information from this Web site.
Another way to get the information is to call 1-800-4-CANCER (1-800-422-6237) and
ask them to send you a free copy.
Will I be paid for taking part in this study?
You will not be paid for taking part 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, Sarita Dubey, 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 415-353-7065.
Treatment and Compensation for Injury: If you are injured as a result of being in this
study, treatment will be available. The costs of the treatment may be covered by the
University of California depending on a number of factors. The University does not
normally provide any other form of compensation for injury. For further information
about this, you may call the office of the Committee on Human Research at 415-476-
1814.
What are my rights if I take part in this study?
Taking part in this study is your choice. You may choose either to take part or not to take part in the study . If you decide to take part in this study, you may leave the study at any time. No matter what decision you make, there will be no penalty to you and you will not lose any of your regular benefits. Leaving the study will not affect your medical care. You can still get your medical care from our institution. We will tell you about new information or changes in the study that may affect your health, welfare, or willingness to continue in this study. In case of injury resulting from this study, you do not lose any of your legal rights to seek payment by signing this form. Who can answer my questions about the study? You can talk to your study doctor about any questions or concerns you have about this
study. Contact your study doctor Sarita Dubey at 415-353-7065.
For questions about your rights while taking part in this study, call the office of the
Committee on Human Research, UCSF’s Institutional Review Board (a group of
people who review the research to protect your rights) at 415-476-1814.
It may be necessary to contact you at a future date regarding new information about the
treatment you have received. For this reason, we ask that you notify the institution
where you received treatment on this study of any changes in the address.
Please note: The following section of the informed consent form is about
additional research studies that are being done with people who are taking part in
the main study. You may take part in these additional studies if you want to. You
can still be part of the main study even if you say “no” to taking part in any of
these additional studies.

You can say “yes” or “no” to each of the following studies. Please mark your
choice for each study.
The results of these research studies will not be provided to you or your doctor, nor will
the results have any affect on your treatment. It is unlikely that what we learn from these
studies will have a direct benefit to you. However, the information learned from these
studies may benefit other patients in the future. The results of these studies may be
published, but individual patients will not be identified in these publications.
There will be no charge to you for participating in these research studies. Your samples
will only be used for research and will not be sold. The research done with your sample
may help to develop new products in the future.
You can stop participating in this part of the study at any time. If you decide now to
participate and then change your mind at any time about participating in these studies
for any reason, you should contact your study doctor (Dr. Sarita Dubey at 415-353-7065
or Thierry Jahan at 415-885-3792) and let them know that you do not want your
samples to be used for research. You can request that your remaining samples be
destroyed, and any remaining tissue will be destroyed and no longer used for research.
Please mark your choice by saying “yes” or “no” to each of the following:
Research Studies on Tissue and Blood

An additional objective of this clinical trial is for investigators to study your tissue and
blood to determine whether or not it has certain characteristics that may make you more
likely to respond to drugs like dasatinib. Tumor tissue that was obtained from you before
treatment with dasatinib will be used with your permission for this purpose. In addition, a sample of blood (about 2 teaspoons each time) will be collected before you receive treatment, after 1 month of treatment, and then after 2 months of treatment. Analysis of your tissue and blood specimens will be done at a CALGB approved laboratory. 1) I agree that my specimen(s) may be used for the research described above. _________ Yes
Research Studies on Biopsy Tissue

