A Phase I Trial of BAY 43-9006 for Patients with Recurrent or Progressive Malignant Glioma
Protocol Version: April 12, 2005
| Purpose of Study | Eligibility Criteria | Treatment Schedule | Sample Informed Consent | Patient Information |
Inclusion Criteria
Patients
must be at least 18 years of age.
Patients
must have histologically proven malignant glioma (anaplastic astrocytoma,
anaplastic oliogodendroglioma or glioblastoma multiforme) which is
progressive or recurrent after radiation therapy ± chemotherapy. Patients with previous low grade glioma who progressed after
radiotherapy ± chemotherapy and are biopsied and found to have a high grade
glioma are eligible.
Patients
must have measurable progressive or recurrent malignant glioma by
MRI or CT imaging. (Within 14 days before starting treatment).
Patients
must have recovered from toxicity of prior therapy. An interval of at least
3 months must have elapsed since the completion of the most recent course of
radiation therapy, while at least 3 weeks must have elapsed since the
completion of a non-nitrosourea containing chemotherapy regimen, and at
least 6 weeks since the completion of a nitrosourea containing chemotherapy
regimen.
Patients
must have a Karnofsky performance status ³
60% (i.e. the patient must be able to care for himself/herself with
occasional help from others).
Patients
must have normal hematologic, renal and liver function. Patients
must meet the following laboratory criteria: Absolute Neutrophil Count ³1500/mm3;
Platelets ³
100,000/mm3; Creatinine £
1.7mg/dl; Total Bilirubin £
1.5mg/dl; Transaminases £
4 times above the upper limits of the institutional norm; PT, PTT, INR
within institutional norm.
Patients must be able to provide written informed consent.
Patients with the potential for pregnancy or impregnating their partner must agree to follow acceptable birth control methods to avoid conception. Women of childbearing potential must have a negative serum pregnancy test. (The anti-proliferative activity of this experimental drug may be harmful to the developing fetus or nursing infant.)
Exclusion Criteria
Patients
with serious concurrent infection or medical illness which would jeopardize
the ability of the patient to receive the treatment outlined in this
protocol with reasonable safety. (Examples
of medical illnesses are [but not limited to] the following: uncontrolled hypertension, symptomatic congestive heart failure,
unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
situation that would limit compliance with study requirements.)
Patients
who are pregnant or breast-feeding. (The anti-proliferative activity of this
experimental drug may be harmful to the developing fetus or nursing infant.)
Patients
who have received more than two prior treatment.
Patients
receiving concurrent therapy for their tumor (with the exception of
steroids).
Patients
with a concurrent malignancy are ineligible unless they are patients with
curatively treated carcinoma-in-situ or basal cell carcinoma of the skin.
Patients with a prior malignancy are ineligible unless they have been
free of disease for ³
five years.
Patients
must not have any evidence of bleeding diathesis.
BAY 43-9006 will
be administered orally BID for 4 consecutive weeks.
The 28
day period will represent one treatment cycle. The starting dose for this phase
I study is 200mg BID. Only
one dose of BAY 43-9006 will be taken on the first day of the first cycle of
therapy to facilitate definition of the plasma concentration-time profile. BID dosing will begin on day 2 of the first cycle.
Treatment of an individual patient will continue
until there is objective or clinical evidence of either disease progression or
treatment-related, dose-limiting toxicity, or if the patient decides to
discontinue treatment for any reason. All
patients will be given drug to take home and a drug calendar that explicitly
details how many tablets the patient will be taking each day. The patient will be asked to record the amount of drug
actually taken as well as the date and time of each dose.
Phase I Trial of BAY 43-9006 for Patients with Recurrent or Progressive Malignant Gliomas
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 family and friends.
You are being asked to take part in this study because you have a brain tumor (glioma), which has grown or has recurred.
WHY IS THIS STUDY BEING DONE?
The purpose of this study is to find the highest dose of an investigational agent called BAY 43-9006 that can be given without causing severe side effects. This research is being done because currently, there are few effective treatments for this type of cancer. This drug may be active in other types of cancer and we are studying the proper dose of BAY 43-9006 to give to patients with brain tumors. This means we will give increasing doses of BAY 43-9006 until patients have major side effects. You will be assigned a dose when you enter the study. You will be told what your dose is and it will not be increased. You will be given the same or lower dose throughout your treatment. We will also be looking at the side effects of BAY 43-9006.
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY?
About 6-36 people will take part in the study.
WHAT IS INVOLVED IN THE STUDY?
If you take part in this study you will have the following tests and procedures:
Before treatment starts, you will have a complete physical exam, blood and urine tests. A chest x-ray and ECG (heart tracing) will be done. An MRI or CT scan of the brain will also be performed. Women able to have children will have a pregnancy test.
