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The goal of this clinical research study is to learn the highest tolerable dose of irinotecan that can be given directly into the liver, in combination with other drugs given by vein.
This will be tested in patients with advanced solid tumors that have spread to the liver. The safety of these drug combinations will also be studied.
The Study Drugs :
Irinotecan is designed to stop cancer cells from making new DNA (the genetic material of cells). This may cause cancer cells to die.
Bevacizumab is designed to prevent or slow down the growth of cancer cells by blocking the growth of blood vessels that supply nutrients necessary for tumor growth.
Oxaliplatin is designed to block new cancer cells from growing.
Cetuximab is designed to prevent or slow down the growth of cancer cells by blocking proteins inside cancer cells.
Signing this consent form does not mean that you will be able to take part in this study. Before you can receive the drugs on this study, you will have "screening tests" to help the doctor decide if you are eligible to take part in the study. The following tests and procedures will be performed:
- Your medical and surgical history will be recorded.
- You will be asked about any drugs you may be taking.
- You will have a physical exam, including measurement of your height, weight, and vital signs (blood pressure, breathing rate, heart rate, and temperature).
- You will be asked how well you are able to perform the normal activities of daily living (performance status).
- Blood (about 2 teaspoons) will be drawn for routine tests.
- If you have not had them done in the last month, you will have scans to check the status of the disease. This will include a chest x-ray, computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, and/or a positron emission tomography (PET) scan. If the study doctor thinks it is more appropriate for you, other types of scans may need to be performed. The study doctor will discuss these scans with you, and you may be asked to sign a separate consent form.
- Females who are able to have children must have a negative blood (about 1 teaspoon) or urine pregnancy test.
Recent studies have found that cetuximab, when given alone or in combination with other chemotherapy drugs, was not effective when given to patients with colorectal cancer that had a KRAS mutation.
For this reason, if you have colorectal cancer:
- Your leftover tumor tissue, if any, will be tested for the KRAS mutation. If you do not have leftover tumor tissue, you will have a needle biopsy of a tumor performed. The tissue will be tested for the KRAS mutation. This procedure will be done on an appropriate tumor area that is able to be biopsied, and it may or may not be the liver tumor. This will be the doctor's decision. To collect a needle biopsy, the affected area is numbed with anesthetic, and a small amount of tumor tissue is withdrawn through a large needle.
- If you have the KRAS mutation, you will not be eligible to receive cetuximab.
The study doctor will discuss the screening test results with you. If the screening tests show that you are not eligible to take part in the study, you will not be enrolled. Other options will be discussed with you.
Study Groups and Dose Levels:
If you are found to be eligible to take part in this study, your doctor will assign you to a study group. Your group will depend on the type of cancer, your KRAS test result (if applicable), and the drugs you have taken in the past.
- If you are in Group 1, you will receive irinotecan and bevacizumab.
- If you are in Group 2, you will receive irinotecan, bevacizumab, and oxaliplatin.
- If you are in Group 3, you will receive irinotecan, bevacizumab, and cetuximab.
The dose that you receive will depend on when you are enrolled in this study and the safety data that is available at that time. The first set of 3-6 participants to join each study group will receive the lowest dose of the drug combination. The next set of 3-6 participants will receive a higher dose of the drug combination. Each new set of participants will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the drug combinations is found.
Once the highest tolerable dose is found for each group, 14 participants with the tumor type that has responded well to a particular study drug combination will receive the study drugs at that dose level. These participants will be in the "expansion" groups.
You will be hospitalized to receive the study drug combination. The morning after you enter the hospital, you will have a catheter placed in your right groin area. A catheter is a sterile flexible tube. It will be placed into a large artery (the blood vessel that carries blood to your liver) while the area is numbed with local anesthetic. Your doctor will explain this procedure to you in more detail, and you will be asked to sign a separate consent form for it.
Once the catheter is in place, you will receive heparin, a drug used to help prevent blood clots. Heparin will be started as soon as the catheter is placed and will continue for up to 2 hours before the infusion of irinotecan is completed.
After you return to your room, you will receive irinotecan as described below.
Study "cycles" will be repeated every 28 days. The catheter will be placed and removed during each cycle. Each time, you will lie in bed for the entire time that the catheter is in place. While the catheter is being removed, the study staff will apply pressure to your groin area for 15 minutes to stop the bleeding.
Study Drug Administration:
Irinotecan will be given through the catheter into your liver artery, continuously for 72 hours (Days 1 through 3 of each cycle). Before every irinotecan dose, you will also receive drugs by vein to lower the risk of nausea, if your doctor thinks this is needed for routine care.
Bevacizumab will be given by vein once every 2 weeks. The first time you receive bevacizumab, it will be given over 90 minutes. If you tolerate it well, all other bevacizumab doses will be given over 30-60 minutes.
