Gliadel Wafers & Permanent I-125 Seeds for Glioblastoma
Overview
The purpose of this study is to evaluate the use of combining chemotherapy wafers and radioactive seeds, placed directly into the tumor cavity, to treat glioblastoma multiforme (GBM) tumors.
INTRODUCTION
A brain tumor is a mass of abnormal cells that grow in the brain. Gliomas are the most common type of brain tumor and can be either benign (slow growing) or malignant (fast growing). Tumor aggressiveness is classified by grades I, II, III, or IV. Glioblastoma multiforme (GBM) is a grade IV tumor, which means they are the most aggressive, fast growing, and life-threatening.
Standard treatment for GBM is surgical removal of the tumor mass followed by radiation and/or chemotherapy. Even when it looks like all of the tumor has been removed, microscopic tumor cells—cells too small for the surgeon to see—are almost always left behind. This is why GBM tumors frequently grow back near the original location (called recurrence).
OBJECTIVES OF THE STUDY
The purpose of this research study is to evaluate the use of permanently implanting radioactive I-125 seeds in combination with Gliadel wafers into a brain tumor at the time of surgical removal. I-125 seeds are an approved form of treatment for tumors and have been used in the treatment of glioblastoma after other kinds of treatments have failed. Gliadel wafers are also an approved form of treatment for tumors and have been used in the treatment of glioblastoma. This study investigates a new therapy involving combination therapy of both I-125 seeds and Gliadel wafers to maximize treatment of glioblastoma.
A total of 18 patients will be enrolled in this study at three different sites in the Cincinnati area. Participation in this study will last for approximately 12 months.
PROCEDURES
This protocol involves implanting radioactive “seeds” as well as Gliadel chemotherapy wafers into the area of my brain tumor at the time it is surgically removed, followed by additional radiation and chemotherapy as is commonly given for this type of tumor. Prior to beginning treatment under the guidelines of this protocol, verification of the type of brain tumor will be performed to make sure that it is a glioblastoma multiforme. This may have already been done through a biopsy procedure. Alternatively, biopsy may be performed at the time the tumor is removed. If biopsy should show a tumor other than glioblastoma multiforme, then you will not be eligible for this study, and the appropriate treatment for your tumor will be discussed with you after the tumor is removed. You will undergo an operation that will attempt to remove the entire tumor visible on MRI. During this operation, radioactive I-125 seeds and Gliadel wafers will be placed in the cavity where the tumor was and will be left in place permanently. This is the experimental part of the study. The remainder of the treatment described below is considered standard therapy for GBM tumor.
Approximately 2 weeks after this operation, you will undergo radiation therapy to the brain tumor, which will consist of 6 weeks of treatments, one treatment per day, five days a week.
After completing radiation therapy, you will receive chemotherapy with a drug called Temodar. Temodar is a standard form of chemotherapy for this kind of tumor that can be taken orally.
After completion of radiotherapy, you will be followed by clinical examination and MRI (magnetic resonance imaging) of your brain every 3 months. If the tumor should recur during or after treatment, alternative treatments will be offered to you, which will depend on your exact circumstances. You will participate in the protocol for approximately 1 year, which is the duration of the treatments described above. If there is a big difference in the time period, you will be told.
RISKS
The risks of surgery include blood loss that could require a transfusion, infection, injury to the normal brain, stroke, and seizures. All of these risks are a consequence of the surgery that would be standard treatment of your tumor, regardless of whether or not you participate in this study.
There is a chance that placing the radiation seeds could increase the risk of an infection in the brain after surgery. However, this has not happened in over 30 brain implant cases performed to date by the investigators of this study.
Another risk of placing the radioactive seeds in the tumor includes injury to normal surrounding brain from the radiation (radiation necrosis). This can result in headaches, weakness, seizures, or even alterations in consciousness. Treatments for this include steroids (a medication given to decrease brain swelling), hyperbaric oxygen therapy (a treatment used to decrease brain swelling), or in some instances, a surgical removal of the damaged tissue. In a prior study at the University of Cincinnati, using I-125 seeds for the treatment of GBM, 31 patients were treated with seeds at a dosage that was much higher than the dosage you will receive in this study. In that prior study the rate of radiation necrosis was higher than expected (39%). In this study the dose of I-125 seeds has been cut in half with the hope that this will reduce this risk. Understand that the risk of radiation necrosis is still present.
There is also a possibility that a seed could become dislodged from the tumor and travel through the fluid surrounding it to a different position in the brain. If this should happen it could potentially cause blockage of this fluid requiring surgery to place a “shunt” (a passage way) to bypass the blockage the seed has caused. Dislodging of seeds could also lead to radiation injury to other areas of the brain. At the University of Cincinnati, this complication has been seen infrequently. One patient did develop inflammation of the brain tissue surrounding a dislodged seed resulting in a decrease in vision. The risk of this complication is estimated to be small –probably less than 5%.
Gliadel wafers have been approved for use in patients with your kind of tumor but have not been used in combination with I-125 seeds for patients with your kind of tumor. Potential risks include wound-healing problems and wound infections.
The postoperative external beam radiotherapy being used in this study is considered standard treatment for glioblastoma multiforme. Common side effects include hair loss (always), fatigue, and mild irritation of the scalp. For tumors in some locations, a change in taste, or nausea may occur. You will be informed if these side effects are expected for your treatment.
The Temodar chemotherapy is a commonly used drug for glioblastoma multiforme, and is often considered to be part of the standard treatment for this disease. Possible side effects of the drug include nausea and vomiting, headache, and fatigue. Less common but more potentially severe side effects include lowering some of the blood components making me more susceptible to infections and bleeding. I will be monitored by laboratory tests and medical exams during the study to determine if any of these side effects should occur.
MRI brain scans are the standard used to follow this disease. They are painless procedures and very safe for most patients. You will lie flat in a long metal cylinder during the scan. People who fear closed spaces sometimes find this a little frightening. Patients can be observed at all times by the operators. This way, they can be assisted if necessary. You will be moved out of the machine if requested. The MRI machine makes a thumping sound while operating.
A few patients are at risk for injury from MRI scans. These are people with pacemakers, aneurysm clips (metal clips on the wall of a large artery), or shrapnel fragments. Welders and metal workers are also at risk for injury. This is because of possible metallic foreign bodies in the eye.
There are also risks and discomforts that may occur which are not yet known.
Benefits
The benefits of participating in this study may be the possibility of destroying the tumor more effectively and thereby increasing the time that you survive this tumor as well as possibly improving and maintaining your quality of life.
Alternative Procedures
If you choose not to participate in this study, then standard treatment for your tumor would include surgical resection followed by 6 weeks of radiation therapy and postoperative chemotherapy as described above. Additionally, other investigational treatments for your kind of tumor may be available.
Location & contact
Christopher McPherson, MD (Principal investigator)
Ronald Warnick MD, John Breneman, MD, Margie Gerena Lewis, MD (Co-investigators)
Suzanne Kempisty, RN (Study coordinator)
Email: suzanne.kempisty-cliver@uc.edu
Good Samaritan Hospital
375 Dixmyth Avenue
Cincinnati, OH 45220-2489
Telephone: 513-558-5398
Fax: 513-558-7702
More information
Study design: Phase I, Prospective
Start date: 12/2005
Close date: upon enrollment of 18 patients
Sponsor: Synthes, Inc.
Study ID number: IRB#:05109-1005
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