This drug is given by mouth twice every day for four weeks. Each 4 week (28 day) period is called a treatment cycle. One the first day you start BAY 43-9006 you will only take one dose. Beginning on day two you will take BAY 43-9006 twice a day. You will be asked to record the amount of drug taken each day in a drug diary. A brain scan will be performed before starting treatment with BAY 43-9006 and after the second cycle of drug. Brain scans will be repeated every 8 weeks (2 cycles). The brain scans (MRI or CT) would be part of routine cancer care.
During the study, a physical exam and neurologic exam will be repeated. Routine blood tests will be done before each cycle of BAY 43-9006. If at any point your blood counts are low, these blood tests will be repeated more often.
As part of this study, we will also be collecting extra blood samples in order to check the amount of BAY 43-9006 in your blood. On Day 1 of the study you will take your first dose of BAY 43-9006 in the clinic. We will collect 10 extra blood samples. This will require you to stay in the clinic for at least 8 hours. On the 2nd day we will collect one blood sample. During the 2nd week of your treatment we will collect 10 samples and the 6th week of your treatment we will collect 10 more samples. On the days blood samples are being collected you may not take BAY 43-9006 until you arrive at the clinic and the first blood sample is drawn. On the days that 10 blood samples are being collected you will be asked to stay in the clinic for at least 8 hours. Approximately 2 tablespoons of blood are drawn for each sample. The total amount of blood drawn on each of these days is approximately 10 ounces (or 300 mL). These extra blood tests are for research purposes only and would not be part of your standard care. The costs associated with collecting and processing these blood samples will not be charged to you or your insurance company.
HOW LONG WILL I BE IN THE STUDY?
BAY 43-9006 will be continued on the same schedule unless your tumor grows, or you have side effects that warrant discontinuation, or you desire to stop treatment. The researcher may decide to take you off this study if your doctor thinks it will be in your best interest, your condition worsens, or new information becomes available.
Your participation in your clinical trial is completely voluntary. You can stop participating at any time. If you decide not to participate, or wish to withdraw your consent to participate in this treatment at any time, it will in no way affect your regular treatments or medical care. If you stop participating in this study you may be asked to return to the clinic for a final evaluation. However, if you decide to stop participating in the study, we encourage you to talk to the researcher and visit your regular doctor first.
WHAT ARE THE RISKS OF THE STUDY?
While on the study, you are at risk for these side effects. You should discuss these with the researcher and/or your regular doctor. There also may be other side effects that we cannot predict. Other drugs will be given to make the side effects less serious and uncomfortable.
Many side effects go away shortly after the BAY 43-9006 is stopped, but in some cases side effects can be serious or long-lasting or permanent or fatal.
Expected Side effects include:
· High blood pressure
· Fatigue
· Diarrhea
· Hand-foot syndrome (redness, peeling and sometimes pain of the soles of the feet and palms of the hands) and peeling rash
Other side effects:
Flu-like symptoms, fever, chills, joint pain, arthritis, muscle pain,
Allergic reactions, dry skin, hair loss, changes in nail appearance, vitiligo (skin disorder resulting in pigmentation (color) changes), itching
· Abdominal pain/cramping, swelling of the abdomen, constipation, nausea, vomiting, excess gas, indigestion/heartburn, abnormal liver functions
· Low blood counts which could lead to infection
· Bleeding in the stomach, intestines or rectum, bleeding in the kidneys or bladder
· Pancreatitis (inflammation in your pancreas). The pancreas is a large gland behind your stomach which secretes digestive enzymes and hormones. Elevated amylase/lipase (enzymes produced by the pancreas).
· Numbness or tingling sensations
· Loss of appetite, weight loss
· Kidney failure, increase of sugar in the blood (hyperglycemia)
· Shortness of breath, low oxygen in the blood, pneumonia, collapsed lung, fluid around the lungs
· Dehydration, difficulty swallowing, mouth sores and inflammation of the mouth
· Brain stem stroke (rupture or obstruction of an artery of the brain stem)
· Increase PT/PTT (tests that measure the clotting ability of the blood)
There is the possibility that BAY 43-9006 will interact with other medications you are taking. This is particularly important if you are taking medication to control or prevent seizures. If you are taking one of these mediations (warfarin, quinidine, cyclosporine, digoxin, Phenobarbital, Dilantin/phenytoin, Depakote/valproic acid), your physician will monitor you carefully for side effects and check your drug levels carefully.
Side effects due to blood drawing may include: pain, bruising, bleeding or other discomfort at the blood drawing site. Anemia (low red blood cells), fainting or infection at the blood drawing site may occur (very unlikely).
Reproductive risks: Because there may be a risk of birth defects if a fetus is exposed to BAY 43-9006, you should not use this drug if you and your partner are planning to have a baby during this study or two months following the end of the study. A barrier method of birth control (i.e. condom) must be used during the study and for eight (8) weeks after your last dose of study drug. You should not nurse a baby while on this study. Ask about counseling and more information about preventing pregnancy.
Financial risks: There may be extra costs with this treatment. Some of the costs may not be covered by the hospital or the insurance company. We encourage you to work closely with your insurance company to find out exactly what is covered for this research study.
For more information about risks and side effects, ask the researcher or contact .