Oxaliplatin, if you receive it, will be given by vein over 2 hours once every 2 weeks. Before every oxaliplatin dose, you will also receive drugs by vein to lower the risk of nausea, if your doctor thinks this is needed for routine care.
Cetuximab, if you receive it, will be given by vein once every 2 weeks. The first time you receive cetuximab, it will be given over 2 hours. All other cetuximab doses will be given over 1 hour. You will also receive diphenhydramine by vein before every cetuximab dose in order to lower the risk of side effects.
If you do not tolerate the study drug combination well, the doses that you receive may be lowered. If you experience certain side effects, your study drug doses may be delayed and the study cycle may be longer than 28 days.
You will be in the hospital for about 5-7 days at the beginning of every cycle, until you recover from side effects that may occur. You will be seen by a doctor or "advanced practice" nurse every day while you are in the hospital.
At the beginning of each cycle and then once a week during each cycle, blood (about 1 tablespoon) will be drawn for routine tests. At the beginning of each cycle and then once every 4 weeks (or earlier if needed), you will have a physical exam.
You will have scans such as a chest x-ray, CT, MRI, and/or PET scan after every 2 cycles (8 weeks) or earlier if the study doctor thinks it is in your best interest, or the cancer gets worse. These scans are to check the status of the disease. If the study doctor thinks it is more appropriate for you, other types of scans may need to be performed. The study doctor will discuss these scans with you, and you may be asked to sign a separate consent form.
Additional Tests/Procedures for Some Participants:
If you experience severe diarrhea and/or low white blood cell counts while on this study, blood (about 2 teaspoons) will be drawn to test your DNA to find out if you may be at a higher risk of side effects from irinotecan. If the test shows that you may have a higher risk, then you will receive irinotecan at a lower dose level.
If you are in Group 3 (which as discussed above, does not include colorectal cancer patients with a KRAS mutation), a leftover sample of tumor tissue will be tested for the KRAS mutation. If no leftover tumor tissue from an earlier procedure is available, and if your KRAS status is unknown, you will have a needle biopsy of a tumor performed. The tissue will be tested for the KRAS mutation. This procedure will be done on an appropriate tumor area that is able to be biopsied, and it may or may not be the liver tumor. This will be the doctor's decision.
Length of Study:
You may stay on study for as long as the disease has not gotten worse, the cancer has not gone away completely, and you have not experienced intolerable side effects. In any of those cases, you would be taken off study.
About 28 days after your last dose of study drugs, you will have an end-of-study visit. At this visit, the following tests and procedures may be performed:
- You will have a physical exam, including measurement of your vital signs.
- Your performance status will be recorded.
- Blood (about 2 teaspoons) will be drawn for routine tests.
- If the doctor thinks it is needed, you will have an x-ray, CT scan, PET scan, or MRI scan to check the status of the disease.
- You should not take any herbal drugs during the study.
- You must tell the study doctor about any drugs you may take (prescription or over-the-counter drugs).
- You should tell the study doctor about any changes in how you are feeling and about any health problems you may have during the study.
This is an investigational study. It is investigational to give irinotecan into a liver artery. The study drug combinations and dose levels are also investigational.
The study drugs are commercially available and FDA approved to treat the following:
Irinotecan by vein -- colorectal cancer that is metastatic (has spread). Bevacizumab -- metastatic colorectal cancer, breast cancer, non small-cell lung cancer, and a type of brain cancer called glioblastoma multiforme.
Cetuximab -- colorectal cancer, and head and neck cancer. Oxaliplatin -- colorectal cancer.
Up to 108 patients will take part in this study. All will be enrolled at M. D. Anderson.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Irinotecan, Bevacizumab, Oxaliplatin, Cetuximab
UT MD Anderson Cancer Center
M.D. Anderson Cancer Center
Published on BioPortfolio: 2014-08-27T03:19:12-0400
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Tumors or cancer of the LIVER.
A cancer registry mandated under the National Cancer Act of 1971 to operate and maintain a population-based cancer reporting system, reporting periodically estimates of cancer incidence and mortality in the United States. The Surveillance, Epidemiology, and End Results (SEER) Program is a continuing project of the National Cancer Institute of the National Institutes of Health. Among its goals, in addition to assembling and reporting cancer statistics, are the monitoring of annual cancer incident trends and the promoting of studies designed to identify factors amenable to cancer control interventions. (From National Cancer Institute, NIH Publication No. 91-3074, October 1990)
A 4-hydroxylated metabolite of AFLATOXIN B1, one of the MYCOTOXINS from ASPERGILLUS tainted food. It is associated with LIVER damage and cancer resulting from its P450 activation to the epoxide which alkylates DNA. Toxicity depends on the balance of liver enzymes that activate it (CYTOCHROME P-450) and others that detoxify it (GLUTATHIONE S TRANSFERASE) (Pharmac Ther 50.443 1991). Primates & rat are sensitive while mouse and hamster are tolerant (Canc Res 29.236 1969).
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