In addition to studying the tumor tissue that was previously obtained from you,
investigators are interested in studying your tumor after treatment has begun. If you
agree, a biopsy of your tumor will be taken for research purposes after you complete the
first course of treatment. Your study doctor may discuss this option with you. Agreeing
to the biopsy is not required for study participation. Analysis of this biopsy material will
be done at a CALGB approved laboratory.
2) I agree that a biopsy may be performed after the first cycle of treatment with dasatinib. _________ Yes
Storage of Your Specimens:
We would like to keep some of the tissue and blood that is left over for future research.
If you agree, these specimens will be kept indefinitely at the CALGB Pathology
Coordinating Office and may be used in research to learn more about cancer and other
diseases.
If you decide now that your specimens may be used for future research, you can
change your mind at any time. Just contact your study doctor, Dr. Sarita Dubey at 415-
353-7065 or Thierry Jahan at 415-885-3792 and let them know that you do not want
your specimens to be used for research. You can request that your remaining
specimens be destroyed, and any remaining tissue will be destroyed and no longer
used for research.
In the future, people who do research may need to know more about your health. While
CALGB may give them reports about your health, it will not give them your name,
address, phone number, or any other information that will let the researchers know who
you are. The CALGB Statistical Center will perform analyses of all data and store all
study results. Your specimens will not be stored with your name on it. Instead it will be
labeled with a special CALGB identification number. The only location where your
name and special identification number will be stored together is at the CALGB
Statistical Center. Your personal health information cannot be used for additional
research without additional approval from either you or a review committee.
Your specimens will be used only for research and will not be sold. The research done
with your specimens may help to develop new products in the future. You will not
receive any payment or financial benefit from any products, tests, or discoveries derived
from these specimens.
The research that may be done with your specimens is not designed specifically to help
you. It might help people who have cancer and other diseases in the future. Reports
about research done with your specimens will not be given to you or your doctor. These
reports will not be put in your health record. The research will not have an affect on your
care. The choice to let us keep left over specimens for future research is up to you.
You have the right to receive the planned therapy on this study without allowing your
specimens to be stored for future research. Please read the sentences below and think
about your choice. After reading the sentence, please mark your choice. No matter
what you decide to do, it will not affect your care.

3) My specimen(s) may be kept for future use in research to learn about, prevent, or treat 4) My specimen(s) may be kept for future use in research to learn about, prevent, or treat other health problems (for example: diabetes, Alzheimer disease, and heart disease). 5) My doctor or someone from CALGB may contact me in the future to ask me to take part You may call the National Cancer Institute’s Cancer Information Service at: 1–800–4–CANCER (1–800–422–6237) or TTY: 1–800–332–8615 You will get a copy of this form. You may also request a copy of the protocol (full study plan). If you want more information about this study, ask your study doctor. You have been given copies of this consent form and the Experimental Subject’s Bill of Rights to keep. You will be asked to sign a separate form authorizing access, use, creation, or disclosure of health information about you. PARTICIPATION IN RESEARCH IS VOLUNTARY. You have the right to decline to participate or to withdraw at any point in this study without penalty or loss of benefits to which you are otherwise entitled. If you wish to participate in this study, you should sign below. Drugs Prohibited During Dasatinib Treatment • ketoconazole (Extina, Nizoral) • miconazole (Monistat, Micatin) • voriconazole • ciprofloxacin (Cipro, Cipro XR) • clarithromycin (Biaxin XL, Biaxin XL Pac) • diclofenac (Cataflam, Voltaren) • doxycycline (Vibra-Tabs, Vibramycin) • enoxacin (Enroxil, Penetrex) • imatinib • quinidine (Quin-Release, Quinaglute Dura-Tabs, Quinidex Extentabs, Cardioquin, • carbamazepine (Carbatrol, Equetro, Tegretol, Tegretol XR) • nevirapine • pentobarbital (Nembutal, Nembutal Sodium) • phenobarbital (Phenobarbital, Solfoton) • phenytoin • quinidine (Quin-Release, Quinaglute Dura-Tabs, Quinidex Extentabs, Cardioquin, • procainamide (Procan SR, Procanbid, Pronestyl, Pronestyl-SR) • disopyramide (Norpace, Norpace CR) • amiodarone • erythromycins (E-Base, E-Mycin, ERYC, Ery-Tab, E.E.S. EryPed, Erythro, Erythrocin, Erythrocot, Ilotycin, Ilosone, My-E, PCE, Wintrocin) • clarithromycin (Biaxin XL, Biaxin XL Pac) • chlorpromazine • haloperidol (Haldol, Haldol Dec) • mesoridazine • methadone (Diskets, Dolophine, Methadose) • arsenic • pentamidine (Nebupent, Pentam 300) • sparfloxacin DRUGS TO AVOID TAKING DURING DASATINIB TREATMENT
• cimetidine (Tagamet ®) • famotidine (Pepcid ®) • ranitidine (Zantac ®) • pantoprazole

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