ARE THERE BENEFITS TO 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 brain tumors in the future.
WHAT OTHER OPTIONS ARE THERE?
Should your disease become worse, or if you have severe side effects, this therapy may be discontinued and other means of treating you will be discussed. You may choose at this time, or any time in the future to have no further therapy; other than care for relief of your symptoms (supportive care). You may also consider other treatments for your disease such as further surgery, radiation therapy or chemotherapy. Other research options may also be available to you.
Please talk to you doctor about these and other options.
WHAT ABOUT CONFIDENTIALITY?
This section tells you what information about you may be used and given out in this study and who may give and receive the information. By signing this consent form, you agree that health information that identifies you may be used and/or given out as needed in this study. _________________ has a policy to protect health information that may identify you. Federal and state laws also protect your privacy. ______________________ has procedures in place to support these policies and laws.
a. What information about you may be used or given out in this study?
Information that identifies you and relates to your health or medical condition may be used or given out in this study. Information that identifies you can include your name, address, telephone number, date of birth, Social Security number and other details about you. Information that relates to your health or medical condition includes:
Information obtained from the activities and procedures outlined in this consent form, which may include:
i) things done to see if you can join this study, such as physical examinations, blood and urine tests and any other information that you share with us, including information about your health history and your family health history; and
ii) information obtained during the study, such as how you respond to the study activities or procedures, information we learn in study visits, phone calls, surveys, physical examinations, blood and urine tests, x-rays and other tests and any other medical information we learn from you as a participant in this study.
b. Who may use and give out information about you?
Some people may see your health information and may give out your health information during this study. These include the researcher and the research staff, the institutional review boards and their staff, legal counsel, audit and compliance staff, officers of the organization and other people who need to see the information to help this study or make sure it is being done as it should.
c. Who may see your health information?
Other organizations may see your health information during this study. These include:
· Governmental entities that have the right to see or review your health information, such as the Office of Human Research Protections and the Food and Drug Administration
· Doctors and staff at other places that are participating in this study
· The pharmaceutical sponsor, Bayer Pharmaceuticals Corporation.
· The sponsor of this study and people that the sponsor my contract with for this study. The name of the sponsor is CTEP/NCI.
· The Contract Research Organization.
· The Data Safety Monitoring Board
· An outside institutional review board
· NABTT CNS Consortium
d. Why will this information be used and given out?
Your information will be used and given out to carry out this study and to evaluate the results of this study.
e. What if you decide not to give your permission to use and give out your health information?
You do not have to give your permission to use or give out your health information. However, if you do not give permission, you may not participate in this study.
f. May you withdraw or cancel your permission?
You may cancel your agreement to allow your health information to be used or given out at any time by sending a written notice to the Institutional Review Board Office, __________________________________. If you do this, you are leaving this study. If you leave this study, no new health information about you will be gathered after that date. However, information gathered before that date may be used or given out if it is needed for this study or any follow-up for this study.
g. Is your health information protected after it has been given to others?
If your health information is given to someone not covered by these policies and laws, that information may no longer be protected, and may be used or given out without your permission.
h. Does this consent form have an end date?
This authorization to use and give out health information continues until the end of this study and any necessary data analysis follow-up activities for this study.
A) What is the role of the IRB?
Research studies involving human volunteers are reviewed by an Institutional Review Board (IRB). The IRB is made up of doctors, nurses, scientists, non-scientists and people from the community. The IRB is responsible for protecting participant’s rights.
WHAT ARE THE COSTS?
Taking part in this study may lead to added costs to you or your insurance company. Some of the costs of the blood tests and brain scans may not be covered by your insurance company. We encourage you to work closely with your insurance company to find out exactly what is covered for this research study.
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 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.
NCI (National Cancer Institute) will provide you with the investigational agent free of charge for this study. Should this agent become commercially available or approved for this indication during the course of this study, you may be asked to purchase subsequent doses of the drug needed to complete the study in the event that the company no longer provides the drug.
You will receive no payment for taking part in this study.
WHAT ARE MY RIGHTS AS A PARTICIPANT?
Taking part in this study is voluntary. You may choose not to take part or 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.
We will talk to you about new information that may affect your health, welfare, or willingness to stay in this study.
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or a research-related injury, contact the researcher __________________ (NAME{S}) at __________________ (TELEPHONE NUMBER) .
For questions about your rights as a research participant, contact the__________________ (NAME OF CENTER) Institutional Review Board (which is a group of people who review the research to protect your rights) at __________________ (TELEPHONE NUMBER ).
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
Visit the NCI's Web sites
cancerTrials: comprehensive clinical trials information
http://cancertrials.nci.nih.gov.
CancerNet: accurate cancer information including PDQ
http://cancernet.nci.nih.gov.
You will get a copy of this form. You may also request a copy of the
protocol (full study plan).
SIGNATURE
I agree to take part in this study.
Participant ________________________________
Date _____________________
Investigator ________________________________
Date _____________________
Witness ___________________________________
Date ____________________